Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

Besnard, Antoine; Miller, Shannon M.; Sahay, Amar

doi:10.1016/j.celrep.2020.01.055

Cited by 41 publications

(58 citation statements)

References 70 publications

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“…Further support for this theory comes from work looking at the role of the vHPC projection to the lateral septum (LS) in both reward and fear. A very recent study has shown that vCA3 projections to the dorsal LS suppress fear response (Besnard et al, 2020), similar to the function of vHPC projections to the LS in suppressing feeding (Sweeney and Yang, 2015). This is perhaps not too surprising as the HPC to septum projections (labeled as the Septal Hippocampus System or SHS) were central to Gray's theory of the behavioral inhibition system.…”

Section: Discussion: Overlap and Convergence In Anxiety Fear And Rementioning

confidence: 83%

“…Thus, the vHPC role in integrating fear-associated stimuli is at least in part through its projections to the PFC and amygdala. Furthermore, how intra-vHPC signaling impacts fear and aversion related behavior is still relatively unknown and distinct roles for vDG to vCA3 to vCA1 signaling in promoting fear response are just now being discovered (Besnard et al, 2020 ; Yeates et al, 2020 ).…”

Section: Vhpc As An Arbitrator Of Conflicting Stimulimentioning

confidence: 99%

“…Though the dHPC (A) and vHPC (B) share the same general micro circuitry, vCA1 and vSUB have more reciprocal connections and project to more cortical and subcortical structures than dCA1 and dSUB. ACC, anterior cingulate cortex; BLA, basolateral amygdala; BNST, bed nucleus of the stria terminalis; DLS, dorsolateral striatum; LHA, lateral hypothalamus; LS, lateral septum; NAcC, nucleus accumbens core; NAcS, nucleus accumbens shell; PFC, prefrontal cortex; RSC, retrosplenial cortex (Cenquizca and Swanson, 2007 ; Witter, 2007 ; McGinty et al, 2011 ; Arszovszki et al, 2014 ; Bienkowski et al, 2018 ; Besnard et al, 2020 ; Gergues et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Arbitration of Approach-Avoidance Conflict by Ventral Hippocampus

Bryant

Barker

2020

Front. Neurosci.

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When environmental cues or stimuli that represent both rewarding and aversive outcomes are presented, complex computations must be made in order to determine whether approach or avoidance is the better behavioral strategy. In many neuropsychiatric illnesses these computations can be skewed. In some instances, circumstances that may normally warrant avoidance instead promote approach, thus producing compulsive-like behavioral strategies that are inflexible in response to new or conflicting information. Alternatively, high sensitivity to aversion or low sensitivity to reward can result in the failure to achieve goals and loss of resilience that characterizes depressive disorders. Increases in compulsive-like behavior have been found to be associated with disrupted signaling in regions that regulate response to conflicting stimuli, including the hippocampus. Classic behavioral inhibition theories of hippocampus function in anxiety suggest that the hippocampus blocks aberrant behavior in response to anxiety related cues or stimuli. The hippocampus may act to block approach in the face of conflicting stimuli. Dysregulations of hippocampal function, as may be present in neuropsychiatric disorders, may therefore promote aberrant approach behavior. The ventral hippocampus (vHPC) subregion is key for coordinating this approach/avoidance conflict resolution, likely through its participation with cortico-striatal and mesolimbic circuits. We revisit Gray's behavioral inhibition theory of HPC function, first posited in the 1980s, and interpret in the context of new knowledge on vHPC function gained through modern technology. Taken together with the extant, classical literature on hippocampal function, we propose that these new findings suggest that vHPC circuits balance behavioral response to conflicting stimuli in a manner that is both state- and context-dependent and, further, that disruption of specific vHPC circuits tips the balance in favor of biased approach or avoidance behavioral strategies.

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Section: Discussion: Overlap and Convergence In Anxiety Fear And Rementioning

confidence: 83%

Section: Vhpc As An Arbitrator Of Conflicting Stimulimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Arbitration of Approach-Avoidance Conflict by Ventral Hippocampus

Bryant

Barker

2020

Front. Neurosci.

