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Distinct extended amygdala circuits for divergent motivational states
Open accessAbstract
The co-morbidity of anxiety and dysfunctional reward processing in illnesses such as addiction and depression suggests that common neural circuitry contributes to these disparate neuropsychiatric symptoms. The extended amygdala, including the bed nucleus of the stria terminalis (BNST), modulates fear and anxiety, but also projects to the ventral tegmental area (VTA), a region implicated in reward and aversion, thus providing a candidate neural substrate for integrating diverse emotional states. However, the precise functional connectivity between distinct BNST projection neurons and their postsynaptic targets in the VTA, as well as the role of this circuit in controlling motivational states, have not been described. Here we record and manipulate the activity of genetically and neurochemically identified VTA-projecting BNST neurons in freely behaving mice. Collectively, aversive stimuli exposure produced heterogeneous firing patterns in VTA-projecting BNST neurons. By contrast, in vivo optically identified glutamatergic projection neurons displayed a net enhancement of activity to aversive stimuli, whereas the firing rate of identified GABAergic (γ-aminobutyric acid-containing) projection neurons was suppressed. Channelrhodopsin-2-assisted circuit mapping revealed that both BNST glutamatergic and GABAergic projections preferentially innervate postsynaptic non-dopaminergic VTA neurons, thus providing a mechanistic framework for in vivo circuit perturbations. In vivo photostimulation of BNST glutamatergic projections resulted in aversive and anxiogenic behavioural phenotypes. Conversely, activation of BNST GABAergic projections produced rewarding and anxiolytic phenotypes, which were also recapitulated by direct inhibition of VTA GABAergic neurons. These data demonstrate that functionally opposing BNST to VTA circuits regulate rewarding and aversive motivational states, and may serve as a crucial circuit node for bidirectionally normalizing maladaptive behaviours.
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Written from the paper’s full text.
TL;DR
In mice, VTA-projecting BNST neurons comprise opposing glutamatergic and GABAergic subcircuits: aversive stimuli increase glutamatergic activity and suppress GABAergic activity, and optogenetic activation of these pathways produces aversive/anxiogenic versus rewarding/anxiolytic states, respectively. These findings identify a bidirectional BNST→VTA circuit node for motivational and emotional processing.
Key findings
- In vivo antidromic identification found 53/137 BNSTv→VTA projection neurons; aversive stimuli produced heterogeneous firing patterns across these neurons. Identified Vglut2BNSTv→VTA neurons (34/145) showed net enhanced firing during aversive events and shock-associated cues, whereas VgatBNSTv→VTA neurons (33/77) were principally suppressed.
- Circuit mapping showed that Vglut2BNSTv→VTA and VgatBNSTv→VTA terminals formed functional synapses primarily onto non-dopaminergic and medially located dopaminergic VTA neurons.
- Photostimulation of Vglut2BNSTv→VTA produced avoidance of a stimulation-paired chamber, reduced active reward seeking, and anxiety-like open-field behavior; the aversive phenotype was abolished by intra-VTA ionotropic glutamate receptor antagonists.
- Photostimulation of VgatBNSTv→VTA produced place preference, supported optical self-stimulation, and increased open-arm time in the elevated plus maze; these effects were prevented by an intra-VTA GABAA antagonist and recapitulated by direct inhibition of VTA GABAergic neurons. Concurrent VgatBNSTv→VTA stimulation during foot shock reduced freezing and increased later open-arm time/entries.
Methods
- Adult male C57BL/6J, Vgat-ires-cre, and Vglut2-ires-cre mice received stereotactic viral injections (ChR2-eYFP, NpHR) and optical fibers/MEA implants; experiments included anesthetized and behaving in vivo electrophysiology, patch-clamp recordings in VTA slices, unpredictable foot-shock sessions, and optogenetic behavioral assays.
- In vivo electrophysiology used a 16-channel MEA in BNSTv and optical fibers above VTA for antidromic identification; units were classified using spike latency, waveform correlation, and z-score firing changes during foot-shock sessions.
- Behavioral assays included real-time place preference, open field, sucrose self-administration, optical self-stimulation/self-inhibition, elevated plus maze, and foot-shock-induced freezing, with intra-VTA antagonist microinfusions in some experiments.
Limitations
- The paper states that shock artifacts prevented reliable quantification of neuronal firing 500–1000 ms after foot-shock onset, excluding approximately 0.8–1.66% of collected data during the foot-shock session.
- Evident from the text: all experiments used adult male mice, so sex differences and generalization to females are not addressed.
- Evident from the text: the paper does not include a dedicated limitations section; circuit specificity relies on viral targeting, optogenetic manipulation, slice physiology, and pharmacological blockade rather than fully selective circuit-silencing approaches.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in vivo optically-identified glutamatergic projection neurons displayed a net enhancement of activity to aversive stimuli”
- Also stated in: § Abstract · plain
“Collectively, exposure to the aversive event or associated cues alone enhanced the firing of Vglut2BNSTv→VTA neurons”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, aversive stimuli exposure produced heterogeneous firing patterns in VTA-projecting BNST neurons.”
- Also stated in: § Abstract · boosted
“Identified BNSTv→VTA neurons segregated into three functionally distinct classes based on changes in their normalized firing rates throughout the foot-shock session (Supplementary Fig. 3), demonstrating that BNSTv→VTA neurons differentially encode information related to aversive stimuli and their associated contextual cues.”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas the firing rate of identified GABAergic projection neurons was suppressed”
- Also stated in: § Abstract · plain
“while simultaneously suppressing the activity of VgatBNSTv→VTA neurons.”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“activation of BNST GABAergic projections produced rewarding and anxiolytic phenotypes”
- Also stated in: § Abstract · hedged
“Photostimulation of the VgatBNSTv→VTA pathway and direct inhibition of VgatVTA neurons significantly increased time spent in the open arms of an elevated plus maze, indicative of anxiolysis”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“VgatBNSTv→VTA::ChR2 mice spent significantly less time frozen (Fig. 5h)”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“as well as significantly more open-arm time and entries in the elevated-plus maze relative to controls (Supplementary Fig. 18)”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In vivo photostimulation of BNST glutamatergic projections resulted in aversive and anxiogenic behavioral phenotypes.”
