A MODEL OF ACTIVITY-DEPENDENT ANATOMICAL INHIBITORY PLASTICITY APPLIED TO THE MAMMALIAN AUDITORY-SYSTEM

We construct a model of activity-dependent, anatomical inhibitory plas ticity. We apply the model to the mammalian auditory system. Specifica lly, we model the activity-dependent topographic refinement of inhibit ory projections in the auditory brain stem, and we construct an anatom ically abstract model of binaural band formation in the primary audito ry cortex involving the segregation of different populations of inhibi tory and excitatory afferents. Issues raised and predictions made incl ude the nature of interactions between excitatory and inhibitory affer ents innervating the same population of target cells, and the possibil ity that pharmacological manipulations of the developing primary audit ory cortex might induce a shift in the periodicity of binaural bands. Any model of inhibitory plasticity must confront the issue of postulat ing mechanisms underlying such plasticity. In order to attempt to unde rstand, at least theoretically, what the mechanisms underlying inhibit ory plasticity might be, we propose the existence of a new class of ne urotrophic factors that promote neurite outgrowth from and mediate com petitive interactions between inhibitory afferents. We suppose that su ch factors are up-regulated by hyperpolarisation and down-regulated by depolarisation. Furthermore, we suppose that their activity-dependent release from target cells depends on Cl- influx. Such factors are the refore assumed to be the physiological inverse of such factors as nerv e growth factor and brain-derived neurotrophic factor, which are up-re gulated by depolarisation and down-regulated by hyperpolarisation, wit h their activity-dependent release depending on Na+, and not Ca2+, inf lux.