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“…The dysregulation of contextual fear processing may lead to pathological fear-related disorders such as PTSD, phobias, panic disorder and depression ( Maren et al, 2013 ; Parsons and Ressler, 2013 ). The hippocampus is thought to be critical in the formation of contextual fear memory ( Bast et al, 2003 ; Besnard et al, 2020 ; Daumas et al, 2005 ; Maren, 2001 ; Maren et al, 2013 ). Hippocampal pyramidal neurons and interneurons have received much attention related to the contextual fear memory process in the mammalian brain ( Lamsa and Lau, 2019 ; Roy et al, 2017 ; Xia et al, 2017 ; Zhu et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Activation of astrocytes in hippocampus decreases fear memory through adenosine A1 receptors

et al. 2020

eLife

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Astrocytes respond to and regulate neuronal activity, yet their role in mammalian behavior remains incompletely understood. Especially unclear is whether, and if so how, astrocyte activity regulates contextual fear memory, the dysregulation of which leads to pathological fear-related disorders. We generated GFAP-ChR2-EYFP rats to allow the specific activation of astrocytes in vivo by optogenetics. We found that after memory acquisition within a temporal window, astrocyte activation disrupted memory consolidation and persistently decreased contextual but not cued fear memory accompanied by reduced fear-related anxiety behavior. In vivo microdialysis experiments showed astrocyte photoactivation increased extracellular ATP and adenosine concentrations. Intracerebral blockade of adenosine A1 receptors (A1Rs) reversed the attenuation of fear memory. Furthermore, intracerebral or intraperitoneal injection of A1R agonist mimicked the effects of astrocyte activation. Therefore, our findings provide a deeper understanding of the astrocyte-mediated regulation of fear memory, and suggest a new and important therapeutic strategy against pathological fear-related disorders.

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“…Additionally, we found that optogenetic inhibition of dHPC projections to the LS during contextual 248 fear retrieval/expression disrupted fear memory performance, indicating the importance of this 249 dHPC-to-LS pathway in memory expression as well, corroborating with earlier studies (Olton et 250 al., 1978, Besnard et al, 2020. Together, our results suggest that the dHPC-to-LS pathway is 251 critical for both memory acquisition and expression.…”

Section: Dhpc-to-ls Pathway Is Critical For Memory Acquisition and Exmentioning

confidence: 67%

Hippocampal efferents to retrosplenial cortex and lateral septum are required for memory acquisition

Opalka

Wang

2020

Preprint

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Learning and memory involves a large neural network of many brain regions, including the notable hippocampus along with the retrosplenial cortex (RSC) and lateral septum (LS). Previous studies have established that the dorsal hippocampus (dHPC) plays a critical role during the acquisition and expression of episodic memories. However, the role of downstream circuitry from the dHPC, including the dHPC-to-RSC and dHPC-to-LS pathways, has come under scrutiny only recently. Here, we employed an optogenetic approach with contextual fear conditioning in mice to determine whether the above two pathways are involved in acquisition and expression of contextual fear memory. We found that a selective inhibition of the dHPC neuronal terminals in either the RSC or LS during acquisition impaired subsequent memory performance, suggesting that both the dHPC-to-RSC and dHPC-to-LS pathways play a critical role in memory acquisition. We also selectively inhibited the two dHPC efferent pathways during memory expression and found a differential effect on memory performance. These results indicate the intricacies of memory processing and that hippocampal efferents to cortical and subcortical regions may be differentially involved in aspects of physiological and cognitive memory processes.

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Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

Cited by 41 publications

References 70 publications

Arbitration of Approach-Avoidance Conflict by Ventral Hippocampus

Arbitration of Approach-Avoidance Conflict by Ventral Hippocampus

Activation of astrocytes in hippocampus decreases fear memory through adenosine A1 receptors

Hippocampal efferents to retrosplenial cortex and lateral septum are required for memory acquisition

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