- Also stated in: § Abstract · hedged
“inescapable activation of this pathway for 20 min in an open field resulted in significantly less center- and more corner-time in Vglut2BNSTv→VTA::ChR2 mice in the 10 min following stimulation offset compared to controls”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“VTA infusions of a GABAA receptor antagonist prevented the VgatBNSTv→VTA mediated place preference compared to saline injections”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Vglut2BNSTv→VTA and VgatBNSTv→VTA terminals formed functional synapses primarily onto non-dopaminergic and medially located dopaminergic neurons”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“activation of BNST GABAergic projections produced rewarding and anxiolytic phenotypes”
- Also stated in: § Abstract · plain
“20 Hz photostimulation in VgatBNSTv→VTA::ChR2 mice resulted in a significant place preference”
- Also stated in: § Abstract · plain
“VgatBNSTv→VTA::ChR2 mice readily nose poked to receive photostimulation”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · plain
- It may state two separate claims as one. 9
- Probably not a substantial claim. 19
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“photostimulation of the CaMKIIaBNSTv→VTA pathway produced both glutamatergic and γ-aminobutyric acid (GABAergic) currents in VTA neurons (Supplementary Fig. 4), demonstrating that neurochemically distinct BNSTv neurons project to the VTA.”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“photostimulation of ChR2-containing fibers originating from Vglut2 (Vglut2BNSTv→VTA::ChR2) or Vgat (VgatBNSTv→VTA::ChR2) expressing BNSTv neurons produced excitatory or inhibitory postsynaptic currents respectively”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, data collected during these time epochs were excluded from analysis.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“into the VTA in a counter balanced design (all drugs from Tocris).”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > Intra-VTA injection of antagonists and photostimulation of Vglut2BNSTv→VTA::ChR2 and VgatBNSTv→VTA::ChR2 projections during real-time place preference
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results show that reward-related responses to VgatBNSTv→VTA activation are recapitulated by directly inhibiting VgatVTA neurons, thus providing a circuit mechanism for the VgatBNSTv→VTA pathway to regulate motivated behavior.”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Briefly, discrimination of individual units was performed offline using principal component analysis to separate individual units from the same electrode. In addition, auto- and cross-correlograms, firing characteristics, and inter-spike interval distributions were examined to ensure units were well-isolated.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Placements of recording electrode tips within the BNSTv and optical fibers within the VTA were verified with histological examination of brain tissue following the experiments.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo anesthetized electrophysiology
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This represents an approximate loss of 0.8 – 1.66% of the collected data during the foot-shock session.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“During the time epoch surrounding the individual delivered foot shocks, large shock artifact were readily apparent.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Resulting data was binned in 30 s epochs in order to minimize the skewing of our results due to data lost by the shock artifacts.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Electrical stimulation of the BNST produces both excitatory and inhibitory responses in VTA neurons in vivo6 implying that distinct subcircuits may exist.”
§ Distinct extended amygdala circuits for divergent motivational states > Abstract
What the sources say
- Not checked yetcites [6] Georges, F. & Aston-Jones, G. Potent regulation of midbrain dopamine neurons by the bed nucleus of the stria terminalis. J. Neurosci. 21, RC160 (2001) source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“BNSTv neurons were classified as antidromic-responsive, if the following 3 criteria were met: 1) stable antidromic spike latency (< 0.2 ms), 2) ability to respond reliably to high frequency photostimulation, 3) collision between orthodromic- and antidromic-evoked spikes.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo anesthetized electrophysiology
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Neuronal units were included in the data if the signal-to-noise ratio was high, and the mean firing rate was between 0.5 – 25 Hz during baseline recording periods.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Mice had 2 days off between each VTA microinjection.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > Intra-VTA injection of antagonists and photostimulation of Vglut2BNSTv→VTA::ChR2 and VgatBNSTv→VTA::ChR2 projections during real-time place preference
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, recording sites was verified histologically using electrolytic lesions at 200 µA for 5 s.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“neuronal firing responses in the 500 – 1000 ms following foot shock onset could not be reliably quantified”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All mice were infused at a rate of 0.1 µl per minute. The injector remained in place for approximately 2 min following infusion to ensure proper diffusion of drug into the VTA.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > Intra-VTA injection of antagonists and photostimulation of Vglut2BNSTv→VTA::ChR2 and VgatBNSTv→VTA::ChR2 projections during real-time place preference
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Recorded BNSTv units were classified as light-responsive, and thus VTA-projecting, if they met both of the following two criteria. 1) The latency of the first spike after light stimulation onset was less than 20 ms for ≥ 20% of the trials. 2) Light-evoked and spontaneous waveform shapes had a correlation coefficient of > 0.90.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Neural activity was recorded from the same mice during the cue exposure, foot shock, and cue re-exposure sessions, therefore we were able to reliably record activity from the same population of neurons during each of the three sessions.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, timestamp data to signify the start and end of foot-shock sessions, and the delivery of light pulses to optical fibers was synchronized with electrophysiological data.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Following the 1 day 20 Hz training session, mice were run daily at each photostimulation frequency (1, 5, 10, 20, 40 Hz) in a counter-balanced design.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > Optical self-stimulation of VgatBNSTv→VTA::ChR2 projections
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“While these were easily isolated and excluded from the analyzed waveform data using offline spike sorting”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo electrophysiology
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The injector needle (33 gauge steel tube, McMasters-Carr) extended approximately 1 mm past the cannula to ensure drug delivery 0.5 mm below the optical fiber.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > Intra-VTA injection of antagonists and photostimulation of Vglut2BNSTv→VTA::ChR2 and VgatBNSTv→VTA::ChR2 projections during real-time place preference
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Once stable nose-poking behavior for 15% sucrose was observed (approx. 100 active nose pokes on at least 2 consecutive days), all mice received constant 20 Hz photostimulation during the entire 30 min sucrose session.”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > Photostimulation of Vglut2BNSTv→VTA::ChR2 projections during sucrose self-administration
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“This is supported by optogenetic studies showing the projection-specific effects of BNST neurons on behavior (87–90).”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [89]
In the citing paper
“Moreover, individual subregions of the BNST have been shown to differentially regulate separable features of the anxiety phenotype31,85 (Fig. 3).”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [85]
In the citing paper
“activity in glutamatergic ventral BNST neurons projecting to the VTA produces anxiety-like behaviors, whereas GABAergic neurons in the ventral BNST exert anxiolysis via a parallel pathway85.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [85]
In the citing paper
“It has recently been shown that the BNST contains distinct anxiogenic and anxiolytic GABAergic neuronal subsets with unique patterns of long-range connections (Jennings et al., 2013; Kim et al., 2013).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Jennings et al., 2013
In the citing paper
“Our results provide further evidence of the importance of long-range GABAergic projection neurons in the control of anxiety (Jennings et al., 2013; Kim et al., 2013).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Jennings et al., 2013
In the citing paper
“In contrast, photostimulation of glutamatergic projections from ventral BNST to the ventral tegmental area (VTA) (Jennings et al., 2013) was sufficient to induce a persistent elevation in anxiety.”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Jennings et al., 2013
In the citing paper
“Notably, BNST neurons have been shown to inhibit dopamine neurons involved in conventional reward processing by activating local GABAergic neurons63–65, suggesting that anxiety-related circuits may interfere with appetitive learning and behavior.”
