[P2-3-15] Action of GABA-B receptor for local network oscillation in somatosensory cortex of oral part: focusing on oral function and NMDA receptor
Keywords:GABA-B receptor、NMDA receptor、Oscillation
Inhibitory networks play various important roles for brain activities. Balance of activity between glutamatergic and GABAergic network is especially important for information processing within neural networks. Previous studies revealed that GABA-B receptors are expressed at both presynaptic terminals, postsynaptic spine and extra-synaptic membrane. An important role of GABA-B receptor is modulation of neuron activity with driving intracellular signaling pathways. Neural oscillations are rhythmic or repetitive patterns of neural activity generated by neural networks. Here we will attempt to clarify targets of GABA-B receptor activation in local network oscillation, focusing on NMDA receptor. Brain slices were made from rats, and field potential recordings were performed from somatosensory cortex of oral parts in the medium with 3 mM-caffeine. Membrane potential oscillations at the frequency of 10 Hz were elicited by intracortical electrical stimulation. We found that initial wave was non-NMDA receptor-dependent, and later oscillatory waves were NMDA receptor-dependent. After stable oscillation was induced, baclofen, GABA-B receptor agonist, was applied. After a short time, the NMDA receptor-dependent later oscillatory phase was completely disappeared, and amplitude of initial wave was attenuated. These results indicate that main target of action of postsynaptic GABA-B receptor is NMDA receptor. Attenuation of initial wave by application of baclofen suggest that role of presynaptic GABA-B receptor may be reduction of transmitter release, since initial wave is non-NMDA receptor dependent. As a comparative experiment, we investigated how activation of GABA-B receptors modulate local network activity in manipulated rats raised under multiple tooth-losses. The NMDA receptor-dependent oscillatory phase under caffeine-application was almost blocked by the manipulation, and only initial phase remained. In this case, the initial wave was both non-NMDA receptor and NMDA receptor-dependent, unlike the case of no tooth-loss. The initial wave was attenuated by application of baclofen, which is the same as the case of no tooth-loss. Thus, these results demonstrate that (1) strengthen of initial non-NMDA receptor-dependent wave requires repetitive NMDA receptor-dependent oscillation in the somatosensory cortex, (2) main role of postsynaptic GABA-B receptor is attenuation of NMDA receptor activity, and (3) role of presynaptic GABA-B receptor may be reduction of transmitter release. Additionally, the present study suggest that adequate occlusal function is required for normal development of oscillatory neural networks regarding oral sensation.