Cell-type- and subregion-specific basolateral amygdala inputs to ventral CA1–subiculum

The hippocampus is essential for learning and memory and interacts extensively with cortical and subcortical regions. Although the heterogeneity of intrinsic connectivity of hippocampal neurons is well established, the diversity of its extrahippocampal connectivity remains less understood. Such differential connectivity may contribute to functional diversity of hippocampal neurons in specific positions. Ventral CA1 (vCA1) and ventral subiculum (vSub) form strong reciprocal connections with the basolateral amygdala (BLA), a region critical for emotional and social regulation. Consequently, BLA–vCA1–vSub circuits have been implicated in anxiety-related and social behaviors. However, the functional connectivity from BLA to vCA1–vSub at the cellular and circuit levels is underexplored. To address this, we combined viral tracing with Channelrhodopsin-2 (ChR2)–assisted slice electrophysiology to examine BLA projections to vCA1–vSub in mice of either sex. We found that BLA inputs are not uniformly distributed along the transverse axis in vCA1-vSub. Instead, BLA selectively excites pyramidal neurons in distal vCA1–vSub while largely avoiding proximal vCA1 near CA2. BLA terminals strongly excited parvalbumin-expressing interneurons but only weakly recruited a small subset of somatostatin-expressing interneurons, generating robust disynaptic inhibitory synaptic currents in pyramidal neurons. Additionally, the same distal pyramidal neurons that receive BLA excitation also project back to the BLA. These findings reveal that BLA establishes cell-type- and subregion-specific excitatory connections within vCA1–vSub, highlighting a circuit architecture that may underlie functional heterogeneity in ventral hippocampal processing. Significance statement The hippocampus interacts extensively with cortical and subcortical regions, yet how long-range extrahippocampal inputs are organized across hippocampal subregions remains poorly understood. We examined projections from the basolateral amygdala (BLA) to the ventral hippocampus and found that BLA inputs selectively excite pyramidal neurons in distal ventral CA1 and ventral subiculum while largely avoiding proximal ventral CA1. BLA projections preferentially excite parvalbumin-expressing interneurons, provide disynaptic inhibition onto pyramidal neurons, and are reciprocally connected with the same pyramidal neurons in ventral CA1 and subiculum they excite. These findings reveal a highly selective connectivity pattern of amygdala–hippocampal circuits, providing a circuit framework for understanding how emotional information is routed through distinct ventral hippocampal pathways.

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Publication Details

Journal
Journal of Neuroscience
Published
2026-11-06
DOI
https://doi.org/10.1523/jneurosci.1041-26.2026
Primary Topic
Memory and Neural Mechanisms
Type
article
Field-Weighted Citation Impact
0.00

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article

Cell-type- and subregion-specific basolateral amygdala inputs to ventral CA1–subiculum

Li Minghua, Wanyi Guo, Yu-Qiu Jiang, Qian Sun (孙钱)
1 links
Journal of Neuroscience
Memory and Neural Mechanisms
article

Cell-type- and subregion-specific basolateral amygdala inputs to ventral CA1–subiculum

Li Minghua, Wanyi Guo, Yu-Qiu Jiang, Qian Sun (孙钱)
article en

Abstract

The hippocampus is essential for learning and memory and interacts extensively with cortical and subcortical regions. Although the heterogeneity of intrinsic connectivity of hippocampal neurons is well established, the diversity of its extrahippocampal connectivity remains less understood. Such differential connectivity may contribute to functional diversity of hippocampal neurons in specific positions. Ventral CA1 (vCA1) and ventral subiculum (vSub) form strong reciprocal connections with the basolateral amygdala (BLA), a region critical for emotional and social regulation. Consequently, BLA–vCA1–vSub circuits have been implicated in anxiety-related and social behaviors. However, the functional connectivity from BLA to vCA1–vSub at the cellular and circuit levels is underexplored. To address this, we combined viral tracing with Channelrhodopsin-2 (ChR2)–assisted slice electrophysiology to examine BLA projections to vCA1–vSub in mice of either sex. We found that BLA inputs are not uniformly distributed along the transverse axis in vCA1-vSub. Instead, BLA selectively excites pyramidal neurons in distal vCA1–vSub while largely avoiding proximal vCA1 near CA2. BLA terminals strongly excited parvalbumin-expressing interneurons but only weakly recruited a small subset of somatostatin-expressing interneurons, generating robust disynaptic inhibitory synaptic currents in pyramidal neurons. Additionally, the same distal pyramidal neurons that receive BLA excitation also project back to the BLA. These findings reveal that BLA establishes cell-type- and subregion-specific excitatory connections within vCA1–vSub, highlighting a circuit architecture that may underlie functional heterogeneity in ventral hippocampal processing. Significance statement The hippocampus interacts extensively with cortical and subcortical regions, yet how long-range extrahippocampal inputs are organized across hippocampal subregions remains poorly understood. We examined projections from the basolateral amygdala (BLA) to the ventral hippocampus and found that BLA inputs selectively excite pyramidal neurons in distal ventral CA1 and ventral subiculum while largely avoiding proximal ventral CA1. BLA projections preferentially excite parvalbumin-expressing interneurons, provide disynaptic inhibition onto pyramidal neurons, and are reciprocally connected with the same pyramidal neurons in ventral CA1 and subiculum they excite. These findings reveal a highly selective connectivity pattern of amygdala–hippocampal circuits, providing a circuit framework for understanding how emotional information is routed through distinct ventral hippocampal pathways.

Journal of Neuroscience
Case Western Reserve University (US)
National Institute of Mental Health
Openalex Percentile: Top 19%
Memory and Neural Mechanisms
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