From Dopamine dynamics as a regulatory mechanism for shifting between defensive and reward-seeking behaviors (2026) · cites this paper as [63]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Recording electrode differs from the stated requirement for all in vivo experiments
MinorThe methods say mice in all in vivo electrophysiology experiments received a 16-wire array, whereas the anesthetized in vivo electrophysiology procedure describes recording with a glass electrode.
“For all in vivo electrophysiology experiments, mice were implanted with a 16-wire (4 × 4 configuration, wire diameter∼30µm) tungsten multielectrode array (MEA)”
“Extracellular neural activity was recorded using a glass recording electrode (5 − 10 MΩ: and filled with 0.5 M NaCl).”
Injection laterality differs for an in vivo electrophysiology experiment
MinorThe methods say all in vivo electrophysiology mice received unilateral BNSTv injections, but the anesthetized in vivo electrophysiology procedure specifies bilateral injections.
“For all in vivo electrophysiology experiments, male mice were unilaterally injected with 0.5 µl of purified and concentrated adeno-associated virus (AAV)”
“C57BL/6J mice were bilaterally injected with 0.3 µl of AAV5-CaMKIIa-ChR2-eYFP into the BNSTv.”
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“Recorded vBNST units were classified as light-responsive, and thus VTA-projecting, if they met both of the following two criteria: (1) the latency of the first spike after light stimulation onset was less than 20ms for$20% of the trials; and (2) light-evoked and spontaneous waveform shapes had a correlation coefficien…”
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Vong, L., Ye, C., Yang, Z., Choi, B. J., Chua, S. C., & Lowell, B. B. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.028 · Cited by 1,237
Dopamine neurons modulate neural encoding and expression of depression-related behaviour
Tye, K. M., Mirzabekov, J. J., Warden, M. R., Ferenczi, E. A., Tsai, H.-C., Finkelstein, J., Kim, S.-Y., Adhikari, A., Thompson, K. R., Andalman, A. S., et al. (2013) · Nature · doi:10.1038/nature11740 · Cited by 1,073
Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking
Stuber, G. D., Sparta, D. R., Stamatakis, A. M., van Leeuwen, W. A., Hardjoprajitno, J. E., Cho, S., Tye, K. M., Kempadoo, K. A., Zhang, F., Deisseroth, K., et al. (2011) · Nature · doi:10.1038/nature10194 · Cited by 878
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Encoding innately recognized odors via a generalized population code
Qiu, Q., Wu, Y., Ma, L., & Yu, C. R. (2021) · Current Biology · doi:10.1016/j.cub.2021.01.094 · Cited by 34
“Photo-stimulation of glutamatergic projection from BNST to the ventral tegmental area (VTA) triggers avoidance.(63) We, therefore, decided to survey the activation of these brain areas in response to innately recognized odors.”
Huang, S., Wu, K., Guo, M., Shao, S., Hua, R., & Zhang, Y. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01678-1 · Cited by 33
“Usually, glutamatergic and GABAergic neurons in the ventral BNST differ in their physiological properties and exert functionally opposing effects in neural circuits to regulate emotion and motivation [41, 42].”
BackgroundAllopregnanolone in the bed nucleus of the stria terminalis modulates contextual fear in rats
Nagaya, N., Acca, G. M., & Maren, S. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00205 · Cited by 32
“Moreover, recent optogenetic approaches have shown that discrete neural circuits within the BNST are involved in regulating responses to aversive contexts (Jennings et al., 2013; Kim et al., 2013).”
BackgroundKing, S. B., Lezak, K. R., O’Reilly, M. L., Toufexis, D. J., Falls, W. A., Braas, K. M., May, V., & Hammack, S. E. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.16 · Cited by 33
Jiang, J., Liu, H., Huang, Z., Cui, Y., Zhang, X., Zhang, X., Cui, Y., & Xin, W. (2016) · Addiction Biology · doi:10.1111/adb.12468 · Cited by 33
“For example, it was reported that activation of VTA-projecting amygdala neurons directly suppressed the firing rate of GABAergic neurons in VTA and participated in the reward-related behavior (Jennings et al. 2013).”
BackgroundA prefrontal-bed nucleus of the stria terminalis circuit limits fear to uncertain threat
Glover, L. R., McFadden, K. M., Bjorni, M., Smith, S. R., Rovero, N. G., Oreizi-Esfahani, S., Yoshida, T., Postle, A. F., Nonaka, M., Halladay, L. R., et al. (2020) · eLife · doi:10.7554/elife.60812 · Cited by 35
“, 2020), diffuse (e.g., contextual; Sullivan et al., 2004; Kalin et al., 2005; Duvarci et al., 2009; Davis et al., 2010; Luyten et al., 2012; Jennings et al., 2013; c.f. Haufler et al., 2013), or temporally ambiguous (e.”
BackgroundMarvar, P. J., Andero, R., Hurlemann, R., Lago, T. R., Zelikowsky, M., & Dabrowska, J. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.1647-20.2020 · Cited by 29
“Both the CeA and the BNST receive afferent glutamatergic information from the BLA among many other regions (Jennings et al., 2013; Torrisi et al., 2018) (Fig.”
