A ventral CA1 to nucleus accumbens core engram circuit mediates conditioned place preference for cocaine

Zhou, Yiming; Zhu, Huiwen; Liu, Zhiyuan; Chen, Xi; Su, Xiujuan; Ma, Chunyang; Tian, Zhenfu; Bing, Huang; Yan, Enhui; Liu, Xing; Ma, Lan

doi:10.1038/s41593-019-0524-y

Cited by 118 publications

(101 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we tested the hypothesis that contextual fear learning involves strengthening of functionally defined synapses, which connect context-encoding hippocampal CA1 neurons to a subset of neurons in the amygdala. The conventional approaches examining randomly selected synapses do not allow the efficient detection of associative learning-induced synaptic changes because associative memory is encoded sparsely in a subset of synapses 7,19,20,25,27 , and functional heterogeneity exists in brain areas orchestrating emotional learning and memory [28][29][30] . We recently developed an innovative approach by combining neural activity-dependent labeling 31 , optogenetic, and electrophysiological techniques, enabling efficient detection of synaptic changes in associative learning 7 .…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the input specificity of LTP could confer the selectivity of contextual fear memory, enabling adaptive fear responses only to the relevant context, together with a well-documented role of the medial prefrontal cortex (mPFC) 40 . Therefore, the input specificity of synaptic potentiation may serve as the universal mechanism for selective fear responses to a context or sensory cue that predicts danger 7,19,20,25 .…”

Section: Discussionmentioning

confidence: 99%

“…j NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-15121-2 ARTICLE context-dependent expression of extinguished fear memory for an auditory cue 4,46 . Moreover, vCA1 neurons projecting to the nucleus accumbens play a role in social memory 47 , goal-directed behaviors 28 , and conditioned place preference for cocaine 20 . Previous studies also implicate granule cells in the ventral dentate gyrus and vCA1 neurons projecting to the lateral hypothalamus in innate anxiety and avoidance behavior 14,48 .…”

Section: Discussionmentioning

confidence: 99%

“…4f). Synaptic plasticity for fear memory formation may be induced preferentially in synapses consisting of presynaptic vCA1 inputs and postsynaptic BA neurons that are activated during contextual fear conditioning 7,19,20 . To test this possibility, vCA1 neurons active in Context A were labeled with ChR2 during context labeling sessions, whereas BA neurons active during contextual fear conditioning were labeled with tdTomato (tdT) in Fos-CreER T2 × ROSA-LSL-tdTomato mice ( Fig.…”

Section: Articlementioning

confidence: 99%

See 3 more Smart Citations

Encoding of contextual fear memory in hippocampal–amygdala circuit

2020

View full text Add to dashboard Cite

In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal-amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1-BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and synaptic potentiation in the vCA1-BA pathway. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Articlementioning

confidence: 99%

See 2 more Smart Citations

Encoding of contextual fear memory in hippocampal–amygdala circuit

2020

View full text Add to dashboard Cite

show abstract

“…Pathwayspecific activation of these glutamate inputs to the Acb has been demonstrated to trigger different physiological responses (Goto and Grace, 2008;Sesack and Grace, 2010), while their roles in drug memory storage are largely unknown. In our previous study, we found that the preferential synaptic strengthening of the vCA1-AcbC engram circuit evoked by cocaine conditioning mediated the cocaine-CPP memory storage (Zhou et al, 2019). However, the essential circuits, such as vCA1-AcbC and mPFC-AcbC circuits, involved in environmental cue-induced retrieval of drug memory remain unclear.…”

Section: Introductionmentioning

confidence: 95%

The Projection From Ventral CA1, Not Prefrontal Cortex, to Nucleus Accumbens Core Mediates Recent Memory Retrieval of Cocaine-Conditioned Place Preference

Zhou

Yan

Cheng

et al. 2020

Front. Behav. Neurosci.

Self Cite

View full text Add to dashboard Cite

Drug-paired cues inducing memory retrieval by expressing drug-seeking behaviors present a major challenge to drug abstinence. How neural circuits coordinate for drug memory retrieval remains unclear. Here, we report that exposure of the training chamber where cocaine-conditioned place preference (CPP) was performed increased neuronal activity in the core of nucleus accumbens (AcbC), ventral CA1 (vCA1), and medial prefrontal cortex (mPFC), as shown by elevated pERK and c-Fos levels. Chemogenetic inhibition of neuronal activity in the vCA1 and AcbC, but not mPFC, reduced the time spent in the cocaine-paired compartment, suggesting that the vCA1 and AcbC are required for the retrieval of cocaine-CPP memory and are key nodes recruited for cocaine memory storage. Furthermore, chemogenetic inhibition of the AcbC-projecting vCA1 neurons, but not the AcbC-projecting mPFC neurons, decreased the expression of cocaine-CPP. Optogenetic inhibition of the vCA1–AcbC projection, but not the mPFC–AcbC projection, also reduced the preference for the cocaine-paired compartment. Taken together, the cue-induced natural recall of cocaine memory depends on vCA1–AcbC circuits. The connectivity from the vCA1 to the AcbC may store the information of the cue–cocaine reward association critically required for memory retrieval. These data thus provide insights into the neural circuit basis of retrieval of drug-related memory.

show abstract

AMPA and NMDA receptors in dentate gyrus mediate memory for sucrose in two port discrimination task

Sagarkar,

Bhat,

Rotti

et al. 2024

Hippocampus

View full text Add to dashboard Cite

Although the phenomenon of memory formation and recall associated with the use of psychotropic drugs has been extensively studied, mechanisms underlying memories for natural reward have not been clarified. Herein, we test the hypothesis that glutamatergic receptors in the dentate gyrus play a role in memories associated with sucrose. We used pellet self‐administration protocol to generate memories in two‐port nose‐poke discrimination task using male Wistar rats. During non‐rewarded probe trial, the conditioned animals readily discriminated the active port versus inactive port and showed massive increase in mRNA expression of AMPA receptor subunit genes (gria2, gria3) as well as c‐Fos protein in the DG. Access to sweet pellet further enhanced c‐Fos expression in the DG. However, animals pre‐treated with AMPA receptor antagonist CNQX (intra‐DG), on exposure to operant chamber (no pellet), showed decreased discrimination as well as c‐Fos expression. We suggest that AMPA receptors in DG mediate recall and consolidation of memories associated with sucrose consumption. CNQX pre‐treated animals, if presented with sweet pellet on nose poke, exhibited high discrimination index coupled with increased c‐Fos expression. In these CNQX treated rats, the DI was again decreased following administration of NMDA receptor antagonist AP5. We suggest that, although AMPA receptors are blocked, the access to sweet pellet may induce surge of glutamate in the DG, which in turn may reinstate memories via activation of erstwhile silent synapses in NMDA dependant manner.

show abstract

A ventral CA1 to nucleus accumbens core engram circuit mediates conditioned place preference for cocaine

Cited by 118 publications

References 57 publications

Encoding of contextual fear memory in hippocampal–amygdala circuit

Encoding of contextual fear memory in hippocampal–amygdala circuit

The Projection From Ventral CA1, Not Prefrontal Cortex, to Nucleus Accumbens Core Mediates Recent Memory Retrieval of Cocaine-Conditioned Place Preference

AMPA and NMDA receptors in dentate gyrus mediate memory for sucrose in two port discrimination task

Contact Info

Product

Resources

About