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Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice
Published on: March 1, 2014
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.
Abstract:
Coiled-coil forms of Homer1, including Homer1b and c (Homer1b/c) have been shown to play a role in hippocampal learning and memory and synaptic plasticity. We have previously found that overexpression of hippocampal Homer1c is sufficient to rescue learning and memory ability in aged learning impaired rats and in Homer1 knockout (KO) mice, and to rescue group I metabotropic glutamate receptor (mGluR1/5) mediated long-term potentiation in KO mice. Here, to determine if Homer1b/c is necessary for successful learning and memory we have utilized a rAAV5 vector expressing a Homer1b/c-targeting short hairpin RNA to knock down the expression of hippocampal Homer1b/c in adult 4-6-month old male Sprague Dawley rats. We have found that reduced hippocampal Homer1b/c expression elicits significant learning deficits in contextual fear conditioning, but not in the Morris water maze or novel object recognition tasks. Furthermore, we demonstrate that reduced hippocampal Homer1b/c is sufficient to completely block mGluR1/5 mediated long-term depression in the Schaffer collateral pathway. These results support a significant role for Homer1b/c in learning and synaptic plasticity; however, the exact role of each of these two protein isoforms in learning and memory remains elusive.
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