The long-term objective of this research is to elucidate the structure and function of local circuits within cortical regions of the vertebrate central nervous system. These circuits are extremely difficult to analyze in most cortical systems. The vertebrate olfactory bulb has been a valuable simple model for this purpose, and we will continue to use it in the proposed research. The methods will be based primarily on intracellular analysis of single neurons in an in vitro preparation of the turtle olfactory bulb. A major focus will be on dendro-dendritic synaptic interactions of mitral cells, elicited by antidromic and orthodromic activation, and intracellular current injection. Very slow potentials, lasting up to one minute or more, will be analyzed using different stimulus repetition rates. Self-inhibition, miniature synaptic potentials, and excitable properties of mitral cell dendrites will be analyzed, together with impulse firing frequences elicited by current injection. Neuromodulator actions of enkephalin, dopamine and acetylcholine will be tested. Fluxes of K+ during the synaptic potentials will be studied using ion-selective electrodes. Models of these neuronal properties will be constructed on an electrical network analysis program to aid in the analysis. Patch clamp recordings will be made from neurons dissociated from the in vitro bulb surface. Parallel studies will characterize the properties of olfactory receptor cells. Similar studies will be carried out on the smaller output neurons (tufted cells), and the intrinsic neurons (granule and periglomerular short-axon cells). New methods for microstimulation of intrinsic bulbar pathways will be developed. A unique study will correlate single-neuron membrane properties with single-neuron changes in energy metabolism, as revealed by high-resolution localization of 2-deoxyglucose using methods of quick-freeze and freeze-substitution. These results should give a much clearer understanding of neuronal structure-function relations within different cortical regions of the nervous system. The results should provide insight into normal functions of microcircuits within the central nervous system, and abnormal functions related to epilepsy, schizophrenia, and Alzheimer's dementia; they should also provide crucial information relating to current controversies about the neuronal basis of energy metabolism underlying brain imaging techniques.
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