Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination

Brian W. Jones; Jennifer Deem; Thomas J. Younts; Michael Weisenhaus; Christina A. Sanford; Margaret C. Slack; Jenesa Chin; Daniela Nachmanson; Alex McKennon; Pablo E. Castillo; G. Stanley McKnight

doi:10.7554/eLife.20695

Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination

Brian W. Jones, Jennifer Deem, Thomas J. Younts, Michael Weisenhaus, Christina A. Sanford, Margaret C. Slack, Jenesa Chin, Daniela Nachmanson, Alex McKennon, Pablo E. Castillo, G. Stanley McKnight

Neuroscience

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e20695
Journal	eLife
Volume	5
Issue number	DECEMBER2016
DOIs	https://doi.org/10.7554/eLife.20695
State	Published - Dec 2 2016

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.7554/eLife.20695

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title = "Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination",

abstract = "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.",

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AU - Jones, Brian W.

AU - Deem, Jennifer

AU - Younts, Thomas J.

AU - Weisenhaus, Michael

AU - Sanford, Christina A.

AU - Slack, Margaret C.

AU - Chin, Jenesa

AU - Nachmanson, Daniela

AU - McKennon, Alex

AU - Castillo, Pablo E.

AU - McKnight, G. Stanley

PY - 2016/12/2

Y1 - 2016/12/2

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AB - 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.

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Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination

Abstract

ASJC Scopus subject areas

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