A Hippocampus-Accumbens Tripartite Neuronal Motif Guides Appetitive Memory in Space

Trouche, Stéphanie; Koren, Vadim; Doig, Natalie M.; Ellender, Tommas J.; El-Gaby, Mohamady; Lopes‐dos‐Santos, Vítor; Reeve, Hayley M.; Perestenko, Pavel V.; Garas, Farid N.; Magill, Peter J.; Sharott, Andrew; Dupret, David

doi:10.1016/j.cell.2018.12.037

Cited by 121 publications

(148 citation statements)

References 38 publications

(67 reference statements)

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“…Together, this division of labor along the septotemporal axis of the HC in rodents is thought to calibrate adaptive fear responses or defensive behavior, such as immobility (high levels of freezing behavior) when threat is certain (e.g., context associated with a mild footshock) and increased mobility (low levels of freezing behavior) to ambiguous, non-threatening stimuli in the environment (e.g., a similar neutral context not associated with a footshock). However, the dHC and vHC have different efferent connectivity: the dHC projects to the mammillary bodies (MB), nucleus accumbens (Trouche et al, 2019), anterior thalamic nuclei, and dorsolateral septum (DLS) nuclei, whereas the vHC sends monosynaptic projections to amygdala, nucleus accumbens, prefrontal cortex, hypothalamus, and DLS (Fanselow and Dong, 2010;Strange et al, 2014). Consequently, a fundamental question that arises is how information pertaining to certain and ambiguous contextual threats computed in the dHC and vHC is integrated and relayed to extrahippocampal circuits to calibrate fear responses.…”

Section: Introductionmentioning

confidence: 99%

Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

2020

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Considerable work emphasizes a role for hippocampal circuits in governing contextual fear discrimination. However, the intra-and extrahippocampal pathways that route contextual information to cortical and subcortical circuits to guide adaptive behavioral responses are poorly understood. Using terminal-specific optogenetic silencing in a contextual fear discrimination learning paradigm, we identify opposing roles for dorsal CA3-CA1 (dCA3-dCA1) projections and dorsal CA3-dorsolateral septum (dCA3-DLS) projections in calibrating fear responses to certain and ambiguous contextual threats, respectively. Ventral CA3-DLS (vCA3-DLS) projections suppress fear responses in both certain and ambiguous contexts, whereas ventral CA3-CA1 (vCA3-vCA1) projections promote fear responses in both these contexts. Lastly, using retrograde monosynaptic tracing, ex vivo electrophysiological recordings, and optogenetics, we identify a sparse population of DLS parvalbumin (PV) neurons as putative relays of dCA3-DLS projections to diverse subcortical circuits. Taken together, these studies illuminate how distinct dCA3 and vCA3 outputs calibrate contextual fear discrimination.

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Section: Introductionmentioning

confidence: 99%

Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

2020

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“…We found that FS-neurons in the NAc had reduced firing rates after tamoxifen administration and this correlated with a decrease in local theta power. In the NAc area, FS interneurons modulate principal neurons through its powerful and sustained feedforward inhibition [40,41]. PV expressing interneurons, which constitute 1-2% of NAc neurons, have particular firing properties and are classified as FS-neurons [40,42].…”

Section: Discussionmentioning

confidence: 99%

Parvalbumin interneurons in the nucleus accumbens regulate impairment of risk avoidance inDISC1transgenic mice

