The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index; none of the 1 sources its claims cite is checked for support yet.
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.
Overview
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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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21 Own method · 15 Own result · 8 Own interpretation · 1 Not checked yet
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
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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 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
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
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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
plain- Asserted: passes — The authors put it forward as true.
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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
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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
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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
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“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
hedged- Asserted: passes — The authors put it forward as true.
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“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
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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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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
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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
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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
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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
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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
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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
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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
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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
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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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“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
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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
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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
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Claims other papers make about this one
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The cited source says what the claim attributes to it.
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
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
“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]
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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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > Experimental subjects and stereotactic surgery
“For all in vivo electrophysiology experiments, mice were implanted with a 16-wire (4 × 4 configuration, wire diameter∼30µm) tungsten multielectrode array (MEA)”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo anesthetized electrophysiology
“Extracellular neural activity was recorded using a glass recording electrode (5 − 10 MΩ: and filled with 0.5 M NaCl).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > Experimental subjects and stereotactic surgery
“For all in vivo electrophysiology experiments, male mice were unilaterally injected with 0.5 µl of purified and concentrated adeno-associated virus (AAV)”
§ Distinct extended amygdala circuits for divergent motivational states > Online methods > In vivo anesthetized electrophysiology
“C57BL/6J mice were bilaterally injected with 0.3 µl of AAV5-CaMKIIa-ChR2-eYFP into the BNSTv.”
Citations
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Millisecond-timescale, genetically targeted optical control of neural activity
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., & Deisseroth, K. A. (2005) · Nature Neuroscience · doi:10.1038/nn1525 · Cited by 5,015
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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…”
BackgroundMethodThe mesolimbic dopamine reward circuit in depression
Nestler, E. J., & Carlezon, W. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.018 · Cited by 2,059 · cited 3×
“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…”
BackgroundMethodPhasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety
Davis, M., Walker, D. L., Miles, L., & Grillon, C. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.109 · Cited by 1,513
Neuron-type-specific signals for reward and punishment in the ventral tegmental area
Cohen, J. Y., Haesler, S., Vong, L., Lowell, B. B., & Uchida, N. (2012) · Nature · doi:10.1038/nature10754 · Cited by 1,318
Input-specific control of reward and aversion in the ventral tegmental area
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Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons
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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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Cited by
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Items 201–300 of 703
Patrono, E., Gasbarri, A., Tomaz, C. A. B., & Nishijo, H. (2016) · Medical Hypotheses · doi:10.1016/j.mehy.2016.05.015 · Cited by 60
“emotional, and habitual effects of drug addiction [63-66].”
BackgroundDefensive Behaviors Driven by a Hypothalamic-Ventral Midbrain Circuit
Mangieri, L. R., Jiang, Z., Lu, Y., Xu, Y., Cassidy, R. M., Justice, N. J., Xu, Y., Arenkiel, B. R., & Tong, Q. (2019) · eNeuro · doi:10.1523/eneuro.0156-19.2019 · Cited by 58
“…the hypothalamus has been previously regarded as a relay station for unconditioned defensive behaviors (Canteras, 2008), our study and others (Jennings et al., 2013a; Sternson, 2013; Kunwar et al., 2015) support the idea that discrete hypothalamic nuclei are sufficient for generating…”
BackgroundMethodGüngör, N. Z., Yamamoto, R., & Paré, D. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00677.2015 · Cited by 64
Pati, D., Marcinkiewcz, C. A., DiBerto, J. F., Cogan, E. S., McElligott, Z. A., & Kash, T. L. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107759 · Cited by 59
“While activation of BNST-GABAergic terminals in the LH produced robust feeding behavior (Jennings et al, 2013a), stimulation of anterodorsal BNST inputs to the LH resulted in anxiolysis without affecting reward-related behaviors (Kim et al, 2013).”
BackgroundInfluentialSelf-citationRadley, J. J., & Sawchenko, P. E. (2015) · The Journal of Comparative Neurology · doi:10.1002/cne.23815 · Cited by 58
“Whereas earlier behavioral studies tended to treat the BST as a homogeneous entity, recent work has defined cytoarchitectonic subdivisions of the BST that are associated with distinct types of adaptive behavioral and autonomic responses (Jennings et al., 2013; Kim et al., 2013).”
