Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; Department of Molecular, Cell and Systems Biology, University of California Riverside, Riverside, CA 92521, USA.
Department of Molecular, Cell and Systems Biology, University of California Riverside, Riverside, CA 92521, USA.
Prog Neurobiol. 2023 Dec;231:102542. doi: 10.1016/j.pneurobio.2023.102542. Epub 2023 Oct 26.
Axo-axonic cells (AACs) provide specialized inhibition to the axon initial segment (AIS) of excitatory neurons and can regulate network output and synchrony. Although hippocampal dentate AACs are structurally altered in epilepsy, physiological analyses of dentate AACs are lacking. We demonstrate that parvalbumin neurons in the dentate molecular layer express PTHLH, an AAC marker, and exhibit morphology characteristic of AACs. Dentate AACs show high-frequency, non-adapting firing but lack persistent firing in the absence of input and have higher rheobase than basket cells suggesting that AACs can respond reliably to network activity. Early after pilocarpine-induced status epilepticus (SE), dentate AACs receive fewer spontaneous excitatory and inhibitory synaptic inputs and have significantly lower maximum firing frequency. Paired recordings and spatially localized optogenetic stimulation revealed that SE reduced the amplitude of unitary synaptic inputs from AACs to granule cells without altering reliability, short-term plasticity, or AIS GABA reversal potential. These changes compromised AAC-dependent shunting of granule cell firing in a multicompartmental model. These early post-SE changes in AAC physiology would limit their ability to receive and respond to input, undermining a critical brake on the dentate throughput during epileptogenesis.
轴突-轴突细胞 (AACs) 为兴奋性神经元的轴突起始段 (AIS) 提供专门的抑制作用，并可调节网络输出和同步性。尽管海马齿状回 AAC 在癫痫中结构发生改变，但对齿状回 AAC 的生理分析仍缺乏。我们证明齿状回分子层中的 parvalbumin 神经元表达 PTHLH，这是 AAC 的标志物，并表现出 AAC 的形态特征。齿状回 AAC 表现出高频、不适应的放电，但在没有输入的情况下缺乏持续放电，并且比 basket 细胞具有更高的 rheobase，这表明 AAC 可以可靠地响应网络活动。在匹鲁卡品诱导的癫痫持续状态 (SE) 后早期，齿状回 AAC 接收的自发性兴奋性和抑制性突触输入减少，最大放电频率显著降低。成对记录和空间局部光遗传学刺激显示，SE 降低了 AAC 到颗粒细胞的单位突触输入的幅度，而不改变可靠性、短期可塑性或 AIS GABA 反转电位。这些变化损害了颗粒细胞放电在多室模型中依赖 AAC 的分流。SE 后早期 AAC 生理学的这些变化将限制其接收和响应输入的能力，破坏癫痫发生过程中齿状回通量的关键制动。
