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

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, b3 integrin (ITGb3) 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 ITGb3-dependent processes in the brain, we examined whether the loss of ITGb3 affected fear-related behaviours in mice. ITGb3-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 ITGb3 bilaterally in the ventral hippocampus. In hippocampal slices, the loss of ITGb3 activity did not compromise Hebbian forms of plasticity – neither acute pharmacological disruption of ITGb3 ligand interactions nor genetic deletion of ITGb3 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 ITGb3 activity. In contrast, acutely disrupting ITGb1–ligand interactions or genetic deletion of ITGb1 selectively interfered with LTP stabilisation whereas LTD remained unaltered. These findings indicate a lack of requirement for ITGb3 in the two robust forms of hippocampal long-term synaptic plasticity, LTP and LTD, and suggest differential roles for ITGb1 and ITGb3in supporting hippocampal circuit functions.