title: Regulation of ambient GABA levels by neuron-glia signaling for reliable perception of multisensory events.
abstract: Activities of sensory-specific cortices are known to be suppressed when presented with a different sensory modality stimulus. This is referred to as cross-modal inhibition, for which the conventional synaptic mechanism is unlikely to work. Interestingly, the cross-modal inhibition could be eliminated when presented with multisensory stimuli arising from the same event. To elucidate the underlying neuronal mechanism of cross-modal inhibition and understand its significance for multisensory information processing, we simulated a neural network model. Principal cell to and GABAergic interneuron to glial cell projections were assumed between and within lower-order unimodal networks (X and Y), respectively. Cross-modality stimulation of Y network activated its principal cells, which then depolarized glial cells of X network. This let transporters on the glial cells export GABA molecules into the extracellular space and increased a level of ambient (extrasynaptic) GABA. The ambient GABA molecules were accepted by extrasynaptic GABA(a) receptors and tonically inhibited principal cells of the X network. Cross-modal inhibition took place in a nonsynaptic manner. Identical modality stimulation of X network activated its principal cells, which then activated interneurons and hyperpolarized glial cells of the X network. This let their transporters import (remove) GABA molecules from the extracellular space and reduced tonic inhibitory current in principal cells, thereby improving their gain function. Top-down signals from a higher-order multimodal network (M) contributed to elimination of the cross-modal inhibition when presented with multisensory stimuli that arose from the same event. Tuning into the multisensory event deteriorated if the cross-modal inhibitory mechanism did not work. We suggest that neuron-glia signaling may regulate local ambient GABA levels in order to coordinate cross-modal inhibition and improve neuronal gain function, thereby achieving reliable perception of multisensory events.
authors.affiliation: Department of Intelligent Systems Engineering, Ibaraki University, Hitachi, Ibaraki, 316-8511, Japan. hoshino@mx.ibaraki.ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Hoshino
mesh_terms: D002450:Cell Communication / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D016571:Neural Networks, Computer; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010465:Perception / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid