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1.
Elife ; 52016 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-27911261

RESUMO

Protein Kinase A (PKA) mediates synaptic plasticity and is widely implicated in learning and memory. The hippocampal dentate gyrus (DG) is thought to be responsible for processing and encoding distinct contextual associations in response to highly similar inputs. The mossy fiber (MF) axons of the dentate granule cells convey strong excitatory drive to CA3 pyramidal neurons and express presynaptic, PKA-dependent forms of plasticity. Here, we demonstrate an essential role for the PKA anchoring protein, AKAP7, in mouse MF axons and terminals. Genetic ablation of AKAP7 specifically from dentate granule cells results in disruption of MF-CA3 LTP directly initiated by cAMP, and the AKAP7 mutant mice are selectively deficient in pattern separation behaviors. Our results suggest that the AKAP7/PKA complex in the MF projections plays an essential role in synaptic plasticity and contextual memory formation.


Assuntos
Proteínas de Ancoragem à Quinase A/deficiência , Região CA3 Hipocampal/fisiologia , Núcleos Cerebelares/fisiologia , Técnicas de Inativação de Genes , Fibras Musgosas Hipocampais/fisiologia , Comportamento Espacial , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Camundongos
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