title: Synaptic Targeting of Double-Projecting Ventral CA1 Hippocampal Neurons to the Medial Prefrontal Cortex and Basal Amygdala.
abstract: The acquisition and retrieval of contextual fear memory requires coordinated neural activity in the hippocampus, medial prefrontal cortex (mPFC), and amygdala. The contextual information encoded in the hippocampus is conveyed to the mPFC and amygdala for contextual fear conditioning. Previous studies have suggested that a CA1 neuronal population in the ventral hippocampus (VH) projects to both the mPFC and amygdala and is recruited in context-dependent control of conditioned fear. However, how double-projecting ventral CA1 hippocampal (vCA1) neurons modulate the activity of the mPFC and amygdala at the synaptic level has not been determined previously. Here, we show that the optogenetic silencing of the VH prevented the recall of contextual fear memory in mice, indicating its role in contextual fear expression. In dual retrograde viral tracing and c-Fos immunostaining experiments, we found that a proportion of vCA1 neurons projected to both the mPFC and amygdala and were recruited preferentially during context exposure, suggesting their role in encoding context representations. Moreover, optogenetic stimulation of axon collaterals of double-projecting vCA1 neurons induced monosynaptic excitatory responses in both the mPFC and basal amygdala, indicating that they could convey contextual information through the VH-mPFC and VH-amygdala pathways. The activation of double-projecting vCA1 neurons also induced action potential firings in the mPFC neurons that project to the amygdala, suggesting that they can also activate the VH-mPFC-amygdala pathway. With these synaptic mechanisms, double-projecting vCA1 neurons could induce synchronized neural activity in the mPFC and amygdala and convey contextual information efficiently to the basal amygdala for contextual fear conditioning.SIGNIFICANCE STATEMENTThis work demonstrates that ventral CA1 hippocampal (vCA1) neurons projecting to both the medial prefrontal cortex (mPFC) and amygdala are activated preferentially when contextual information is processed in the ventral hippocampus, which is required for contextual fear expression. Our electrophysiological experiments reveal that the activation of double-projecting vCA1 neurons induces excitatory synaptic activity in both the mPFC and amygdala. These results suggest that double-projecting vCA1 neurons could contribute to contextual fear responses by inducing synchronized activity in the mPFC and amygdala and conveying contextual information to the basal amygdala more efficiently than vCA1 neurons projecting to either the mPFC or amygdala alone. These findings provide important insights into the mechanisms of the acquisition and retrieval of contextual fear memory.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521.
authors.forename: Woong Bin
authors.identifier: 0000-0001-5251-6373
authors.initials: WB
authors.lastname: Kim
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521 juncho@ucr.edu.
authors.forename: Jun-Hyeong
authors.identifier: 0000-0002-6844-3583
authors.initials: JH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000166:cytology / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
keywords: amygdala; fear conditioning; hippocampus; learning and memory; mPFC