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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH040416-08A1
Application #
3378586
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1987-06-01
Project End
1997-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Organized Research Units
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Munhall, Adam C; Johnson, Steven W (2006) Dopamine-mediated actions of ephedrine in the rat substantia nigra. Brain Res 1069:96-103
Johnson, Steven W; Wu, Yan-Na (2004) Multiple mechanisms underlie burst firing in rat midbrain dopamine neurons in vitro. Brain Res 1019:293-6
Komendantov, Alexander O; Komendantova, Olena G; Johnson, Steven W et al. (2004) A modeling study suggests complementary roles for GABAA and NMDA receptors and the SK channel in regulating the firing pattern in midbrain dopamine neurons. J Neurophysiol 91:346-57
Zheng, F; Johnson, S W (2003) Dual modulation of gabaergic transmission by metabotropic glutamate receptors in rat ventral tegmental area. Neuroscience 119:453-60
Paul, Kush; Keith, Dove J; Johnson, Steven W (2003) Modulation of calcium-activated potassium small conductance (SK) current in rat dopamine neurons of the ventral tegmental area. Neurosci Lett 348:180-4
Zheng, F; Johnson, S W (2003) Metabotropic glutamate and muscarinic cholinergic receptor-mediated preferential inhibition of N-methyl-D-aspartate component of transmissions in rat ventral tegmental area. Neuroscience 116:1013-20
Zheng, Fang; Grandy, David K; Johnson, Steven W (2002) Actions of orphanin FQ/nociceptin on rat ventral tegmental area neurons in vitro. Br J Pharmacol 136:1065-71
Zheng, Fang; Johnson, Steven W (2002) Group I metabotropic glutamate receptor-mediated enhancement of dopamine cell burst firing in rat ventral tegmental area in vitro. Brain Res 948:171-4
Zheng, F; Johnson, S W (2001) Glycine receptor-mediated inhibition of dopamine and non-dopamine neurons of the rat ventral tegmental area in vitro. Brain Res 919:313-7
Shen, K Z; Johnson, S W (2001) Potentiation of GABA(A) receptor agonists by GABA uptake inhibitors in the rat ventral midbrain. Eur J Pharmacol 428:1-7

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