PHYSIOLOGICAL SIGNIFICANCE OF THE SPECIFIC INCREASE OF LEFT CA3 TO RIGHT CA1 SYNAPSES ON ENVIRONMENTAL ENRICHMENT

Environmental enrichment (ENR) induces experience-dependent synaptic asymmetry in the hippocampus, characterised by a 30% selective increase in left CA3-to-right CA1 projections and a decrease in postsynaptic density (PSD) area in wild-type (WT) mice (Case et al., in preparation). However, behavioural significance of this structural plasticity remains unclear. We aim to establish the functional significance of this input-side-dependent hippocampal asymmetry by examining mice lacking this asymmetry through genetic deletion of Paired immunoglobulin-like receptor B (PirB), and to test whether ENR can overcome associated behavioural deficits.
Adult male WT and PirB knockout (KO) mice underwent behavioural testing, open field, two-compartment test, object location test, object recognition test, Barnes maze, and cued fear conditioning before and after 6 weeks of ENR, with phenotypes quantified via standard analyses.
Preliminary data from constitutive PirB KO mice revealed heightened anxiety-like behaviour, evidenced by reduced time spent in open or light compartments and increased freezing during cued fear conditioning, relative to WT controls. These findings led to the use of a CA3-specific PirB KO (conditional KO), in which preliminary results indicate normalisation of the anxiety phenotypes. Ongoing work will compare constitutive and conditional PirB KO mice with their respective controls across behavioural paradigms, followed by ENR to determine whether enrichment rescues behavioural deficits and modulates hippocampal asymmetry, elucidating the relationship between hippocampal asymmetry, experience-dependent plasticity, and learning.