Postsynaptic GABABReceptor Activity Regulates Excitatory Neuronal Architecture and Spatial Memory
Year: 2014
Type: article
Abstract: Cognitive dysfunction is a common symptom in many neuropsychiatric disorders and directly correlates with poor patient outcomes. The majority of prolonged inhibitory signaling in the brain is mediated via GABAB receptors (GABABRs), but the molecular function of these receptors in cognition is ill defined. To explore the significance of GABABRs in neuronal activity and cognition, we created mice with enhanced postsynaptic GABABR signaling by mutating the serine 783 in receptor R2 subunit (S783A), which decreased GABABR degradation. Enhanced GABABR activity reduced the expression of immediate-early gene-encoded protein Arc/Arg3.1, effectors that are critical for long-lasting memory. Intriguingly, S783A mice exhibited increased numbers of excitatory synapses and surface AMPA receptors, effects that are consistent with decreased Arc/Arg3.1 expression. These deficits in Arc/Arg3.1 and neuronal morphology lead to a deficit in spatial memory consolidation. Collectively our results suggest a novel and unappreciated role for GABABR activity in determining excitatory neuronal architecture and spatial memory via their ability to regulate Arc/Arg3.1.
Source: Journal of Neuroscience
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Awards: Constructing inhibitory synapses, The role of ubiquitination in regulating GABA(A) receptor functional expression, Novel actions of neurosteroids on GABA (A) receptor trafficking, Dissecting Mechanisms of GABAB-GIRK Plasticity with Psychostimulants, Mechanisms that determine Glutamine synthetase activity in the brain
OpenAlex ID: W1969215331