BackgroundShen, L., Zhang, G., Tao, C., Seo, M. B., Zhang, N. K., Huang, J., Zhang, L. I., & Tao, H. W. (2022) · Nature Communications · doi:10.1038/s41467-022-28854-z · Cited by 33
Tian, G., Hui, M., Macchia, D., Derdeyn, P., Rogers, A., Hubbard, E., Liu, C., Vasquez, J. J., Taniguchi, L., Bartas, K., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110775 · Cited by 31
“Glutamatergic and GABAergic BNST cells project to the ventral midbrain, although the majority of those synapsing onto VTA cells are believed to be GABAergic (Dong and Swanson, 2004, 2006a, 2006b; Georges and Aston-Jones, 2001, 2002; Jalabert et al., 2009; Jennings et al., 2013; Kudo et al., 2012).”
InfluentialSuthard, R. L., Jellinger, A. L., Surets, M., Shpokayte, M., Pyo, A. Y., Buzharsky, M. D., Senne, R. A., Dorst, K. E., Leblanc, H., & Ramirez, S. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.01.007 · Cited by 35
Goal-Driven Cognition in the Brain: A Computational FrameworkPreprint
O’Reilly, R. C., Hazy, T. E., Mollick, J., Mackie, P., & Herd, S. A. (2014) · arXiv (Cornell University) · doi:10.48550/arxiv.1404.7591 · Cited by 54
Protracted maturation of forebrain afferent connections of the ventral tegmental area in the rat
Yetnikoff, L., Reichard, R. A., Schwartz, Z. M., Parsely, K. P., & Zahm, D. S. (2014) · Journal of Comparative Neurology · doi:10.1002/cne.23459 · Cited by 30
“…exert cooperative and competing influences to regulate the activity of VTA dopamine neurons and behavior (Grace et al., 2007; Lammel et al., 2012; Jen- nings et al., 2013) by targeting dopamine neurons directly or indirectly via local interneurons (Carr and Sesack, 2000; Sesack and Carr,…”
BackgroundDaldrup, T., Lesting, J., Meuth, P., Seidenbecher, T., & Pape, H. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.03.020 · Cited by 33
Vahid-Ansari, F., & Albert, P. R. (2017) · Neurotherapeutics · doi:10.1007/s13311-017-0590-3 · Cited by 32
Urien, L., Stein, N. P., Ryckman, A., Bell, L., & Bauer, E. P. (2021) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2021.107401 · Cited by 30
“By examining the interactions between the BNST and its outputs, we can unravel the distinct functions of BNST subnuclei (Jennings et al., 2013).”
BackgroundOzawa, A., & Arakawa, H. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113234 · Cited by 29
Parise, E. M., Parise, L. F., Sial, O. K., Cardona-Acosta, A. M., Gyles, T. M., Juarez, B., Chaudhury, D., Han, M., Nestler, E. J., & Bolaños‐Guzmán, C. A. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.05.002 · Cited by 31
Asim, M., Wang, H., Chen, X., & He, J. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14422 · Cited by 29
“56,57 These results offer strong proof that the activity of BLA CAMKII neurons can encode extremely negative valence, and may thus lead to relentless fear and a depressive state.”
BackgroundMethodNPY Y2 receptors in the central amygdala reduce cued but not contextual fear
Verma, D., Wood, J. C., Lach, G., Mietzsch, M., Weger, S., Heilbronn, R., Herzog, H., Bonaventure, P., Sperk, G., & Tasan, R. O. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.08.038 · Cited by 35
“, 2001) is involved in the mediation of anxiolytic-like behavior (Gungor and Pare, 2014; Jennings et al., 2013; Sink et al., 2011).”
Takahashi, D., Asaoka, Y., Kimura, K., Hara, R., Arakaki, S., Sakasai, K., Suzuki, H., Yamauchi, N., Nomura, H., Amano, T., et al. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.3047-18.2019 · Cited by 30
“…optogenetic studies showing that photoactivation of VTA-projecting BNST neurons induces reward-related behaviors in a real-time place preference test (Jennings et al., 2013; Kim et al., 2013), which suggests that VTA-projecting BNST neurons positively regulate the mesolimbic reward circuit.”
BackgroundMatsushita, N., Muroi, Y., Kinoshita, K.-I., & Ishii, T. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.02.003 · Cited by 29
Donner, N. C., Davies, S. M., Fitz, S. D., Kienzle, D. M., Shekhar, A., & Lowry, C. A. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109730 · Cited by 28
“Other studies have shown that activation of glutamatergic neurons within the ventral BNST (BSTLV) projecting to the ventral tegmental nucleus increase anxiety-like defensive behavioral responses, whereas activation of GABAergic neurons within the ventral BNST projecting to the ventral tegmental nucleus decrease anxiet…”
BackgroundMedina, L. M., Abellán, A., Vicario, A., Castro‐Robles, B., & Desfilis, E. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804042-3.00019-1 · Cited by 32
Girven, K. S., Aroni, S., Navarrete, J. S., Marino, R. A. M., McKeon, P. N., Cheer, J. F., & Sparta, D. R. (2020) · Addiction Biology · doi:10.1111/adb.12961 · Cited by 28
Self-citationKim, S.-R., & Kim, S. (2021) · Molecules and Cells · doi:10.14348/molcells.2021.0006 · Cited by 29
“…place avoidance (i.e., mice avoided the chamber associated with the optogenetic stimulation of this pathway) and anxiety-like behavior, whereas analogous terminal stimulation of vBNSTVgat neurons in the VTA supported place preference and reduced anxiety-like behavior (Jennings et al., 2013b).”
BackgroundMethodResultInfluentialRepurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success?
Carboni, E., Carta, A. R., Carboni, E., & Novelli, A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.657714 · Cited by 33
Threat and Reward Imminence Processing in the Human Brain
Murty, D. V. P. S., Song, S., Surampudi, S. G., & Pessoa, L. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.1778-22.2023 · Cited by 33
“These results are consistent with the involvement of the BST in reward-and arousal-related processing in rodents (Jennings et al., 2013; Rodriguez-Romaguera et al., 2020), but previously not observed in the human literature, as far as we are aware.”
