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- Title
Control of Excitation/Inhibition Balance in a Hippocampal Circuit by Calcium Sensor Protein Regulation of Presynaptic Calcium Channels.
- Authors
Nanou, Evanthia; Lee, Amy; Catterall, William A.
- Abstract
Activity-dependent regulation controls the balance of synaptic excitation to inhibition in neural circuits, and disruption of this regulation impairs learning and memory and causes many neurological disorders. The molecular mechanisms underlying short-term synaptic plasticity are incompletely understood, and their role in inhibitory synapses remains uncertain. Here we show that regulation of voltage-gated calcium (Ca2+) channel type 2.1 (Cav2.1) by neuronal Ca2+ sensor (CaS) proteins controls synaptic plasticity and excitation/ inhibition balance in a hippocampal circuit. Prevention of CaS protein regulation by introducing the IM-AA mutation in Cav2.1 channels in male and female mice impairs short-term synaptic facilitation at excitatory synapses of CA3 pyramidal neurons onto parvalbumin (PV)-expressing basket cells. In sharp contrast, the IM-AA mutation abolishes rapid synaptic depression in the inhibitory synapses of PV basket cells onto CA1 pyramidal neurons. These results show that CaS protein regulation of facilitation and inactivation of Cav2.1 channels controls the direction of short-term plasticity at these two synapses. Deletion of the CaS protein CaBPl/caldendrin also blocks rapid depression at PV-CA1 synapses, implicating its upregulation of inactivation of Cav2.1 channels in control of short-term synaptic plasticity at this inhibitory synapse. Studies of local-circuit function revealed reduced inhibition of CA1 pyramidal neurons by the disynaptic pathway from CA3 pyramidal cells via PV basket cells and greatly increased excitation/inhibition ratio of the direct excitatory input versus indirect inhibitory input from CA3 pyramidal neurons to CA1 pyramidal neurons. This striking defect in local-circuit function may contribute to the dramatic impairment of spatial learning and memory in IM-AA mice.
- Subjects
CALCIUM channels; CALMODULIN; EXCITATION (Physiology); PRESYNAPTIC receptors; NEURAL circuitry; NEUROPLASTICITY
- Publication
Journal of Neuroscience, 2018, Vol 38, Issue 18, p4430
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0022-18.2018