Hippocampal Homer1b/c is necessary for contextual fear conditioning and group I metabotropic glutamate receptor

Kirstan Gimse1, Ryan C Gorzek2, Andrew Olin3

  • 1Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Medical Sciences Center, 1300 University Ave, Room 73 Bardeen, Madison, WI 53706, USA.

Insights

Reduced Homer1b/c in rat hippocampus impairs contextual fear learning and blocks mGluR1/5 long-term depression, suggesting a role in specific memory forms and synaptic plasticity.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Synaptic Plasticity

Background:

  • Coiled-coil Homer1 proteins (Homer1b/c) are implicated in hippocampal learning, memory, and synaptic plasticity.
  • Previous studies showed Homer1c overexpression rescues memory deficits and enhances synaptic potentiation in rats and mice.

Purpose of the Study:

  • To investigate whether Homer1b/c is essential for learning and memory.
  • To determine the necessity of Homer1b/c for synaptic plasticity.

Main Methods:

  • Used rAAV5 vectors to deliver Homer1b/c-targeting short hairpin RNA in adult male Sprague Dawley rats.
  • Assessed learning and memory using contextual fear conditioning, Morris water maze, and novel object recognition tasks.
  • Measured metabotropic glutamate receptor 1/5 (mGluR1/5) mediated long-term depression in the Schaffer collateral pathway.

Main Results:

  • Reduced hippocampal Homer1b/c expression caused significant learning deficits in contextual fear conditioning.
  • No deficits were observed in Morris water maze or novel object recognition tasks.
  • Reduced Homer1b/c completely blocked mGluR1/5 mediated long-term depression.

Conclusions:

  • Homer1b/c plays a significant role in specific forms of learning and synaptic plasticity.
  • The precise roles of Homer1b and Homer1c isoforms in learning and memory require further investigation.

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