ResultVentral pallidal regulation of motivated behaviors and reinforcement
Soares‐Cunha, C., & Heinsbroek, J. A. (2023) · Frontiers in Neural Circuits · doi:10.3389/fncir.2023.1086053 · Cited by 63
Specificity and impact of adrenergic projections to the midbrain dopamine system
Mejías-Aponte, C. A. (2016) · Brain Research · doi:10.1016/j.brainres.2016.01.036 · Cited by 58
“Recently two pathways with preferential inputs to non-DA neurons have been described; a GABAergic input by nucleus accumbens (NAcc) medium spiny neurons (Xia et al., 2011), and GABAergic and glutamatergic inputs from the bed nucleus of the stria terminalis (Jennings et al., 2013).”
BackgroundNew Opportunities in Vasopressin and Oxytocin Research: A Perspective from the Amygdala
Stoop, R., Hegoburu, C., & van den Burg, E. H. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-033904 · Cited by 61
“The amygdala has been implicated in both aversive and appetitive learning (Barberini et al. 2012), and it is possible that the OTRs and VPRs govern these associative learning behaviors in a complementary manner throughout these regions ( Jennings et al. 2013).”
BackgroundTao, C., Zhang, G., Huang, J., Li, Z., Tao, H. W., & Zhang, L. I. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01397-2 · Cited by 62
Recent advances in understanding the role of the hypothalamic circuit during aggression
Falkner, A. L., & Lin, D. (2014) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2014.00168 · Cited by 60
“In future studies, this hypothesis and others could be tested by combining projection specific tagging and electrophysiology to compare electrophysiological responses with connectivity (Jennings et al., 2013).”
BackgroundNeurobiological mechanisms that contribute to stress-related cocaine use
Mantsch, J. R., Vranjkovic, O., Twining, R. C., Gasser, P. J., McReynolds, J. R., & Blacktop, J. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.07.021 · Cited by 63
Reward from bugs to bipeds: a comparative approach to understanding how reward circuits function
Scaplen, K. M., & Kaun, K. R. (2016) · Journal of Neurogenetics · doi:10.1080/01677063.2016.1180385 · Cited by 60
“Conversely, inhibiting VTA GABA neurons disinhibits VTA dopamine neurons, inducing an appetitive response (Jennings et al., 2013).”
BackgroundTools for Resolving Functional Activity and Connectivity within Intact Neural Circuits
Jennings, J. H., & Stuber, G. D. (2014) · Current Biology · doi:10.1016/j.cub.2013.11.042 · Cited by 54
“Therefore, phototagging of genetically defined neurons in a projection-specific fashion can further define and refine the computational role of participant cells within a complex circuit [2].”
InfluentialSelf-citationMcHenry, J. A., Rubinow, D. R., & Stuber, G. D. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.04.001 · Cited by 57
Self-citationPBN-PVT projections modulate negative affective states in mice
Zhu, Y.-B., Wang, Y., Hua, X.-X., Xu, L., Liu, M.-Z., Zhang, R., Liu, P.-F., Li, J.-B., Zhang, L., & Mu, D. (2022) · eLife · doi:10.7554/elife.68372 · Cited by 57
“The BNST and CeA have been 478 previously implicated in negative affective behaviors (Jennings et al., 2013; 479 Tye et al., 2011).”
BackgroundGlangetas, C., Massi, L., Fois, G. R., Jalabert, M., Girard, D., Diana, M., Yonehara, K., Roska, B., Xu, C., Lüthi, A., et al. (2017) · Nature Communications · doi:10.1038/ncomms14456 · Cited by 57
“Here, we demonstrate: (1) that both vSUB/CA1 and ILCx converge on the same amBNST neurons; (2) that in vivo stimulation of the vSUB/CA1 promotes an N-methyl-D-aspartic acid or N-methyl-Daspartate (NMDA)-dependent long term potentiation (LTP) at the vSUB/CA1-amBNST synapses (LTPvSUB/CA1), associated with an NMDA-indepe…”
Reward-Predictive Neural Activities in Striatal Striosome Compartments
Yoshizawa, T., Ito, M., & Doya, K. (2018) · eNeuro · doi:10.1523/eneuro.0367-17.2018 · Cited by 53
“A recent study revealed anatomic connections to striosomes from the bed nucleus of the stria terminalis (Smith et al., 2016), which is known to be involved in fear or anxiety (Jennings et al., 2013; Kim et al., 2013).”
