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β3 integrin is dispensable for conditioned fear and hebbian forms of plasticity in the hippocampus

, : β3 integrin is dispensable for conditioned fear and hebbian forms of plasticity in the hippocampus. European Journal of Neuroscience 36(4): 2461-2469

Integrins play key roles in the developing and mature nervous system, from promoting neuronal process outgrowth to facilitating synaptic plasticity. Recently, in hippocampal pyramidal neurons, ?3 integrin (ITG?3) was shown to stabilise synaptic AMPA receptors (AMPARs) and to be required for homeostatic scaling of AMPARs elicited by chronic activity suppression. To probe the physiological function for ITG?3-dependent processes in the brain, we examined whether the loss of ITG?3 affected fear-related behaviours in mice. ITG?3-knockout (KO) mice showed normal conditioned fear responses that were similar to those of control wild-type mice. However, anxiety-like behaviour appeared substantially compromised and could be reversed to control levels by lentivirus-mediated re-expression of ITG?3 bilaterally in the ventral hippocampus. In hippocampal slices, the loss of ITG?3 activity did not compromise Hebbian forms of plasticity neither acute pharmacological disruption of ITG?3 ligand interactions nor genetic deletion of ITG?3 altered long-term potentiation (LTP) or long-term depression (LTD). Moreover, we did not detect any changes in short-term synaptic plasticity upon loss of ITG?3 activity. In contrast, acutely disrupting ITG?1 ligand interactions or genetic deletion of ITG?1 selectively interfered with LTP stabilisation whereas LTD remained unaltered. These findings indicate a lack of requirement for ITG?3 in the two robust forms of hippocampal long-term synaptic plasticity, LTP and LTD, and suggest differential roles for ITG?1 and ITG?3 in supporting hippocampal circuit functions.In rodent hippocampal pyramidal neurons, ?3 integrin regulates synaptic AMPA receptors and is required for homeostatic plasticity. Here we find that the loss of ?3 integrin activity is dispensable for conditioned fear behaviour in mice and for LTP and LTD in acute hippocampal slices, which is in contrast to the loss of ?1 integrin that compromises LTP but not LTD. Our findings highlight differential roles for ?3 and ?1 integrins in supporting hippocampal circuit functions.


PMID: 22748100

DOI: 10.1111/j.1460-9568.2012.08163.x

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