Vasnik Sonali, Sikdar Sujit K
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Acta Physiol (Oxf). 2021 Apr;231(4):e13603. doi: 10.1111/apha.13603. Epub 2021 Jan 1.
Acetylcholine release is vital in the pacing of theta rhythms in the hippocampus. The subiculum is the output region of the hippocampus with different neuronal subtypes that generate theta oscillations during arousal and rapid eye movement sleep. The combination of intrinsic resonance in the hippocampal neurons and the periodic excitation of hippocampal excitatory and inhibitory neurons by cholinergic pathway drives theta oscillations. However, the acetylcholine mediated effect on intrinsic subthreshold resonance generating hyperpolarization-activated cyclic nucleotide-gated current, I of subicular neurons is unexplored. We studied the acetylcholine receptor-independent effect of cholinergic agents on the intrinsic properties of subiculum principal neurons and the underlying mechanism.
We bath perfused acetylcholine or nicotine on rat brain slices in the presence of synaptic blockers. The physiological effect was studied by cholinergic fibres stimulation and electrophysiological recordings under whole-cell mode of subiculum neurons using septohippocampal sections.
Exogenously applied acetylcholine in the presence of atropine affected two groups of subicular neurons differently. Acetylcholine reduced the resonance frequency and I in bursting neurons, whereas these properties were unaffected in regular firing neurons. Subsequently, the endogenously released acetylcholine by stimulation showed a selective suppressive effect on I , sag, and resonance in burst firing among the two excitatory neurons. Nicotine suppressed the I amplitude in burst firing neurons, which was evident by decreased sag amplitude and resonance frequency and increased excitability.
Our study suggests cell type-specific acetylcholine receptor-independent shift in resonance frequency by partially inhibiting HCN current during high cholinergic inputs.
乙酰胆碱释放对海马体中θ节律的起搏至关重要。海马下托是海马体的输出区域，具有不同的神经元亚型，在觉醒和快速眼动睡眠期间产生θ振荡。海马神经元的内在共振与胆碱能通路对海马兴奋性和抑制性神经元的周期性兴奋相结合，驱动θ振荡。然而，乙酰胆碱对海马下托神经元产生超极化激活环核苷酸门控电流（Ih）的内在阈下共振的介导作用尚未得到探索。我们研究了胆碱能药物对海马下托主神经元内在特性的乙酰胆碱受体非依赖性作用及其潜在机制。
在存在突触阻滞剂的情况下，我们将乙酰胆碱或尼古丁灌注到大鼠脑片上。使用海马隔区切片，通过胆碱能纤维刺激和全细胞模式下海马下托神经元的电生理记录来研究其生理效应。
在存在阿托品的情况下，外源性应用乙酰胆碱对两组海马下托神经元的影响不同。乙酰胆碱降低了爆发性神经元的共振频率和Ih，而这些特性在规则放电神经元中未受影响。随后，通过刺激内源性释放的乙酰胆碱对两种兴奋性神经元中的爆发性放电的Ih、sag和共振表现出选择性抑制作用。尼古丁抑制了爆发性放电神经元中的Ih振幅，表现为sag振幅和共振频率降低以及兴奋性增加。
我们的研究表明，在高胆碱能输入期间，通过部分抑制超极化激活的环核苷酸门控通道（HCN）电流，乙酰胆碱受体非依赖性地使共振频率发生细胞类型特异性改变。
