Abstract
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.
Original language | English |
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Pages (from-to) | 1117-1129 |
Number of pages | 13 |
Journal | Cell Reports |
Volume | 19 |
Issue number | 6 |
DOIs | |
State | Published - May 9 2017 |
Bibliographical note
Publisher Copyright:© 2017 The Author(s)
Funding
We thank A. Gottschalk, J.S. Dittman, J.-L. Bessereau, H. Bringmann, and J. Rand for strains or reagents; Y.B. Qi for isolating ju836 and ju843; and Z. Wang for Cas9-mediated insertion method. We are grateful to A.D. Chisholm and our lab members for advice and comments. Some strains were provided by the Japan National BioResource Project (NBRP) and the Caenorhabditis Genetics Center (NIH P40 OD010440). This work was supported by NIH grants (R01 NS035546 to Y.J. and F32 NS081945 to S.J.C). K.Z. and A.G. are associates, and Y.J. is an Investigator, of the Howard Hughes Medical Institute.
Funders | Funder number |
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National Institutes of Health (NIH) | R01 NS035546, F32 NS081945 |
National Institutes of Health (NIH) | |
Howard Hughes Medical Institute | |
NIH Office of the Director | P40OD010440 |
NIH Office of the Director |
Keywords
- activity-dependent circuit modification
- asynchronous release
- epilepsy
- excitation-inhibition balance
- motor circuit
- presynaptic release kinetics
- seizure
- synaptic plasticity
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology