The primary objective of the proposed study is to characterize the voltage-dependent conductances of hippocampal neurons and examine their modulation by neurotransmitters and pharmacological agents. The specific objectives are (1) To examine the properties and Ca++ dependency of three voltage- dependent K+ currents in the hippocampal cells. (2) To further characterize the calcium current; to examine its selectivity, kinetic and pharmacological properties and to use this information to assess the number of different Ca channel types that may be involved in its generation. (3) To determine the site and mode of action of two neurotransmitters, acetylocholine and norepinephrine, on the Ca and K channels. These transmitters are known to be involved in modulating the epileptiform activities of cortical neurons. Experiments will be carried out on acutely dissociation cells from hippocampus of adult guinea pigs. We have develped the dissociation technique and finalized the procedure so that viable neurons can be consistently obtained. Our results show that the cells have clean membrane surfaces allowing the application of patch-clamp technique for whole-cell and single channel recordings. Our previous data have made clear the role of single hippocampal pyramidal cells in the generation of epileptiform activities. Specifically we observed that burst firing in a single pyramidal cell can initate and entrain epileptiform synchrony in the hippocampal slice. The proposed studies on excitability of hippocampal neurons and its regulation by transmitters will be relevant to our understanding of the initiation and control of epileptiform activities in the cortex.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS024682-01
Application #
3409489
Study Section
Neurology A Study Section (NEUA)
Project Start
1987-04-01
Project End
1990-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Chen, Q X; Perkins, K L; Wong, R K (1998) Zn2+ blocks the NMDA- and Ca2+ -triggered postexposure current ipe in hippocampal pyramidal cells. J Neurophysiol 79:1124-6
Chen, Q X; Perkins, K L; Choi, D W et al. (1997) Secondary activation of a cation conductance is responsible for NMDA toxicity in acutely isolated hippocampal neurons. J Neurosci 17:4032-6
Fan, S H; Wong, R K (1996) Selective expression of transient outward currents in different types of acutely isolated hippocampal interneurons. J Neurophysiol 76:3563-7
Stewart, M; Wong, R K (1995) A method allowing intracellular and extracellular single-unit recordings from brain slices in the grease-gap chamber. J Neurosci Methods 58:17-24
Celentano, J J; Wong, R K (1994) Multiphasic desensitization of the GABAA receptor in outside-out patches. Biophys J 66:1039-50
Fan, S; Stewart, M; Wong, R K (1994) Differences in voltage-dependent sodium currents exhibited by superficial and deep layer neurons of guinea pig entorhinal cortex. J Neurophysiol 71:1986-91
Stewart, M; Wong, R K (1993) Intrinsic properties and evoked responses of guinea pig subicular neurons in vitro. J Neurophysiol 70:232-45
Wong, R K; Stewart, M (1992) Different firing patterns generated in dendrites and somata of CA1 pyramidal neurones in guinea-pig hippocampus. J Physiol 457:675-87
Chen, Q X; Wong, R K (1991) Intracellular Ca2+ suppressed a transient potassium current in hippocampal neurons. J Neurosci 11:337-43
Thompson, S M; Wong, R K (1991) Development of calcium current subtypes in isolated rat hippocampal pyramidal cells. J Physiol 439:671-89

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