Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination

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 de...

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Bibliographic Details
Published in:eLife 2016-12, Vol.5
Main Authors: Jones, Brian W, Deem, Jennifer, Younts, Thomas J, Weisenhaus, Michael, Sanford, Christina A, Slack, Margaret C, Chin, Jenesa, Nachmanson, Daniela, McKennon, Alex, Castillo, Pablo E, McKnight, G Stanley
Format: Article
Language:English
Subjects:
A Kinase Anchor Proteins - deficiency
Ablation
Animals
CA3 Region, Hippocampal - physiology
Cerebellar Nuclei - physiology
Clonal deletion
Cyclic AMP-Dependent Protein Kinases - metabolism
Dentate gyrus
Experiments
Gene deletion
Gene Knockout Techniques
Granule cells
Hippocampal plasticity
Hippocampus
Kinases
Learning
Long-term potentiation
Medical research
Memory
Mice
Mossy Fibers, Hippocampal - physiology
Neural circuitry
Neuroscience
Physiological aspects
PKA anchoring
Presynaptic plasticity
Protein kinase A
Protein kinases
Proteins
Pyramidal cells
Rodents
Spatial Behavior
Spatial discrimination
Synaptic plasticity
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.20695