It is widely acknowledged that dopamine-containing neurons with cell bodies in the midbrain and health. The proposed work is an investigation of the properties and connections of these neurons in slices of brain tissue removed from rats and maintained in vitro. Electrical recordings will be made from neurons of the ventral tegmental area, the region of dopamine cell bodies, and the nucleus accumbens, an important limbic projection area. Intracellular whole-cell and single channel recording will be used as appropriate; currents through membrane ion channels will be isolated an measured, and excitatory and inhibitory synaptic inputs will be evoked. Particular emphasis will be accorded to investigating the actions of 5-HT and CCK since current theories of schizophrenia and anxiety hypothesize that the actions of these transmitters at 5-HT3 and CCK-B receptors may be involved. The primary objective of this project is to test nine hypotheses. Hypotheses about dopamine cells of the VTA"""""""" (1) The firing of dopamine cells is determined by the intrinsic conductance I-H; (2) Dopamine neurons receive strong GABA-A synaptic inputs from local interneurons; (3) 5-HT excites dopamine cells by inhibiting GABA release at GABA-B synapses; (4) 5-HT excites dopamine cells by activating 5-HT3 receptors; (5) CCK excites dopamine cells by acting at CCK-B receptors; and (6) CCK closes the same potassium channels that dopamine opens (at D2 receptors). Hypotheses regarding target cells of the nucleus accumbens: (7) 5-HT excites accumbens neurons by acting at 5-HT3 receptors; (8) CCK excites accumbens neurons by reducing membrane potassium conductance; (9) Dopamine acts at D3 receptors to depolarize some accumbens neurons.
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