BackgroundKim, B.-K., Yoon, S., Nakajima, R., Lee, H. J., Lim, H. J., Lee, Y.-K., Choi, J.-S., Yoon, B.-J., Augustine, G. J., & Baik, J. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811664115 · Cited by 56
“A recent study revealed that photostimulation of distinct BNST subregions exerts opposite effects in modulating anxiety, due to the different projections produced by the different neuronal populations of these different subregions (54, 55).”
BackgroundRole of the Bed Nucleus of the Stria Terminalis in PTSD: Insights From Preclinical Models
Miles, O. W., & Maren, S. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00068 · Cited by 59
Xiao, C., Wei, J., Zhang, G., Tao, C., Huang, J., Shen, L., Wickersham, I. R., Tao, H. W., & Zhang, L. I. (2023) · Neuron · doi:10.1016/j.neuron.2023.02.012 · Cited by 58
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“In this regulatory system, VTA GABAergic neurons play a central role (Tan et al., 2012; van Zessen et al., 2012; Jennings et al., 2013) and are modulated by opioids (Johnson & North, 1992a).”
BackgroundInfluentialSynaptic function and plasticity in identified inhibitory inputs onto VTA dopamine neurons
Polter, A. M., Barcomb, K., Tsuda, A. C., & Kauer, J. A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13879 · Cited by 54
“nucleus of the stria terminalis (BNST; Jennings et al., 2013) and the nucleus accumbens (Xia et al.”
BackgroundCircuit-Based Biomarkers for Mood and Anxiety Disorders
Xia, F., & Kheirbek, M. A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.08.004 · Cited by 56
“Inhibition of vHPC–LHA projections in mice increases open arm exploration in the EPM, while modulation of vHPC–amygdala projections has no effect on anxiety, but modulates learned fear [29].”
BackgroundInfluentialSensory input, sex and function shape hypothalamic cell type development
Kaplan, H. S., Logeman, B. L., Zhang, K., Yawitz, T. A., Santiago, C., Sohail, N., Talay, M., Seo, C., Naumenko, S., Sui, S. J. H., et al. (2025) · Nature · doi:10.1038/s41586-025-08603-0 · Cited by 51
Synaptic Plasticity onto Dopamine Neurons Shapes Fear Learning
Pignatelli, M., Umanah, G. K. E., Ribeiro, S. P., Chen, R., Karuppagounder, S. S., Yau, H., Eacker, S. M., Dawson, V. L., Dawson, T. M., & Bonci, A. (2017) · Neuron · doi:10.1016/j.neuron.2016.12.030 · Cited by 59
Dynamic Neural Interactions Supporting the Cognitive Reappraisal of Emotion
Steward, T., Davey, C. G., Jamieson, A. J., Stephanou, K., Soriano-Mas, C., Felmingham, K. L., & Harrison, B. J. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhaa268 · Cited by 52
Alcohol and basal ganglia circuitry: Animal models
Lovinger, D. M., & Alvarez, V. A. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.03.023 · Cited by 52
Radley, J. J., & Johnson, S. B. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.12.005 · Cited by 57
“…been previously contrasted from its dorsal counterpart. avBST involvement in anxietylike behaviors has been demonstrated (Glangetas et al., 2017; Jennings et al., 2013; Marcinkiewcz et al., 2016), but both the intrinsic connectivity between dorsal and ventral BST, and comorbidity of anxiety and…”
BackgroundNeurobiology of alcohol seeking behavior
Domi, E., Domi, A., Adermark, L., Heilig, M. A., & Augier, E. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15343 · Cited by 53
“In contrast, activity of a smaller population of glutamatergic BNST inputs to the VTA is anxiogenic and aversive (Jennings et al., 2013; Kudo et al., 2012).”
BackgroundGlangetas, C., Girard, D., Groc, L., Marsicano, G., Chaouloff, F., & Georges, F. E. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3175-13.2013 · Cited by 52
“The BNST has been associated with stress and negative emotional state (Ulrich-Lai and Herman, 2009), and recent optogenetic findings have revealed how that structure controls aversive and motivational behaviors (Jennings et al., 2013; Kim et al., 2013).”
