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

Research output: Contribution to journalArticle

9 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 languageEnglish (US)
Article numbere20695
JournaleLife
Volume5
Issue numberDECEMBER2016
DOIs
StatePublished - Dec 2 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Jones, B. W., Deem, J., Younts, T. J., Weisenhaus, M., Sanford, C. A., Slack, M. C., Chin, J., Nachmanson, D., McKennon, A., Castillo, P. E., & McKnight, G. S. (2016). Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination. eLife, 5(DECEMBER2016), [e20695]. https://doi.org/10.7554/eLife.20695