ResultOverview on Research and Clinical Applications of Optogenetics
Towne, C. L., & Thompson, K. R. (2016) · Current Protocols in Pharmacology · doi:10.1002/cpph.13 · Cited by 29
“Additional circuitry implicated in feeding are the inhibitory projections from the BNST to the LH (Jennings et al., 2013b) and the calcitonin gene-related peptide-expressing neurons of the parabrachial nucleus that project to the amygdala to powerfully suppress feeding (Carter et al.”
BackgroundAlbrechet‐Souza, L., Viola, T. W., Grassi‐Oliveira, R., Miczek, K. A., & de Almeida, R. M. M. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00762 · Cited by 29
“Stress can differentially affect these circuitries within the BNST to shift the balance from an anxiolytic to an anxiogenic state (Jennings et al., 2013; Kim et al., 2013; Daniel and Rainnie, 2016; Henckens et al., 2016).”
BackgroundCerebellar Prediction and Feeding Behaviour
Iosif, C. I., Bashir, Z. I., Apps, R., & Pickford, J. (2022) · The Cerebellum · doi:10.1007/s12311-022-01476-3 · Cited by 28
“LH neurons also integrate information from the ventral tegmental area (VTA) and nucleus accumbens (NAc), which are involved in processing food and reward-related cues [105, 106, 107, 108].”
Cook, J. B., Werner, D. F., Maldonado‐Devincci, A. M., Leonard, M. N., Fisher, K. R., O’Buckley, T. K., Porcu, P., McCown, T. J., Besheer, J., Hodge, C. W., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4733-13.2014 · Cited by 29
“Optical stimulation of these projections produce opposing effects on reward and aversion (Jennings et al., 2013), with stimulation of the GABAergic projection producing reward and stimulation of the glutamatergic projection producing aversive behavior.”
BackgroundNew approaches to manipulating the epigenome
Day, J. J. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/jday · Cited by 27
Pleil, K. E., & Skelly, M. J. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.01.007 · Cited by 29
“CRFergic projections from the BNST to the VTA drive reward-seeking behaviors (Jennings et al., 2013; Pina et al., 2015; Rinker et al., 2016), likely by disinhibiting DA neurons.”
BackgroundSelf-citationCampbell, R. R., Domingo, R. D., Williams, A. R., Wroten, M. G., McGregor, H. A., Waltermire, R. S., Greentree, D. I., Goulding, S. P., Thompson, A. B., Lee, K. M., et al. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1909-18.2018 · Cited by 27
“Stimulation of both GABAergic and glutamatergic efferents from the BNST excite VTA neurons (Georges and Aston-Jones, 2001; Jennings et al., 2013) to drive drug/alcohol-conditioned reward and drug/alcohol-seeking behavior (Sartor and Aston-Jones, 2012; Jennings et al.”
BackgroundInfluentialScheimann, J. R., Moloney, R. D., Mahbod, P., Morano, R. L., Fitzgerald, M. E., Hoskins, O., Packard, B. A., Cotella, E. M., Hu, Y., & Herman, J. P. (2019) · eLife · doi:10.7554/elife.44672 · Cited by 31
Biomarkers of the Endocannabinoid System in Substance Use Disorders
Navarrete, F., García‐Gutiérrez, M. S., Gasparyan, A., Navarro, D., Lopez‐Picon, F. R., Morcuende, Á., Femenía, T., & Manzanares, J. (2022) · Biomolecules · doi:10.3390/biom12030396 · Cited by 26
“Repeated drug exposure causes adaptive changes in the circuitry of the extended amygdala, resulting in enhanced reactivity to stress [11] and the emergence of negative emotions [12].”
BackgroundDu, Y.-L., Zhou, S., Ma, C., Chen, H., Du, A., Deng, G., Liu, Y., Tose, A. J., Sun, L., Liu, Y., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.06.021 · Cited by 27
Toward a systems-oriented approach to the role of the extended amygdala in adaptive responding
Waraczynski, M. A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.015 · Cited by 28
Anxiety disorders: Treatments, models, and circuitry mechanisms
Ren, L., Fan, Y., Wu, W., Qian, Y., He, M., Li, X., Wang, Y., Yang, Y., Wen, X., Zhang, R., et al. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176994 · Cited by 35
Goode, T. D., Kim, J., & Maren, S. (2015) · eNeuro · doi:10.1523/eneuro.0037-15.2015 · Cited by 28
“Jennings et al. (2013) demonstrated that photostimulation of glutamatergic projections of the ventral BNST to the ventral tegmental area (VTA) produced increases in anxiety, whereas photostimulation of GABAergic BNST projections to the VTA was anxiolytic.”
BackgroundDong, X., Li, S., & Kirouac, G. J. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100266 · Cited by 29
“The BSTDL and CeL have been shown to be involved in fear and anxiety (Walker et al., 2003, 2009; Kalin et al., 2004; Cai et al., 2012; Jennings et al., 2013; Kim et al., 2013; Ventura-Silva et al., 2013; Pleil et al., 2015; Ahrens et al., 2018; Asok et al., 2018; Normandeau et al., 2018).”
BackgroundGastelum, C., Perez, L., Hernandez, J., Le, N., Vahrson, I., Sayers, S., & Wagner, E. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052728 · Cited by 27
“On the other hand, activation of VTA GABAergic neurons promotes aversive responses, while their inhibition promotes reward, by dampening or promoting A 10 dopamine signaling, respectively [72,73].”
Roles of the bed nucleus of the stria terminalis and amygdala in fear reactions
Hulsman, A. M., Terburg, D., Roelofs, K., & Klumpers, F. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819975-6.00027-3 · Cited by 29
Dynamics of coupled mode solitons in bursting neural networks
Nfor, N. O., Ghomsi, P. G., & Kakmeni, F. M. M. (2018) · Physical review. E · doi:10.1103/physreve.97.022214 · Cited by 26
Distinct Encoding of Reward and Aversion by Peptidergic BNST Inputs to the VTA
Soden, M. E., Yee, J. X., Cuevas, B., Rastani, A., Elum, J. E., & Zweifel, L. S. (2022) · Frontiers in Neural Circuits · doi:10.3389/fncir.2022.918839 · Cited by 25
“In contrast, stimulation of GABA neurons in the BNST is anxiolytic (Jennings et al., 2013).”