BackgroundLkhagvasuren, B., Oka, T., Nakamura, Y., Hayashi, H., Sudo, N., & Nakamura, K. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.047 · Cited by 50
“…from the ventral divisions of the BNST to the ventral tegmental area are involved in different emotion-related behaviors: stimulation of the former pathway results in aversive and anxiogenic behavioral phenotypes and the latter produces rewarding and anxiolytic phenotypes (Jennings et al., 2013).”
Ventral tegmental area subcircuits process rewarding and aversive experiences
Bariselli, S., Glangetas, C., Tzanoulinou, S., & Bellone, C. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13779 · Cited by 52
Laurent, R. S., Damonte, V. M., Tsuda, A. C., & Kauer, J. A. (2020) · Neuron · doi:10.1016/j.neuron.2020.02.029 · Cited by 51
“Activating RMTgGABA/VTA Synapses Is Aversive Silencing local GABAergic interneurons in the VTA induces appetitive behaviors (Jennings et al., 2013), while the activation of these interneurons is aversive and disrupts reward consumption (Tan et al.”
BackgroundMotzkin, J. C., Philippi, C. L., Oler, J. A., Kalin, N. H., Başkaya, M. K., & Koenigs, M. R. (2014) · Cortex · doi:10.1016/j.cortex.2014.11.013 · Cited by 50
“A study in rodents using optogenetics to activate and deactivate discrete subpopulations of BNST neurons found that focal stimulation of adjacent BNST subregions elicited opposing anxiolytic and anxiogenic effects (Jennings et al., 2013; Kim et al., 2013).”
BackgroundHippocampal Hyperactivity as a Druggable Circuit-Level Origin of Aberrant Salience in Schizophrenia
Kätzel, D., Wolff, A. R., Bygrave, A. M., & Bannerman, D. M. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.486811 · Cited by 51
CRHCeA→VTA inputs inhibit the positive ensembles to induce negative effect of opiate withdrawal
Jiang, C., Yang, X., He, G., Wang, Z., Wang, Z., Xu, W., Ma, L., Ma, L., & Wang, F. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01321-9 · Cited by 49
Prospective Coding of Dorsal Raphe Reward Signals by the Orbitofrontal Cortex
Zhou, J., Jia, C., Feng, Q., Bao, J., & Luo, M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4017-14.2015 · Cited by 49
“…tagging method has been used to facilitate the classification of recorded cells in several brain areas (Gradinaru et al., 2007; Lima et al., 2009; Cardin et al., 2010; Anikeeva et al., 2012; Cohen et al., 2012; Jennings et al., 2013; Kim et al., 2013; Kvitsiani et al., 2013; Liu et al., 2014).”
MethodThoresen, J. C., Francelet, R., Çöltekin, A., Richter, K., Fabrikant, S. I., & Sandi, C. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.04.008 · Cited by 49
The antidepressant effect of light therapy from retinal projections.
Li, X., & Li, X. (2018) · Neuroscience Bulletin · doi:10.1007/s12264-018-0210-1 · Cited by 47
“ulate stress-anxiety and depression [76, 85], respectively.”
BackgroundCentral regulation of body fluid homeostasis
Noda, M., & Matsuda, T. (2022) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.98.016 · Cited by 48
Butler, R. K., Oliver, E. M., Sharko, A. C., Parrilla-Carrero, J., Kaigler, K. F., Fadel, J. R., & Wilson, M. A. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.01.051 · Cited by 46
Onaolapo, O. J., Aremu, O. S., & Onaolapo, A. Y. (2017) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-017-1371-6 · Cited by 47
Generality and opponency of rostromedial tegmental (RMTg) roles in valence processing
Li, H., Pullmann, D., Cho, J. Y., Eid, M., & Jhou, T. C. (2019) · eLife · doi:10.7554/elife.41542 · Cited by 50
“However, the sources of the GABAergic transmissions are still unknown, and have been proposed to arise from numerous possible sources including not only the RMTg, but also the lateral hypothalamus, ventral pallidum, extended amygdala, and GABAergic neurons in the VTA (Jennings et al., 2013; Tian et al., 2016).”
