Serotonin has long been recognized as a neurotransmitter in the mammalian central nervous system, and as such has been implicated in a variety of behavioral functions. While substantial knowledge has accumulated regarding the biochemical processes involved in its synthesis, release and reuptake, its localization in the central nervous system and its binding sites, relatively little is still known about its postsynaptic actions, their pharmacology and their ionic and molecular bases. This application proposes, therefore, to examine the effects of serotonin in two regions of the mammalian brain; the hippocampus and prefrontal cortex. Based upon binding studies it has been proposed that these two areas are particularly enriched in the two best known subtypes of serotonin binding sites and therefore are potentially ideal locations to study serotonergic receptors and their mechanisms of actions. Four issues will be addressed in these areas: 1) the electrophysiological actions of serotonin; 2) the pharmacology of the serotonin receptor involved in these actions; 3) the final effector mechanisms responsible for the observed effects; and 4) the transmembrane signalling mechanism used by these receptors. These studies will be conducted using intracellular recordings in in vitro rat brain slices and will involve the use of current and voltage clamp methods. This study should elucidate some of the mechanisms involved in the actions of serotonin in the central nervous system and therefore should ccontribute significantly to our present understanding of serotonergic functions in the central nervous system as well as its associated pathological states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024205-07
Application #
2265103
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-12-01
Project End
1994-11-30
Budget Start
1992-12-01
Budget End
1994-11-30
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Isaacson, J S; Nicoll, R A (1993) The uptake inhibitor L-trans-PDC enhances responses to glutamate but fails to alter the kinetics of excitatory synaptic currents in the hippocampus. J Neurophysiol 70:2187-91
Isaacson, J S; Solis, J M; Nicoll, R A (1993) Local and diffuse synaptic actions of GABA in the hippocampus. Neuron 10:165-75
Solis, J M; Nicoll, R A (1992) Postsynaptic action of endogenous GABA released by nipecotic acid in the hippocampus. Neurosci Lett 147:16-20
Solis, J M; Nicoll, R A (1992) Pharmacological characterization of GABAB-mediated responses in the CA1 region of the rat hippocampal slice. J Neurosci 12:3466-72
Sah, P; Nicoll, R A (1991) Mechanisms underlying potentiation of synaptic transmission in rat anterior cingulate cortex in vitro. J Physiol 433:615-30
Lancaster, B; Nicoll, R A; Perkel, D J (1991) Calcium activates two types of potassium channels in rat hippocampal neurons in culture. J Neurosci 11:23-30
Nicoll, R A; Malenka, R C; Kauer, J A (1990) Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system. Physiol Rev 70:513-65
Hestrin, S; Nicoll, R A; Perkel, D J et al. (1990) Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices. J Physiol 422:203-25
Hestrin, S; Sah, P; Nicoll, R A (1990) Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices. Neuron 5:247-53
Perkel, D J; Hestrin, S; Sah, P et al. (1990) Excitatory synaptic currents in Purkinje cells. Proc Biol Sci 241:116-21

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