BackgroundInfluentialCorticotropin releasing hormone and imaging, rethinking the stress axis
Contoreggi, C. S. (2014) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2014.11.008 · Cited by 26
“Seemingly disparate disorders share network and structural connectivity but they lack specificity; making clinical utilization of these functional technologies nonspecific at this point in their development [20, 27, 28, 29].”
BackgroundOptical suppression of drug-evoked phasic dopamine release
McCutcheon, J. E., Cone, J. J., Sinon, C. G., Fortin, S. M., Kantak, P. A., Witten, I. B., Deisseroth, K. A., Stuber, G. D., & Roitman, M. F. (2014) · Frontiers in Neural Circuits · doi:10.3389/fncir.2014.00114 · Cited by 27
Self-citationCappon, D., Ludwiczak, A., Lagrata, S., Miller, S., Akram, H., Hyam, J., Zrinzo, L. U., Matharu, M. S., & Jahanshahi, M. (2019) · Cephalalgia · doi:10.1177/0333102419839957 · Cited by 25
A subcortical switchboard for perseverative, exploratory and disengaged states
Ahmadlou, M., Shirazi, M. Y., Zhang, P., Rogers, I. L. M., Dziubek, J., Young, M., & Hofer, S. B. (2025) · Nature · doi:10.1038/s41586-025-08672-1 · Cited by 25
“We used a self-stimulation test that is commonly used to assess the valence of a neural manipulation 31,32 , in which mice are presented with two nose-poke ports, only one of which triggers optogenetic self-stimulation upon entering (opto-linked port; Fig.”
Interconnected neural circuits mediating social reward
Isaac, J., & Murugan, M. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2024.10.004 · Cited by 26
Trujillo‐Pisanty, I., Conover, K. L., & Shizgal, P. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3328-x · Cited by 24
“The values shown are expressed as within-session deviations from vehicle means and are averaged across subject.”
BackgroundA circuit of COCH neurons encodes social-stress-induced anxiety via MTF1 activation of Cacna1h
Jing, W., Zhang, T., Liu, J., Huang, X., Yu, Q., Yu, H., Zhang, Q., Li, H., Deng, M., Zhu, L., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110177 · Cited by 25
The neural computation of human prosocial choices in complex motivational states
Saulin, A., Horn, U., Lotze, M., Kaiser, J., & Hein, G. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118827 · Cited by 25
Sex differences in VTA GABA transmission and plasticity during opioid withdrawal
Kalamarides, D. J., Singh, A., Wolfman, S. L., & Dani, J. A. (2023) · Scientific Reports · doi:10.1038/s41598-023-35673-9 · Cited by 24
Deciphering Memory Function with Optogenetics
Beyeler, A., Eckhardt, C. A., & Tye, K. M. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-420170-5.00012-x · Cited by 24
“vBNST to the VTA, primarily to nondopaminergic neurons, and targeted ChR2 to these neurons using the Vglut2::Cre and Vgat::Cre mouse lines, respectively.(83) Whereas all neurons displayed heterogeneous firing activity 360 Anna Beyeler et al.”
BackgroundMethodInfluentialAltered responsiveness of BNST and amygdala neurons in trauma-induced anxiety
Rodríguez-Sierra, O. E., Goswami, S., Turesson, H., & Paré, D. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.128 · Cited by 25
Electrical stimulation of the bed nucleus of the stria terminalis reduces anxiety in a rat model
Luyck, K., Tambuyzer, T., Deprez, M., Rangarajan, J. R., Nuttin, B., & Luyten, L. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.2 · Cited by 24
Simmons, D. V., Petko, A. K., & Paladini, C. A. (2017) · Journal of Neurophysiology · doi:10.1152/jn.00270.2017 · Cited by 23
“The bed nucleus of stria terminalis (BNST), for example, sends both glutamatergic and GABAergic projections to VTA neurons, in vivo stimulation of which produces aversive/anxiogenic and rewarding/anxiolytic behavioral phenotypes, respectively (Jennings et al. 2013).”
BackgroundBulik, C. M. (2015) · Nordic Journal of Psychiatry · doi:10.3109/08039488.2015.1074284 · Cited by 27
Migraine and Reward System—Or Is It Aversive?
Cahill, C. M., Cook, C. P., & Pickens, S. R. (2014) · Current Pain and Headache Reports · doi:10.1007/s11916-014-0410-y · Cited by 25
Maita, I., Bazer, A. S., Blackford, J. U., & Samuels, B. A. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819975-6.00026-1 · Cited by 23
Optogenetic fMRI for Brain-Wide Circuit Analysis of Sensory Processing
Lee, J.-Y., You, T., Woo, C., & Kim, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012268 · Cited by 22
“The optogenetic approach to activating axon terminals can trigger antidromic propagation from axon to soma in addition to postsynaptic activation induced by synaptic transmission (Figure 2A) [21,22].”
BackgroundBiphasic effects of anandamide on behavioural responses
Rodrı́guez–Manzo, G., & Canseco-Alba, A. (2015) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000154 · Cited by 23
“connections with the bed nucleus of the stria terminalis, a part of the so-called extended amygdala (Jennings et al., 2013).”
BackgroundUse of Adeno‐Associated and Herpes Simplex Viral Vectors for In Vivo Neuronal Expression in Mice
Penrod, R. D., Wells, A. M., Carlezon, W. A., & Cowan, C. W. (2015) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0437s73 · Cited by 22
Harris, N. A., & Winder, D. G. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00169 · Cited by 22
The role of the bed nucleus of the stria terminalis in pain-induced aversive motivation
Minami, M. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.10.003 · Cited by 25
Ch’ng, S. S., Fu, J., Brown, R. M., Smith, C. M., Hossain, M. A., McDougall, S. J., & Lawrence, A. J. (2019) · The Journal of Comparative Neurology · doi:10.1002/cne.24695 · Cited by 23
“…(VTA); however, these pathways show divergent but complementary roles in drug consumption, conditioned reinforcement, and drug-seeking behavior (Briand et al., 2010; Buffalari & See, 2011; Jennings et al., 2013; Mahler & Aston-Jones, 2012; Marcinkiewcz et al., 2016; Sartor & Aston-Jones, 2012).”
