Asynchronous Cholinergic Drive Correlates with Excitation-Inhibition Imbalance via a Neuronal Ca2+ Sensor Protein

作者：Zhou Keming; Cherra Salvatore J III; Goncharov Alexandr; Jin Yishi^*

来源：Cell Reports, 2017, 19(6): 1117-1129.

DOI：10.1016/j.celrep.2017.04.043

Excitation-inhibition imbalance in neural networks is widely linked to neurological and neuropsychiatric disorders. However, how genetic factors alter neuronal activity, leading to excitation-inhibition imbalance, remains unclear. Here, using the C. elegans locomotor circuit, we examine how altering neuronal activity for varying time periods affects synaptic release pattern and animal behavior. We show that while short-duration activation of excitatory cholinergic neurons elicits a reversible enhancement of presynaptic strength, persistent activation results to asynchronous and reduced cholinergic drive, inducing imbalance between endogenous excitation and inhibition. We find that the neuronal calcium sensor protein NCS-2 is required for asynchronous cholinergic release in an activity-dependent manner and dampens excitability of inhibitory neurons non-cell autonomously. The function of NCS-2 requires its Ca2+ binding and membrane association domains. These results reveal a synaptic mechanism implicating asynchronous release in regulation of excitation-inhibition balance.

• 出版日期2017-5-9