title: β3 integrin is dispensable for conditioned fear and hebbian forms of plasticity in the hippocampus.
abstract: 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, β3 integrin (ITGβ3) 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 ITGβ3-dependent processes in the brain, we examined whether the loss of ITGβ3 affected fear-related behaviours in mice. ITGβ3-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 ITGβ3 bilaterally in the ventral hippocampus. In hippocampal slices, the loss of ITGβ3 activity did not compromise hebbian forms of plasticity--neither acute pharmacological disruption of ITGβ3 ligand interactions nor genetic deletion of ITGβ3 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 ITGβ3 activity. In contrast, acutely disrupting ITGβ1-ligand interactions or genetic deletion of ITGβ1 selectively interfered with LTP stabilisation whereas LTD remained unaltered. These findings indicate a lack of requirement for ITGβ3 in the two robust forms of hippocampal long-term synaptic plasticity, LTP and LTD, and suggest differential roles for ITGβ1 and ITGβ3 in supporting hippocampal circuit functions.
authors: Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London, UK.
authors: A B
authors: AB
authors: McGeachie
authors: A E
authors: AE
authors: Skrzypiec
authors: L A
authors: LA
authors: Cingolani
authors: M
authors: M
authors: Letellier
authors: R
authors: R
authors: Pawlak
authors: Y
authors: Y
authors: Goda
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology; D039661:Integrin beta3 / Q000235:genetics* / Q000502:physiology; D017774:Long-Term Potentiation / Q000235:genetics* / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018091:Receptors, AMPA / Q000502:physiology
chemical_list: D019012:Integrin beta1; D039661:Integrin beta3; D018091:Receptors, AMPA