BackgroundLingg, R. T., Johnson, S. B., Emmons, E. B., Anderson, R. M., Romig‐Martin, S. A., Narayanan, N. S., McGaugh, J. L., LaLumiere, R. T., & Radley, J. J. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1915501117 · Cited by 26
“More recently, heterogeneity in BST functions have been parcellated relative to dorsal (69), posterior (70), and ventral (24, 71) regions, and these may be further distinguished by distinct neurochemically defined subpopulations within and spanning across these regions =473 20 Hz”
BackgroundBjorni, M., Rovero, N. G., Yang, E. R., Holmes, A., & Halladay, L. R. (2020) · Learning & Memory · doi:10.1101/lm.050807.119 · Cited by 25
“Some recent recording studies have identified opposing BNST populations that distinctly encode either anxiogenic or anxiolytic behaviors (Jennings et al. 2013, Kim et al. 2013).”
BackgroundIdentification of a personalized intracranial biomarker of depression and response to DBS therapy
Frank, A. C., Scangos, K. W., Larson, P., Norbu, T., Lee, A. T., & Lee, A. M. (2021) · Brain stimulation · doi:10.1016/j.brs.2021.06.009 · Cited by 21
“The correlation between BNST gamma activity and mood is consistent with studies demonstrating the BNSTs role in reward motivation pathways [9,10].”
Snyder, A. E., & Silberman, Y. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108814 · Cited by 22
Validation and extension of the reward-mountain model
Breton, Y.-A., Mullett, A., Conover, K. L., & Shizgal, P. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00125 · Cited by 22
Companion, M. A., & Thiele, T. E. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14222 · Cited by 22
“(2016) that a population of BNST glutamatergic neurons also coexpress a CRF+ phenotype, and research showing that a population of BNST glutamatergic neurons innervates the VTA and have effects on consummatory behavior (Jennings et al., 2013) together highlight the importance of future research to investigate the role…”
BackgroundHigh-Resolution Resting-State Functional Connectivity of the Extended Amygdala
Tomas, C. W., Huggins, A. A., Bennett, K. P., Parisi, E. A., & Larson, C. L. (2019) · Brain Connectivity · doi:10.1089/brain.2019.0688 · Cited by 21
“…have shown differential roles and connectivity within sub-components of the extended amygdala, and these differences have not been as well characterized in humans (Fox et al., 2015; Gungor and Pare, 2016; Jennings et al., 2013; Kalin et al., 2005; Oler et al., 2012; Stamatakis et al., 2014).”
Vicario, A., Abellán, A., & Medina, L. M. (2015) · Brain Behavior and Evolution · doi:10.1159/000381004 · Cited by 22
Sink, K. S., Davis, M., & Walker, D. L. (2013) · Learning & Memory · doi:10.1101/lm.032482.113 · Cited by 23
“In fact, results from the first such studies have now been reported (Jennings et al. 2013; Kim et al. 2013).”
BackgroundZhang, J., Xie, C., Xu, P., Tong, Q., Xiao, L., & Zhong, J. (2024) · Science Advances · doi:10.1126/sciadv.adp9413 · Cited by 21
“For example, the ventral BNST innervates the VTA, and stimulating GABAergic projections leads to anxiolytic phenotypes by inhibiting the VTA GABAergic neurons, while stimulating glutamatergic projections leads to anxiogenic phenotypes ( 73 ).”
Swart, J. M., Grattan, D. R., Ladyman, S. R., & Brown, R. S. E. (2021) · Hormones and Behavior · doi:10.1016/j.yhbeh.2021.105041 · Cited by 22
FKBP51 in the Oval Bed Nucleus of the Stria Terminalis Regulates Anxiety-Like Behavior
Engelhardt, C., Tang, F., Elkhateib, R., Bordes, J., Brix, L., van Doeselaar, L., Häusl, A., Pöhlmann, M., Schraut, K.-G., Yang, H.-Q., et al. (2021) · eNeuro · doi:10.1523/eneuro.0425-21.2021 · Cited by 20
“, 2013), and there is likely even a functional differentiation among cells located in the same BNST subnucleus (Jennings et al., 2013).”
BackgroundAllopregnanolone induces state-dependent fear via the bed nucleus of the stria terminalis
Acca, G. M., Mathew, A. S., Jin, J., Maren, S., & Nagaya, N. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.01.002 · Cited by 21
“Optogenetic and in vitro slice recording studies support the presence of heterogeneous subnuclei within the BNST that have opposing functions in regulating anxiety (Gungor et al., 2015; Jennings et al., 2013; Kim et al., 2013).”
Kaufling, J., Girard, D., Maître, M., Lesté-Lasserre, T., & Georges, F. E. (2017) · European Journal of Neuroscience · doi:10.1111/ejn.13554 · Cited by 21
“In accordance with anatomical data collected by Watanabe group (Kudo et al., 2012, 2014), Stuber and collaborators (Jennings et al., 2013) described a large predominance of GABAergic amBNST neurons projecting to non-DA (putatively GABAergic) neurons in the VTA, with a less predominant glutamatergic…”
BackgroundMethodResultInfluentialPedersen, W. S., Muftuler, L. T., & Larson, C. L. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.05.009 · Cited by 20
Güngör, N. Z., Yamamoto, R., & Paré, D. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0070-4 · Cited by 21
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New tools for understanding coping and resilience
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Lijffijt, M., Green, C. E., Balderston, N. L., Iqbal, T., Atkinson, M. E., Vo‐Le, B., Vo-Le, B., O’Brien, B., Grillon, C., Swann, A. C., et al. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00846 · Cited by 21
“Behavioral sensitization in general, and BNST reactivity specifically, may be under the control of NMDARs (66).”
BackgroundInfluentialNair, M. S., Dao, N. C., Melean, D. L., Griffith, K. R., Starnes, W. D., Moyer, J. B., Sicher, A. R., Brockway, D. F., Meeks, K. D., & Crowley, N. A. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.05.010 · Cited by 19
Cross-talk between the HPA axis and addiction-related regions in stressful situations
Nikbakhtzadeh, M., Ranjbar, H., Moradbeygi, K., Zahedi, E., Bayat, M., Soti, M., & Shabani, M. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e15525 · Cited by 24
“GABA afferents of BNST can inhibit the VTA GABAergic neurons and disinhibit the VTA DA neurons [20], while in an acute footshock stress situation, the BNST glutamatergic neurons showed an increment in firing rate, excited the VTA GABA neurons, and suppressed the dopaminergic firing rate [17].”
