GABAergic input contributes to activity-dependent change in cell volume in the hippocampal CA1 region

Swelling of brain cells is one of the physiological responses associated with neuronal activation. To investigate underlying mechanisms, we analyzed interactions between changes in cell volume and synaptic responses in the hippocampal slices from rodents. Swelling within the CA1 area was detected as increases in transmittance of near-infrared light (IR), and field excitatory postsynaptic potentials (fEPSPs) were recorded simultaneously. High frequency stimulation (HFS) of afferent fibers induced a transient increase in IR transmittance in both somatic and dendritic regions, which was temporally associated with fEPSPs. Stimulus-induced increases in transmittance were strongly reduced in the presence of DL-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, indicating involvement of glutamate receptors. Application of a GABA-A receptor antagonist, bicuculline, increased the amplitude and time course of the fEPSPs but rather decreased HFS-induced optical signals. When the extracellular Cl(-) was reduced to 10.5 mM, HFS induced a decrease in transmittance, which was also blocked by bicuculline. In hippocampal slices obtained from mice deficient in the 65 kDa isoform of glutamic acid decarboxylase, HFS-induced signals were significantly smaller than in the wild-type mice, although fEPSP profiles did not differ. These results suggest that Cl(-) influx through GABA-A receptors contributes to synaptically evoked swelling in the hippocampal CA1 region.