@misc{oai:ir.soken.ac.jp:00001134, author = {高木, 佐知子 and タカギ, サチコ and TAKAGI, Sachiko}, month = {2016-02-17, 2016-02-17}, note = {It is widely accepted that swelling of brain cells is one of the physiological responses associated with neuronal activation. Such alterations lead to changes in the size of extracellular space and in ephaptic and field effect interaction, which may cause synchronized activation of neurons and local spread of epileptic discharges (Jefferys, 1995). Mass changes in volume of cortical cells in response to electrical stimulation can be detected in terms of characteristics of extracellular spaces in vivo (Dietzel et al., 1980). In the human brain, transient swelling of cortical cells due to visual stimulation was recently detected by diffusion-weight magnetic resonance imaging (DW-MRI) (Darquie et al., 2001). Mechanisms underlying activity-dependent volume changes have been pursued in several in vilro studies using brain slice preparations. However, mechanisms and candidate ion channels and/or transporters which might be involved remain unclear.
In the present study, they analyzed interactions between changes in cell volume and synaptic responses in the hippocampal slices from rodents. Swelling within the CAN area were detected as increases in transmittance of near-infrared light (IRE, 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. Stimulus-induced increases in transmittance were strongly reduced in the presence of APV and CNQX, indicating involvement of glutamate receptors. MacVicar and Hochman (1991) also reported, and they confirmed their results about this point. they also investigated that the contribution of GABAergic input to the optical signals. Application of a GABA-A receptor antagonist, bicuculline, increased the amplitude and time course of the fEPSPs but rather decreased HFS-induced optical signals. To examine the contribution of Cl- flux through GABA-A receptor channels, they measured HFS-induced signals when the extracellular solution was stepwise depleted of Cl- (72.5 mM, 41.5 mM, 10.5 mM). The peak amplitude of HFS-induced signals was decreased according to the extracellular Cl- concentration. 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 into postsynaptic neurons through GABA-A receptor channels that are activated by synaptically-released GABA is a major cause of activity-dependent swelling in the hippocampal CAN region.
Since the GAD65 KO mouse is prone to epileptic seizure as a behavioral phenotype, their results suggest that the GABAergic system is not only required for stabilizing neuronal activities but also significant for swelling in the hippocampal CAN region. It might be expected that generation, synchronization and/or propagation of epileptic activity may be caused by a variety of different mechanisms (see Hochman et al., 1995). The present results provide a new concept that can relate mechanisms of the excitability control and the volume regulation in CNS neurons, which may lead to the better understanding of epilepsy., application/pdf, 総研大甲第703号}, title = {Synaptically induced changes in cell volume in the rat hippocampal slice}, year = {} }