BackgroundGrogans, S. E., Hur, J., Barstead, M. G., Anderson, A. S., Islam, S., Kim, H. C., Kuhn, M., Tillman, R. M., Fox, A. S., Smith, J. F., et al. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1868-23.2024 · Cited by 22
Gomes‐de‐Souza, L., Bianchi, P., Ferreira, W. C., Tomeo, R. A., Cruz, F. C., & Crestani, C. C. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2021.110284 · Cited by 21
deBacker, J., Hawken, E. R., Normandeau, C. P., Jones, A. A., Prospero, C. D., Mechefske, E., Gregory, J. G., Hayton, S. J., & Dumont, É. C. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.182 · Cited by 20
“In fact, optogenetic activation of lateral hypothalamus-projecting dorsal BNST neurons provokes voracious feeding behaviors in mice (Jennings et al, 2013a).”
BackgroundThe neurobiology of parenting and infant-evoked aggression
Kaplan, H. S., Horvath, P. M., Rahman, M. M., & Dulac, C. G. (2024) · Physiological Reviews · doi:10.1152/physrev.00036.2023 · Cited by 20
Ressler, R. L., Goode, T. D., Evemy, C. G., & Maren, S. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107281 · Cited by 20
Loneliness-based impaired reward system pathway: Theoretical and clinical analysis and application
Wilkialis, L., Rodrigues, N. B., Majeed, A., Lee, Y. L., Lipsitz, O., Gill, H., Tamura, J. K., Nasri, F., Lui, L. M. W., Siegel, A. N., et al. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.113800 · Cited by 24
Reward prediction error in learning-related behaviors
Yujun, D., Song, D. F., Ni, J., Qing, H., & Quan, Z. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1171612 · Cited by 26
“…from the basolateral amygdala to the nucleus accumbens encode reward behaviors (Stuber et al., 2011), whereas glutamatergic projections from the basal ganglia to the ventral tegmental area encode aversive behaviors, and GABAergic projections encode positive behaviors (Jennings et al., 2013).”
BackgroundZhu, Y., Xie, S., Peng, A.-B., Yu, X., Li, C., Fu, J., Shen, C.-J., Cao, S.-X., Zhang, Y., Chen, J., et al. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.08.022 · Cited by 19
Mitten, E. H., Souders, A., de Velasco, E. M. F., & Wickman, K. (2024) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2024.1425607 · Cited by 20
“…VTA GABA neuron activity in mice can bi-directionally regulate real-time place preference and anxiety-related behavior (Tan et al., 2012; Jennings et al., 2013; Chen et al., 2020; Yu et al., 2021); activation of VTA GABA neurons is anxiogenic/aversive and inhibition is…”
BackgroundGeng, F., Zhang, J., Wu, J., Zou, W.-J., Liang, Z.-P., Bi, L., Liu, J., Kong, Y., Huang, C.-Q., Li, X., et al. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.05.018 · Cited by 19
“…with projecting counterparts that target glutamatergic neurons; however, the roles and underlying mechanisms of NRG1-ErbB4 signaling in different BNST subregions as well as in different subgroups of BNST GABAergic neurons, need to be further characterized (Jennings et al., 2013, Kim et al., 2013).”
BackgroundWarren, B. L., Suto, N., & Hope, B. T. (2017) · Frontiers in Neural Circuits · doi:10.3389/fncir.2017.00028 · Cited by 20
“Currently, the majority of studies attempting to investigate the neurobiology of memory assess ‘‘global’’ alterations and their functions within brain regions, neurons of a specific cell-type, or afferent/efferent connections between two brain areas, regardless of the specific neural activity patterns during behavior…”
BackgroundCho, K. K. A., & Sohal, V. S. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu225 · Cited by 19
“Another study used the approach described previously, to optogenetically tag glutamatergic or GABAergic neurons within the bed nucleus of the stria terminalis during recordings in vivo, and found that these neurons, which excite or inhibit non-dopaminergic VTA neurons, respectively, are activated or suppressed, respec…”
Background
Metadata
- Authors
- Jennings, J. H., Sparta, D. R., Stamatakis, A. M., Ung, R. L., Pleil, K. E., Kash, T. L., & Stuber, G. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Stuber, Garret D.
- ORCID
- Venue
- Nature
- Published
- 2013-03-20
- Volume
- 496
- Issue
- 7444
- Pages
- 224-228
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3778934
- OpenAlex
- W2067203693
- Semantic Scholar
- b094f8c7bc24b675130d787985a6c38dc2555363
- Cited by
- 704
- References
- 33
- Citations by year
- 2026: 34 · 2025: 53 · 2024: 30 · 2023: 44 · 2022: 35 · 2021: 65 · 2020: 43 · 2019: 55 · 2018: 57 · 2017: 55 · 2016: 78 · 2015: 66 · 2014: 58 · 2013: 29
- FWCI
- 37.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Foundation for the National Institutes of Health
- Whitehall Foundation
- National Institute on Alcohol Abuse and Alcoholism (F32AA018610, AA011605, AA 007573, F32AA021043, AA018610, AA021043, P60AA011605, T32AA007573)
- National Institute on Drug Abuse (F31DA034472, R01DA032750, DA034472, DA029325, R21DA029325, DA032750, R37DA032750)
- National Institute of Neurological Disorders and Stroke (P30NS045892, NS 007431, T32NS007431)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- bed nucleus of the stria terminalis, ventral tegmental area, extended amygdala, glutamatergic projections, GABAergic projections, anxiety, reward, aversion, motivational states, depression, channelrhodopsin-2, aversive stimuli
- MeSH terms
- Channelrhodopsins, Amygdala, Animals, Anxiety, Avoidance Learning, Behavior, Animal, Cues, Electroshock, Glutamine, Male, Mice, Inbred C57BL, Motivation, Phenotype, Reward, Septal Nuclei, Ventral Tegmental Area, Mice, GABAergic Neurons, Optogenetics
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