BackgroundVentral Pallidum GABA Neurons Mediate Motivation Underlying Risky Choice
Farrell, M. R., Esteban, J. S. D., Faget, L. C., Floresco, S., Hnasko, T. S., & Mahler, S. V. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2039-20.2021 · Cited by 45
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“This work and associated studies in which specific inputs to ventral tegmental dopamine neurons were manipulated optogenetically (Britt et al. 2012; Jennings et al. 2013) demonstrate the promise of the new methods to overcome technical obstacles to determining the neural underpinnings of reward…”
Demaestri, C., Brenhouse, H. C., & Honeycutt, J. A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.12.005 · Cited by 42
“Adding nuance to this narrative, activation of different subtypes of neurons within the BNST lead to dissociable responses, such that activation of GABAergic neurons within the BNST impart anxiolysis, whereas activation of glutamatergic projections from the BNST is anxiogenic [72].”
McReynolds, J. R., Vranjkovic, O., Thao, M., Baker, D. L., Makky, K., Lim, Y. W., & Mantsch, J. R. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3535-0 · Cited by 45
“The BNST sends both glutamatergic and GABAergic projections to the VTA (Georges and Aston-Jones 2001; Kudo et al. 2012), which appear to have distinct roles in reward and aversion (Jennings et al. 2013).”
Siuda, E. R., Al‐Hasani, R., McCall, J. G., Bhatti, D. L., & Bruchas, M. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.371 · Cited by 50
“For example, in vivo photostimulation of BNST glutamatergic projections is both aversive and anxiogenic (Jennings et al., 2013), while activation of BLA terminals specifically in the CeA is anxiolytic (Tye et al.”
BackgroundDrug withdrawal conceptualized as a stressor
Chartoff, E. H., & Carlezon, W. A. (2014) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000080 · Cited by 44
“Footshock enhances BNST–VTA neuronal activity, and selective optogenetic stimulation of BNST–VTA glutamatergic fibers produces aversion and anxiety-like behavior (Jennings et al., 2013).”
BackgroundLuster, B. R., Cogan, E. S., Schmidt, K. T., Pati, D., Pina, M. M., Dange, K., & McElligott, Z. A. (2019) · Addiction Biology · doi:10.1111/adb.12748 · Cited by 45
“Furthermore, the BNST is known to regulate feeding, fear, anxiety‐, and reward‐like behaviors via projections to the VTA and LH.(31,32,46) In male rodents, spontaneous and naloxone‐precipitated withdrawal inhibits activity of VTA dopamine neurons(13,20) and hence reduces dopamine release in the nucleus accumbens.”
BackgroundGiardino, W. J., & Pomrenze, M. B. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.613025 · Cited by 48
Chocyk, A., Majcher‐Maślanka, I., Przyborowska, A., Maćkowiak, M., & Wędzony, K. (2015) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2015.05.002 · Cited by 45
“…phenomenon is that a greater number of nondopaminergic neurons results in a proportionally greater number of inhibitory inputs received by the VTA from other brain regions, e.g., from the nucleus accumbens or bed nucleus of the stria terminalis (BNST) (Jennings et al., 2013; Creed et al., 2014).”
BackgroundInfluentialThe therapeutic potential of exercise for neuropsychiatric diseases: A review
Swenson, S., Blum, K., McLaughlin, T., Gold, M. S., & Thanos, P. K. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116763 · Cited by 42
Neurochemical Signaling of Reward and Aversion to Ventral Tegmental Area Glutamate Neurons
McGovern, D. J., Polter, A. M., & Root, D. H. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.1419-20.2021 · Cited by 42
Horrell, N. D., Hickmott, P. W., & Wendy Saltzman, A. (2018) · Current topics in behavioral neurosciences · doi:10.1007/7854_2018_55 · Cited by 45
Chen, L., Lu, Y., Chen, H., Huang, S., Guo, Y.-R., Zhang, J.-Y., Li, Q.-X., Luo, C., Lin, S., Chen, Z.-N., et al. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108114 · Cited by 41
Wang, J., Sun, L., Chen, L., Sun, J., Xie, Y., Tian, D., Gao, L., Zhang, D., Xia, M., & Wu, T. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00469-1 · Cited by 42
The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in mice
Pina, M. M., Young, E. A., Ryabinin, A. E., & Cunningham, C. L. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.08.033 · Cited by 42
Vento, P. J., Burnham, N. W., Rowley, C. S., & Jhou, T. C. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.10.018 · Cited by 46
Awasthi, S., Pan, H., LeDoux, J. E., Cloître, M., Altemus, M. M., McEwen, B. S., Silbersweig, D., & Stern, E. R. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102442 · Cited by 42
A Scientometric Approach to Review the Role of the Medial Preoptic Area (MPOA) in Parental Behavior
Carollo, A., Balagtas, J. P. M., Neoh, M. J. Y., & Esposito, G. (2021) · Brain Sciences · doi:10.3390/brainsci11030393 · Cited by 41
Cell-type diversity in the bed nucleus of the stria terminalis to regulate motivated behaviors
Ortiz-Juza, M. M., Alghorazi, R., & Rodríguez-Romaguera, J. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113401 · Cited by 43
Mutation of Elfn1 in Mice Causes Seizures and Hyperactivity
Dolan, J., & Mitchell, K. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080491 · Cited by 45
“Though habenular function has been implicated in regulating anxiety levels [79,84,88,89], this kind of phenotype could also be related to Elfn1 functions in any number of other regions, most obviously including the septum, extended amygdala and hippocampus [90,91].”
