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, beta 3 integrin (ITG beta 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 beta 3-dependent processes in the brain, we examined whether the loss of ITG beta 3 affected fear-related behaviours in mice. ITG beta 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 beta 3 bilaterally in the ventral hippocampus. In hippocampal slices, the loss of ITG beta 3 activity did not compromise Hebbian forms of plasticity neither acute pharmacological disruption of ITG beta 3 ligand interactions nor genetic deletion of ITG beta 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 beta 3 activity. In contrast, acutely disrupting ITG beta 1ligand interactions or genetic deletion of ITG beta 1 selectively interfered with LTP stabilisation whereas LTD remained unaltered. These findings indicate a lack of requirement for ITG beta 3 in the two robust forms of hippocampal long-term synaptic plasticity, LTP and LTD, and suggest differential roles for ITG beta 1 and ITG beta 3 in supporting hippocampal circuit functions.