Beteiligte:
Terunuma, Miho;
Revilla-Sanchez, Raquel;
Quadros, Isabel M.;
Deng, Qiudong;
Deeb, Tarek Z.;
Lumb, Michael;
Sicinski, Piotr;
Haydon, Philip G.;
Pangalos, Menelas N.;
Moss, Stephen J.
Erschienen:
Society for Neuroscience, 2014
Erschienen in:
The Journal of Neuroscience, 34 (2014) 3, Seite 804-816
Sprache:
Englisch
DOI:
10.1523/jneurosci.3320-13.2013
ISSN:
0270-6474;
1529-2401
Entstehung:
Anmerkungen:
Beschreibung:
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 GABABreceptors (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.