NMDAR-dependent presynaptic homeostasis in adult hippocampus: Synapse growth and cross-modal inhibitory plasticity
Year: 2022
Type: article
Abstract: Homeostatic plasticity (HP) encompasses a suite of compensatory physiological processes that counteract neuronal perturbations, enabling brain resilience. Currently, we lack a complete description of the homeostatic processes that operate within the mammalian brain. Here, we demonstrate that acute, partial AMPAR-specific antagonism induces potentiation of presynaptic neurotransmitter release in adult hippocampus, a form of compensatory plasticity that is consistent with the expression of presynaptic homeostatic plasticity (PHP) documented at peripheral synapses. We show that this compensatory plasticity can be induced within minutes, requires postsynaptic NMDARs, and is expressed via correlated increases in dendritic spine volume, active zone area, and docked vesicle number. Further, simultaneous postsynaptic genetic reduction of GluA1, GluA2, and GluA3 in triple heterozygous knockouts induces potentiation of presynaptic release. Finally, induction of compensatory plasticity at excitatory synapses induces a parallel, NMDAR-dependent potentiation of inhibitory transmission, a cross-modal effect consistent with the anti-epileptic activity of AMPAR-specific antagonists used in humans.
Source: Neuron
Institutions: University of California, San Francisco, Dartmouth College
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $8,900
Awards: G1412942012, G1791655247, G1984226177, G2528705693, G4720733958, CAREER:Modulation of the Presynaptic Action Potential Shape and Impact on Synaptic Function, Neuronal Cell Biology of Kv2.1-induced Endoplasmic Reticulum/Plasma Membrane Contact sites, Homeostatic Stabilization of Neural Function in Health and Disease, The Action Potential as a Modulator of Synaptic Transmission
OpenAlex ID: W4294782829