Howard T. Chang, MD,University of Tennessee 1996 PhD, Michigan State University 1981 - US grants

The overall objective of this project is to obtain a better understanding, at the cellular level, of the anatomical and physiological basis of functional interactions between motivation-emotional centers of the brain and motor-behavioral centers of the brain. The proposed studies will focus on the functional interactions between the limbic system and the basal ganglia in the rat brain. Specifically, the nature of basal ganglia neuron circuits involved in processing limbic afferents will be investigated. Since the ventral strio-pallidal system of the basal ganglia receive the bulk of afferent inputs from the limbic system, studies proposed here will determine the synaptic organization of neurons in the ventral strio-pallidal system, and their functional interaction with limbic afferents. The planned studies will use the technique of intracellular recording IN VIVO to analyze physiological properties of neurons in the ventral strio-pallidal system. The nature of afferent inputs from the limbic system will be studied by stimulation of respective limbic nuclei (e.g., amygdala). In addition, we will utilize the technique of intracellular horseradish peroxidase labeling to examine the morphology and the synaptic relationships of the physiologicaly identified neurons, at both the light and the electron microscopic levels. We will also perform studies involving histochemistry and/or immunocytochemistry on tissue containing intracelularly labeled neurons in order to determine the neurochemical properties of the labeled neurons and their synaptic partners. The multidisciplinary studies proposed in this project are unique to the ventral forebrain. The data will enhance our understanding of functional and anatomical properties of neuron circuits in the ventral strio-pallidal system, and the nature of their interactions with the limbic system. The results will be useful in refining present models of basal ganglia functions, and will be necessary for forumulation of both preventive and therapeutic treatments of basal ganglia disorders such as Huntington's Disease and Parkinsonism.

The overall objective is to obtain a better understanding of the regulation of the cholinergic innervation of the cerebral cortex. We propose experiments which are expected to provide answers to questions concerning the functional and anatomical organization of the cholinergic neurons in the Nucleus Basalis of Meynert and their relationships with the ventral strio-pallidal system. The planned studies will use the technique of intracellular recording IN VIVO to study the physiological properties of Nucleus Basalis neurons. The nature of afferent inputs will be studied by stimulation of respective areas. Moreover, we will utilize the technique of intracellular horseradish peroxidase labeling to examine the morphology and the synaptic relationships of the physiologically identified Nucleus Basalis neurons. We will also perform experiments involving histochemistry and/or immunocytochemistry on tissue containing intracellularly labeled neurons in order to determine the neurochemical properties of the labeled neurons and their synaptic partners. The multidisciplinary studies proposed in this project are unique to the ventral forebrain. The data will enhance our understanding of both the intrinsic functional organization of neurons in the Nucleus Basalis, and the nature of afferent regulations of cholinergic neurons which innervate the cortex. This information will be useful in the formulation of both preventive and therapeutic treatments of Alzheimer's Disease.

The long term objective of this project is to obtain a better understanding of the regulation of cholinergic innervation of the cerebral cortex. Since most of the cholinergic input to the neocortex arises from the Nucleus Basalis of Meynert, the proposed studies in this project ar focused on the elucidation of the anatomical and physiological properties of neurons in the rat substantia innominata - ventral pallidum (SI-VP) complex, within which are located the cortex-projecting neurons homologous to the cholinergic neurons of the primate Nucleus Basalis of Meynert. The planned studies will use the technique of intracellular recording In Vivo to analyze physiological properties of neurons in the rat SI-VP complex. The nature of afferent inputs will be studied by stimulation of respective areas. Moreover, we will utilize the technique of intracellular labeling with biocytin to examine the morphology and the synaptic relationships of the physiologically identified neurons. Since most neurons within the SI-VP complex are not cholinergic neurons, we will employ double-labeling methods to identify the transmitter contained within the intracellularly labeled neurons, and to determine their synaptic relationships with other immunocytochemically identified neuronal elements. We will carry out other additional single and double-labeling immunocytochemical studies at both light microscopic and electron microscopic levels in order to determine the distribution and the synaptic relationships of various non-cholinergic neurons in rat SI-VP complex. These information will be useful in the revising our current functional model of the Nucleus Basalis of Meynert, and may contribute to formulation of both preventive and therapeutic treatments of Alzheimer's Disease.