The role of subcortical inputs to the hippocampal CA3 region in fear memory

海马 CA3 区皮层下输入在恐惧记忆中的作用

基本信息

  • 批准号:
    10582830
  • 负责人:
  • 金额:
    $ 39.53万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-01-01 至 2027-10-31
  • 项目状态:
    未结题

项目摘要

PROJECT ABSTRACT The hippocampus is essential for memory formation and spatial navigation. In the classic hippocampal trisynaptic circuit (entorhinal cortex→dentate gyrus→CA3→CA1), dentate gyrus and CA1 act as the primary input and output areas, respectively, that connect the hippocampus with the brain areas outside of the hippocampus. By contrast, CA3 is often viewed as an auto-associative network vital for contextual learning via its intra-hippocampal connections. While CA3’s intra-hippocampal inputs and outputs, including mossy fibers from dentate gyrus, recurrent collaterals from CA3, and Schaffer collaterals to CA1 have been extensively studied, the connections between CA3 and other subcortical areas remain largely unexplored. This proposal aims to fill this critical gap of knowledge by investigating the functional connectivity and behavioral roles of subcortical-to-CA3 inputs. Our preliminary experiments revealed that two subcortical areas outside of the hippocampus – basolateral amygdala and supramammillary nucleus in the hypothalamus – excite and inhibit CA3 pyramidal neuron activity, respectively. We will, therefore, test a central hypothesis that basolateral amygdala and supramammillary nucleus promote and suppress contextual fear learning by enhancing and suppressing the activity of CA3 pyramidal neurons, respectively. In Aims 1 and 2, we will determine whether a selective population of neurons in basolateral amygdala and supramammillary nucleus excite and inhibit CA3 pyramidal neuron activity in vitro and in vivo, respectively. In Aim 3, we will determine the role of basolateral amygdala-CA3 and supramammillary nucleus-CA3 inputs in contextual fear memory. The proposed studies represent a significant shift of focus from traditional research on CA3’s intra-hippocampal connectivity to its extra-hippocampal connectivity. Furthermore, as impairments of CA3, basolateral amygdala, and supramammillary nucleus are strongly associated with many neuropsychiatric disorders, including posttraumatic stress disorders (PTSD), depression, chronic stress and epilepsy, this proposal will provide a valuable knowledge base for future studies to explore the role of these three interconnected regions in disease.
项目摘要

项目成果

期刊论文数量(0)
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科研奖励数量(0)
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Qian Sun其他文献

Qian Sun的其他文献

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{{ truncateString('Qian Sun', 18)}}的其他基金

Long-range GABAergic inhibition coordinates hippocampal-subcortical circuit activity in memory formation
长程 GABA 能抑制协调记忆形成中的海马-皮层下回路活动
  • 批准号:
    10658072
  • 财政年份:
    2023
  • 资助金额:
    $ 39.53万
  • 项目类别:
Dorsoventral functional divergence of the hippocampal CA3 circuit
海马 CA3 回路的背腹功能分歧
  • 批准号:
    10406500
  • 财政年份:
    2021
  • 资助金额:
    $ 39.53万
  • 项目类别:
Dorsoventral functional divergence of the hippocampal CA3 circuit
海马 CA3 回路的背腹功能分歧
  • 批准号:
    9932690
  • 财政年份:
    2019
  • 资助金额:
    $ 39.53万
  • 项目类别:
Dorsoventral functional divergence of the hippocampal CA3 circuit
海马 CA3 回路的背腹功能分歧
  • 批准号:
    9760000
  • 财政年份:
    2019
  • 资助金额:
    $ 39.53万
  • 项目类别:

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