In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 34, No. 3 ( 2014-01-15), p. 804-816
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 GABA B receptors (GABA B Rs), but the molecular function of these receptors in cognition is ill defined. To explore the significance of GABA B Rs in neuronal activity and cognition, we created mice with enhanced postsynaptic GABA B R signaling by mutating the serine 783 in receptor R2 subunit (S783A), which decreased GABA B R degradation. Enhanced GABA B R 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 GABA B R activity in determining excitatory neuronal architecture and spatial memory via their ability to regulate Arc/Arg3.1.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.3320-13.2013
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2014
detail.hit.zdb_id:
1475274-8
SSG:
12
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