The objective of the proposed studies is to understand the cellular neural events that underlie sensorimotor integration in the red nucleus. Extracellular recordings from red nucleus cells in intact animals have revealed distinct sensory and motor modes of responding. Here we propose in vitro intracellular studies of these neurons to determine the cellular mechanisms that mediate the integration of sensory and motor responses. We will utilize whole-cell and perforated patch recordings from red nucleus neurons, under voltage- and current-clamp conditions. Electrical stimulation will be used to mimic the normal physiological activity in sensory and motor pathways. Most of the experiments will utilize horizontal slices through the mesencephalon of the turtle; this orientation preserves both ascending sensory and cerebellar afferents to the red nucleus. Select experiments will be repeated in brain slices from rodents to assess the generality of the findings. NMDA-, AMPA- and metabotropic-receptor mediated components of excitatory synaptic transmission, and GABAergic and glycinergic components of inhibitory and neuromodulatory transmission will be isolated neuropharmacologically. Using these intracellular data, a biophysically-based computational model of sensorimotor integration will be constructed. This computational model will be developed to the point of predicting how an individual red nucleus neuron contributes to the sensory and motor responses of the rubrocerebellar network. We anticipate that the results of these studies will be relevant to our understanding of the pathophysiology of several neurological diseases that affect the generation of limb motor commands. The spasticity of cerebrovascular disease and dystonia both involve hyperactivity of these circuits. The neuropharmacological and biophysical mechanisms we study here may suggest new therapies for these disorders of muscle tone and voluntary movement control.
| Jiang, M C; Alheid, G F; Nunzi, M G et al. (2002) Cerebellar input to magnocellular neurons in the red nucleus of the mouse: synaptic analysis in horizontal brain slices incorporating cerebello-rubral pathways. Neuroscience 110:105-21 |
