Figure 7.

Cartoon illustrates the affect gene–environment interaction on neuronal morphology, along with alteration in function and pathophysiology of GABAergic signaling within neuronal network. In our gene–environment interaction animal model, GAD67 expression and GABA synthesis was reduced in interneurons. The decreased density of PV neurons and their enwrapping PNN might be compensated by enhanced GABAergic functions. Decrement of glycosylation of α-DG impairs the link between pre- and postsynaptic sites by connecting with the cell adhesion molecules embedded in the pre- and postsynaptic membranes. Alteration in these GABAergic neuron-associated extracellular matrix consequently may: (i) increase presynaptic input of remaining PV and non-PV (putative cholecystokinin) interneurons; (ii) affect diffusion of GABA out of the synaptic cleft to the extrasynaptic region; (iii) regulate clustering of GABA_A receptors or subunit composition; and (iv) affect function of GABA transporter (GAT) responsible for the re-uptake of GABA at synapses. These changes may in turn increase spontaneous firing of inhibitory network, decrease the threshold of stimulus of evoked IPSC, regulate decay time constant and contribute to the increased amplitude of evoked inhibitory post-synaptic currents (eIPSCs). Abbreviations: CCK, cholecystokinin; INs, interneurons; PyN, pyramidal neuron; PV, parvalbumin.