Zhou

Wu²,

Xiao

et al. 2020

Preprint

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One strong survival instinct in animals is to approach things that are of benefit and avoid risk. In humans, a large portion of mental disorders are accompanied by cognition-related impairments including the inability to recognize potential risks. One of the most important genes involved in risk behavior is disrupted-in-schizophrenia-1 (DISC1), and animal models where this gene has some dysfunction show cognitive impairments. However, whether DISC1 mice models have an impairment in avoiding potential risks is still not fully understood. In the present study, we used DISC1-N terminal truncation (DISC1-NTM) mice to study cognitive abilities related to potential risks. We found that DISC1-NTM mice were impaired in risk avoidance on the elevated plus maze (EPM) test, and showed impairment in social preference in a three-chamber social interaction test. Staining for c-Fos following the EPM indicated that the nucleus accumbens (NAc) was associated with risk avoidance behavior in DISC1-NTM mice. Meanwhile, in vivo electrophysiological recordings showed that firing rates of fast spiking neurons (FS) in the NAc significantly decreased in DISC1-NTM mice following tamoxifen administration. In addition, theta band power was lower when mice shuttled from the safe (closed) arms to the risky (open) arms, an effect which disappeared after induction of the truncated DISC1 gene. Furthermore, we found through in vitro patch clamp recording that the frequency of action potentials stimulated by current injection was lower in parvalbumin (PV) neurons in the NAc of DISC1-NTM mice than their wild-type littermates. Risk-avoidance impairments in DISC1-NTM mice were rescued using optogenetic tools that activated NAcPV neurons. Finally, we inhibited activitiy of NAcPV neurons in PV-Cre mice, which mimicked the risk-avoidance impairment found in the DISC1-NTM mice during tests on the elevated zero maze. Taken together, our findings confirmed a cognitive impairment in DISC1-NTM mice related to risk recognition and suggests that reduced excitability of NAcPV neurons may be responsible.

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“…Importantly, it is 7 also unknown whether dSWRs and vSWRs engage similar or contrasting NAc populations. To 8 sample the respective target regions of the sparse dH projection and the much more prominent 9 vH projection [6][7][8][9][10]12 , we recorded from both the NAc core and medial shell (Extended Data Fig. 10 1d).…”

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confidence: 99%

“…3 6c,d). As individual FSIs innervate large populations of MSNs 22 , FSIs may play an important 4 role in coordinating NAc responses to hippocampal inputs 7 . We also found that SWR-5 modulation of both MSNs and FSIs was anatomically distributed in a pattern consistent with 6 reported dH and vH projections to the NAc [6][7][8][9][10]12 , with V+ neurons present in both the medial 7…”

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confidence: 99%

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Dorsal and ventral hippocampus engage opposing networks in the nucleus accumbens

Sosa

Joo

Frank

2019

Preprint

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2Memories of positive experiences require the brain to link places, events, and reward outcomes. 3Neural processing underlying the association of spatial experiences with reward is thought to 4 depend on interactions between the hippocampus and the nucleus accumbens (NAc) 1-9 . 5Hippocampal projections to the NAc arise from both the ventral hippocampus (vH) and the 6 dorsal hippocampus (dH) 6-12 , and studies using optogenetic interventions have demonstrated that 7 either vH 5,6 or dH 7 input to the NAc can support behaviors dependent on spatial-reward 8 associations. It remains unclear, however, whether dH, vH, or both coordinate memory 9processing of spatial-reward information in the hippocampal-NAc circuit under normal 10 conditions. Times of memory reactivation within and outside the hippocampus are marked by 11 hippocampal sharp-wave ripples (SWRs) [13][14][15][16][17][18][19] , discrete events which facilitate investigation of 12 inter-regional information processing. It is unknown whether dH and vH SWRs act in concert or 13 separately to engage NAc neuronal networks, and whether either dH or vH SWRs are 14 preferentially linked to spatial-reward representations. Here we show that dH and vH SWRs 15 occur asynchronously in the awake state and that NAc spatial-reward representations are 16 selectively activated during dH SWRs. We performed simultaneous extracellular recordings in 17 the dH, vH, and NAc of rats learning and performing an appetitive spatial task and during 18 sleep. We found that individual NAc neurons activated during SWRs from one subdivision of 19 the hippocampus were typically suppressed or unmodulated during SWRs from the other. NAc 20 neurons activated during dH versus vH SWRs showed markedly different task-related firing 21 patterns. Only dH SWR-activated neurons were tuned to similarities across spatial paths and past 22 reward, indicating a specialization for the dH-NAc, but not vH-NAc, network in linking reward 23 to discrete spatial paths. These temporally and anatomically separable hippocampal-NAc 24 interactions suggest that dH and vH coordinate opposing channels of mnemonic processing in 25 the NAc. 26

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A Hippocampus-Accumbens Tripartite Neuronal Motif Guides Appetitive Memory in Space

Cited by 121 publications

References 38 publications

Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

Parvalbumin interneurons in the nucleus accumbens regulate impairment of risk avoidance inDISC1transgenic mice

Dorsal and ventral hippocampus engage opposing networks in the nucleus accumbens

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