The hippocampal-VTA loop: controlling the entry of information into long-term memory
Open accessAbstract
In this article we develop the concept that the hippocampus and the midbrain dopaminergic neurons of the ventral tegmental area (VTA) form a functional loop. Activation of the loop begins when the hippocampus detects newly arrived information that is not already stored in its long-term memory. The resulting novelty signal is conveyed through the subiculum, accumbens, and ventral pallidum to the VTA where it contributes (along with salience and goal information) to the novelty-dependent firing of these cells. In the upward arm of the loop, dopamine (DA) is released within the hippocampus; this produces an enhancement of LTP and learning. These findings support a model whereby the hippocampal-VTA loop regulates the entry of information into long-term memory.
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The hippocampus and substantia nigra are key to detecting novelty and evaluating its reward value.
“The hippocampus and substantia nigra (a basal ganglia structure) are central to novelty detection and reward evaluation of novelty (Bunzeck and Düzel, 2006; Lisman and Grace, 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Lisman and Grace, 2005
Hippocampal functional connections activate VTA neurons.
“Although functional connections from the hippocampus activate VTA neurons (57)”
From Neuroanatomic differences associated with stress susceptibility and resilience (2016) · cites this paper as [57]
DA and ACh neurotransmission play critical roles in the regulation of memory via the ventral tegmental area and MSDB projections to the PFC-hippocampus-associated circuits.
“DA and ACh neurotransmission play critical roles in the regulation of memory via the ventral tegmental area and MSDB projections to the PFC-hippocampus-associated circuits”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Lisman and Grace, 2005
Our results provide novel insights into the relationship between midbrain dopaminergic neurons, encoding salient information about an environment, and hippocampal assemblies, providing representations of space, in modulating memory according to the value of the information to be remembered.
“Our results thus provide novel insights into the relationship between midbrain dopaminergic neurons, encoding salient information about an environment9,10,16,19,20, and hippocampal assemblies, providing representations of space1-3, in modulating memory according to the value of the information to be remembered.”
From Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence (2014) · cites this paper as [10]
The contribution of dopamine towards hippocampal neuronal dynamics associated with memory persistence remains to be identified.
“However the contribution of dopamine towards hippocampal neuronal dynamics associated with memory persistence remains to be identified10.”
From Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence (2014) · cites this paper as [10]
These data highlight the structural substrate by which midbrain-derived dopamine could modulate hippocampal dynamics.
“In line with earlier reports these data highlight the structural substrate by which midbrain-derived dopamine could modulate hippocampal dynamics10,15.”
From Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence (2014) · cites this paper as [10]
The VTA firing response to spatial novelty resulted in a higher fraction of action potentials discharged in bursts.
“This VTA firing response to spatial novelty, which might be partially informed by hippocampal spatio-contextual inputs10,16, resulted in a higher fraction of action potentials discharged in bursts (interspike interval<50ms; novelty-induced burst ratio change=0.31±0.07, t156=4.31, P=2.9×10−5, paired t-test), a potentially suitable signal to in turn modulate hippocampal dynamics.”
From Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence (2014) · cites this paper as [10]
Dopamine release depends on systems-level processes that include motivation and stimulus novelty.
“Importantly, the dopamine release depends on systems-level processes that include motivation and stimulus novelty [8]”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [8]
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- Authors
- Lisman, J. E., & Grace, A. A.
- Affiliations
- Brandeis University (US)
- University of Pittsburgh (US)
- Corresponding author
- Lisman, John E.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 46
- Issue
- 5
- Pages
- 703-713
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2121007598
- Cited by
- 1,983
- References
- 107
- Citations by year
- 2026: 105 · 2025: 97 · 2024: 139 · 2023: 97 · 2022: 99 · 2021: 115 · 2020: 122 · 2019: 92 · 2018: 97 · 2017: 93 · 2016: 97 · 2015: 120 · 2014: 103 · 2013: 103 · 2012: 96
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2968 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- W. M. Keck Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hippocampus, ventral tegmental area, dopamine, long-term memory consolidation, novelty detection, subiculum, ventral pallidum, accumbens, long-term potentiation, learning, salience, dopaminergic neurons
- MeSH terms
- Animals, Hippocampus, Humans, Memory, Nerve Net, Time Factors, Ventral Tegmental Area
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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