Differential modulation of glutamatergic and cholinergic synapses by calcineurin in hippocampal CA1 fast-spiking interneurons.
How signaling molecules in inhibitory interneurons modulate and coordinate the integration of synaptic inputs remains largely unknown. We investigated the kinetics and modulation of glutamatergic and cholinergic synapses on CA1 fast-spiking interneurons in hippocampal slices by using whole-cell clamp recording. Spontaneous synaptic currents mediated by either AMPA-type glutamate or nicotinic acetylcholine receptors on the interneurons can be classified into fast, slow and fast-slow based on their duration and decay phase. Effects of calcineurin, calmodulin-dependent protein phosphatase, on these two groups of synapses were examined by infusing an autoinhibitory peptide of calcineurin (CaN-AIP) into the recording neurons. CaN-AIP enhanced the amplitude of glutamatergic fast-EPSCs, as well as both amplitude and frequency of cholinergic fast-EPSCs. No significant changes in slow-EPSCs were observed during the infusion of CaN-AIP. Our results indicate that signal transmission at synapses, which are mediated by either AMPA-type glutamate or nicotinic acetylcholine receptors, appears different in the kinetics. The selective influence of calcineurin on different synapses in fast-spiking interneurons may play an important role in coordinating thousands of synaptic inputs in order to set neuronal excitability at proper levels.
Wang
Jin-Hui
JH
Department of Molecular Biosciences, University of Kansas, 4023 Haworth Hall, 1200 Sunnyside, Lawrence KS 66045, USA. jinhwang@ku.edu
Zhang
Mei J
MJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D019703:Calcineurin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D014403:Tubocurarine / Q000494:pharmacology
D011950:Receptors, Cholinergic; D017470:Receptors, Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D019703:Calcineurin; D014403:Tubocurarine