The role of CA2 in epilepsy and social comorbidity

CA2 在癫痫和社会共病中的作用

基本信息

项目摘要

PROJECT ABSTRACT A key challenge in temporal lobe epilepsy (TLE) is to determine the neural mechanisms contributing to seizures because current drugs fail to treat all seizures and usually come with debilitating side effects. Moreover, current drugs do not treat alterations in social behavior often manifest by individuals with epilepsy, including increased social aggression. This project will challenge current dogma as to the pathophysiological bases of how the hippocampus contributes to seizures in TLE, which has focused on three major regions of the hippocampus: dentate gyrus, CA3 and CA1. Instead, we examine area CA2, a relatively small region of hippocampus that has received little attention but is known to survive relatively intact in TLE patients and rodent models, and may serve as a seizure focus or facilitate seizure propagation. Experimental tools developed in the laboratories of the two Principal Investigators now enable the direct investigation of the importance of CA2 in mouse TLE models by employing a mouse line that expresses Cre recombinase relatively selectively in CA2 principal neurons. Cre-dependent viral vectors will be used to express genetically encoded tools in CA2 principal neurons to examine both alterations in CA2 circuitry in TLE and the effects of CA2 acute or chronic silencing on seizures. Thus, we will determine whether CA2 controls the pharmacological induction of acute seizures in the healthy brain and/or chronic seizures in the epileptic brain. We will also determine the importance of CA2 in reported deficits in social cognition and social aggression in mouse models of acquired TLE, as we find that CA2 is required for social recognition memory and is implicated in social aggression. As the social hormone arginine vasopressin promotes social memory and social aggression by enhancing CA2 input and output, and has been shown to regulate seizures in animals, we will examine the role of CA2 regulation by this hormone on social behavioral alterations in epileptic mice. By evaluating the role of CA2 in epilepsy, this project offers the promise of providing both basic mechanistic insight into seizures and social behavioral comorbidity, and may validate novel drug targets highly enriched in CA2 neurons.
项目摘要

项目成果

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STEVEN A SIEGELBAUM其他文献

STEVEN A SIEGELBAUM的其他文献

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{{ truncateString('STEVEN A SIEGELBAUM', 18)}}的其他基金

Role of HCN1 Channels in the Function and Malfunction of Parvalbumin Positive Interneurons
HCN1 通道在小清蛋白阳性中间神经元功能和故障中的作用
  • 批准号:
    10609915
  • 财政年份:
    2021
  • 资助金额:
    $ 52.76万
  • 项目类别:
Role of HCN1 channels in the function and malfunction of parvalbumin positive interneurons
HCN1通道在小清蛋白阳性中间神经元功能和故障中的作用
  • 批准号:
    10279148
  • 财政年份:
    2021
  • 资助金额:
    $ 52.76万
  • 项目类别:
Hippocampal CA2 sharp wave ripple oscillations in neuropsychiatric disease
神经精神疾病中海马 CA2 尖波波纹振荡
  • 批准号:
    10536654
  • 财政年份:
    2021
  • 资助金额:
    $ 52.76万
  • 项目类别:
Role of HCN1 channels in the function and malfunction of parvalbumin positive interneurons
HCN1通道在小清蛋白阳性中间神经元功能和故障中的作用
  • 批准号:
    10448515
  • 财政年份:
    2021
  • 资助金额:
    $ 52.76万
  • 项目类别:
Hippocampal CA2 sharp wave ripple oscillations in neuropsychiatric disease
神经精神疾病中海马 CA2 尖波波纹振荡
  • 批准号:
    10345498
  • 财政年份:
    2021
  • 资助金额:
    $ 52.76万
  • 项目类别:
Regulation of social aggression through hippocampal CA2 inputs to lateral septum
通过海马 CA2 输入至外侧隔膜调节社会攻击行为
  • 批准号:
    10002290
  • 财政年份:
    2019
  • 资助金额:
    $ 52.76万
  • 项目类别:
Regulation of social aggression through hippocampal CA2 inputs to lateral septum
通过海马 CA2 输入至外侧隔膜调节社会攻击行为
  • 批准号:
    10226105
  • 财政年份:
    2019
  • 资助金额:
    $ 52.76万
  • 项目类别:
Regulation of social aggression through hippocampal CA2 inputs to lateral septum
通过海马 CA2 输入至外侧隔膜调节社会攻击行为
  • 批准号:
    10413193
  • 财政年份:
    2019
  • 资助金额:
    $ 52.76万
  • 项目类别:
Regulation of social aggression through hippocampal CA2 inputs to lateral septum
通过海马 CA2 输入至外侧隔膜调节社会攻击行为
  • 批准号:
    10652333
  • 财政年份:
    2019
  • 资助金额:
    $ 52.76万
  • 项目类别:
The role of the hippocampal CA2 region in neuropsychiatric disease
海马CA2区在神经精神疾病中的作用
  • 批准号:
    9195134
  • 财政年份:
    2015
  • 资助金额:
    $ 52.76万
  • 项目类别:

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