BackgroundGüngör, N. Z., & Paré, D. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3473-13.2014 · Cited by 41
“, 2013) or of different cell types within these regions (Jennings et al., 2013) revealed that BNST is functionally heterogeneous.”
BackgroundBruzsik, B., Bíró, L., Zelena, D., Sipos, E., Szebik, H., Sarosdi, K. R., Horváth, O., Farkas, I., Csillag, V., Finszter, C. K., et al. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.1944-20.2020 · Cited by 40
Anxious to see you: Neuroendocrine mechanisms of social vigilance and anxiety during adolescence
Wright, E. C., Hostinar, C. E., & Trainor, B. C. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14628 · Cited by 55
“Interestingly, ventral hippocampus also has strong connections with ventral BNST (Cullinan, Herman, & Watson, 1993), which also can drive anxiogenic states (Jennings et al., 2013).”
BackgroundGlangetas, C., Fois, G. R., Jalabert, M., Lecca, S., Valentinova, K., Meye, F. J., Diana, M., Fauré, P., Mameli, M., Caillé, S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.076 · Cited by 40
“…to clarify the distinct sub-circuit supporting inhibitory responses, but because both GABAergic and glutamatergic projections from the BNST to the VTA have been identified (Georges and Aston-Jones, 2001; Jennings et al., 2013; Kudo et al., 2012), the BNST-VTA pathway could be a potential candidate.”
InfluentialDissecting Brain Networks Underlying Alcohol Binge Drinking Using a Systems Genomics Approach
Ferguson, L. B., Zhang, L., Kircher, D. M., Wang, S., Mayfield, R. D., Crabbe, J. C., Morrisett, R. A., Harris, R. A., & Ponomarev, I. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1252-0 · Cited by 40
A neural mechanism for learning from delayed postingestive feedback
Zimmerman, C. A., Bolkan, S. S., Pan-Vazquez, A., Wu, B., Keppler, E., Meares-Garcia, J. B., Guthman, E. M., Fetcho, R. N., McMannon, B., Lee, J., et al. (2025) · Nature · doi:10.1038/s41586-025-08828-z · Cited by 49
Accanto, N., Chen, I.-W., Ronzitti, E., Molinier, C., Tourain, C., Papagiakoumou, E. I., & Emiliani, V. (2019) · Scientific Reports · doi:10.1038/s41598-019-43933-w · Cited by 41
Contemporary approaches to neural circuit manipulation and mapping: focus on reward and addiction
Saunders, B. T., Richard, J. M., & Janak, P. H. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0210 · Cited by 40
Inhibitory Plasticity of Mesocorticolimbic Circuits in Addiction and Mental Illness
Ostroumov, A., & Dani, J. A. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.07.014 · Cited by 43
Noradrenergic circuits and signaling in substance use disorders
Downs, A. M., & McElligott, Z. A. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.108997 · Cited by 37
Applications of optogenetic and chemogenetic methods to seizure circuits: Where to go next?
Forcelli, P. A. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24135 · Cited by 37
“When optogenetic stimulation is applied to terminal fields (Jennings et al., 2013; Sato, Häusser, & Carandini, 2014), an antidromically propagating action potential can be triggered; in turn, this may result in an orthodromic spike.”
Threat imminence dictates the role of the bed nucleus of the stria terminalis in contextual fear
Goode, T. D., Acca, G. M., & Maren, S. (2019) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2019.107116 · Cited by 36
Kim, I. H., Kim, N., Kim, S., Toda, K., Catavero, C. M., Courtland, J. L., Yin, H. H., & Soderling, S. H. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107965 · Cited by 36
“Behavior The real-time social preference procedure was designed based on a real-time conditioned place preference task(Jennings et al., 2013; Stamatakis and Stuber, 2012).”
MethodMasugi-Tokita, M., Flor, P. J., & Kawata, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.198 · Cited by 35
“The BNSTa is currently receiving increased attention, because this area regulates several emotional and motivational processing and because some components of the important pathways in the BNSTa have been revealed, despite the complex circuits involved (Kim et al, 2013; Jennings et al, 2013a, b).”
BackgroundScheyer, A. F., Yasmin, F., Naskar, S., & Patel, S. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01438-7 · Cited by 37
“Repeated administration of these substances induces adaptive changes in DA reward circuitry leading to attenuated release in both rodent and human models [227, 228], and simultaneously induces adaptive changes in the amygdala, leading to enhanced stress-reactivity and negative affect which promote negative reinforceme…”
BackgroundA neuronal coping mechanism linking stress-induced anxiety to motivation for reward
Klenowski, P. M., Zhao-Shea, R., Freels, T. G., Molas, S., Zinter, M., M'angale, P. G., Xiao, C., Martínez‐Núñez, L., Thomson, T., & Tapper, A. R. (2023) · Science Advances · doi:10.1126/sciadv.adh9620 · Cited by 38
“Stress induces anxiety-like behavior via brain areas that respond to aversive and stressful stimuli, including the prefrontal cortex ( 5 – 8 ), amygdala ( 9 – 11 ), bed nucleus of the stria terminalis ( 12 – 14 ), and ventral hippocampus ( 15 – 17 ).”
BackgroundPelrine, E. R., Pasik, S. D., Bayat, L., Goldschmiedt, D., & Bauer, E. P. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.10.008 · Cited by 36
Nordman, J. C., Ma, X., & Li, Z. (2020) · eNeuro · doi:10.1523/eneuro.0147-20.2020 · Cited by 38
“…by social and physical stress, with the VmH driving defensive responses to a predator and the VmH and BNST regulating anxiolytic responses to foot shock (Dennis, 1976; Jennings et al., 2013; Kim et al., 2013; Silva et al., 2013; Anthony et al., 2014; Butler et al., 2015; Zelikowsky et al., 2018).”
BackgroundCan transsynaptic viral strategies be used to reveal functional aspects of neural circuitry?
Rogers, A. D., & Beier, K. T. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.109005 · Cited by 37
Vicario, A., Mendoza, E., Abellán, A., Scharff, C., & Medina, L. M. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1229-6 · Cited by 36
“For example, are the GABA BSTL-VTA projecting cells (Kudo et al. 2012; Jennings et al. 2013a; as noted above, these are involved in reward and anxiolysis) the same as those projecting to the lateral hypothalamus, which are involved in motivational regulation of feeding (Jennings et al. 2013b)?”
Background5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects
Cerasa, A., Quattrone, A., Piras, F., Mangone, G., Magariello, A., Fagioli, S., Girardi, P., Muglia, M., Caltagirone, C., & Spalletta, G. (2014) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nst144 · Cited by 35
“It has been proposed that these behaviours are fundamentally regulated by activity of the amygdala (Jennings et al., 2013), especially in the right side (Li et al.”
BackgroundMcReynolds, J. R., Peña, D. F., Blacktop, J. M., & Mantsch, J. R. (2013) · Stress · doi:10.3109/10253890.2013.872617 · Cited by 33
“…the BNST to the VTA have been characterized (Georges & Aston-Jones, 2001; Kudo et al., 2012), and a recent optogenetic study identified distinct roles for the GABAergic and glutamatergic projections to the VTA resulting in rewarding and aversive phenotypes, respectively (Jennings et al., 2013).”
BackgroundInfluentialNicotine Self-Administration Induces CB1-Dependent LTP in the Bed Nucleus of the Stria Terminalis
Reisiger, A.-R., Kaufling, J., Manzoni, O. J., Cador, M., Georges, F. E., & Caillé, S. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3149-13.2014 · Cited by 37
“Much evidence implicates the BNST in stress and anxiety (Glangetas et al., 2013; Jennings et al., 2013).”
BackgroundYamauchi, N., Takahashi, D., Sugimura, Y. K., Kato, F., Amano, T., & Minami, M. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14165 · Cited by 37
“As Jennings et al. (2013) used 20 Hz photostimulation to examine the effect of optogenetic activation of the BNST- VTA pathway on anxiety- like behaviors in an elevated plus- maze test, we used 20 Hz photostimulation in this study.”
BackgroundMethodResultInfluentialLong-Range GABAergic Projections of Cortical Origin in Brain Function
Urrutia-Piñones, J., Morales-Moraga, C., Sanguinetti, N. K., Escobar, A. P., & Chiu, C. Q. (2022) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2022.841869 · Cited by 36
Pati, D., Pina, M. M., & Kash, T. L. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0349-0 · Cited by 35
“BNST-VTA projections are thought to preferentially innervate non-dopaminergic VTA neurons (Jennings et al, 2013), and can indirectly increase the activity of dopamine neurons by disinhibiting GABAergic neurons in the VTA.”
BackgroundInfluentialSelf-citationSexual differentiation of neural mechanisms of stress sensitivity during puberty
Wright, E. C., Luo, P. X., Zakharenkov, H. C., Serna Godoy, A., Lake, A. A., Prince, Z. D., Sekar, S., Culkin, H. I., Ramirez, A. V., Dwyer, T., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2306475120 · Cited by 34
An open-source platform for head-fixed operant and consummatory behavior
Gordon-Fennell, A., Barbakh, J. M., Utley, M. T., Singh, S., Bazzino, P., Gowrishankar, R., Bruchas, M. R., Roitman, M. F., & Stuber, G. D. (2023) · eLife · doi:10.7554/elife.86183 · Cited by 32
“…we determined if OHRBETS can measure operant responding to obtain or avoid optogenetic stimulation of brain circuits that have been previously established to be rewarding or aversive in freely moving rodents ( Chen et al., 2020 ; Jennings et al., 2015 ; Jennings et al., 2013 ; Rossi et al., 2019 ).”
Self-citationNagano, Y., Kaneda, K., Maruyama, C., Ide, S., Kato, F., & Minami, M. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.05.059 · Cited by 34
Pina, M. M., & Cunningham, C. L. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.11.013 · Cited by 34
“, 2014), vBNST-VTA GABA in reward, and vBNST-VTA glutamate in aversion and anxiety (Jennings et al., 2013).”
BackgroundOptogenetics and its application in pain and anxiety research
Jarrin, S., & Finn, D. P. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.08.007 · Cited by 34
Zhou, C., Wu, Y., Ding, X., Shi, N., Cai, Y., & Pan, Z. Z. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1259-19.2020 · Cited by 35
“…of the AAV vectors under the control of the CaMKII promoter for manipulating SIRT1 expression in this study, optical activation of neurons in the bed nucleus of the stria terminalis through CaMKII promoter-controlled channelrhodopsin produces GABAergic synaptic currents (Jennings et al., 2013).”
BackgroundMethodSong, Y., Meng, Q., Wu, K., Hua, R., Song, Z., Song, Y., Qin, X., Cao, J., & Zhang, Y. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104690 · Cited by 34
A midbrain dynorphin circuit promotes threat generalization
Fellinger, L., Jo, Y. S., Hunker, A. C., Soden, M. E., Elum, J. E., Juarez, B., & Zweifel, L. S. (2021) · Current Biology · doi:10.1016/j.cub.2021.07.047 · Cited by 34
Illuminating subcortical GABAergic and glutamatergic circuits for reward and aversion
Gordon-Fennell, A., & Stuber, G. D. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108725 · Cited by 38
Self-citationOptogenetics, physiology, and emotions
Kravitz, A. V., & Bonci, A. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00169 · Cited by 35
“This impressive trifecta has been accomplished by a few studies to date [e.g., (Jennings et al., 2013; Tye et al., 2013)].”
BackgroundMarcinkiewcz, C. A., Rosa, G. B.-D. L., Dorrier, C., McKnight, M., DiBerto, J. F., Pati, D., Gianessi, C. A., Hon, O. J., Tipton, G., McElligott, Z. A., et al. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00594 · Cited by 33
Self-citation
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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