We request funds to continue our in vitro studies of the electrophysiological properties of single large neurons in layer V of the cat pericruciate neocortex. In the last decade and particularly in the last five years major advances have been made in our understanding of the ionic mechanisms of the responses of neurons in the mammalian central nervous system (CNS). Our long-term objective is to understand the mechanisms whereby neurons of the mammalian CNS transduce synaptic inputs into spike trains for transmission of information on to the next cellular relay. In these experiments we will use the slice preparation and either the single or double microelectrode voltage clamp to measure ionic currents. In addition to studying voltage- and time-dependent currents, we will examine the effects of putative neurotransmitters such as acetylcholine, excitatory amino acids and neuropeptides that, based on the studies of others, cause a transient change (modulation) in the ionic currents and therefore the transduction properties of these neurons. These studies have health and biologic significance. The large neurons of layer V of sensorimotor cortex are the major output to lower centers and the spinal cord. If we are to understand major neurological problems such as epilepsy and degenerative diseases of cortex such as amyotrophic lateral sclerosis and Alzheimer's disease we must first know the normal neurobiologic properties of neocortical neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016792-06
Application #
3397124
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1982-04-01
Project End
1988-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Oakley, J C; Schwindt, P C; Crill, W E (2001) Dendritic calcium spikes in layer 5 pyramidal neurons amplify and limit transmission of ligand-gated dendritic current to soma. J Neurophysiol 86:514-27
Oakley, J C; Schwindt, P C; Crill, W E (2001) Initiation and propagation of regenerative Ca(2+)-dependent potentials in dendrites of layer 5 pyramidal neurons. J Neurophysiol 86:503-13
Schwindt, P; Crill, W (1999) Mechanisms underlying burst and regular spiking evoked by dendritic depolarization in layer 5 cortical pyramidal neurons. J Neurophysiol 81:1341-54
Crill, W E; Schwindt, P C (1999) Membrane properties and epilepsy. Adv Neurol 79:493-8
Lampl, I; Schwindt, P; Crill, W (1998) Reduction of cortical pyramidal neuron excitability by the action of phenytoin on persistent Na+ current. J Pharmacol Exp Ther 284:228-37
Schwindt, P C; Crill, W E (1998) Synaptically evoked dendritic action potentials in rat neocortical pyramidal neurons. J Neurophysiol 79:2432-46
Schwindt, P C; Crill, W E (1997) Modification of current transmitted from apical dendrite to soma by blockade of voltage- and Ca2+-dependent conductances in rat neocortical pyramidal neurons. J Neurophysiol 78:187-98
Mittmann, T; Linton, S M; Schwindt, P et al. (1997) Evidence for persistent Na+ current in apical dendrites of rat neocortical neurons from imaging of Na+-sensitive dye. J Neurophysiol 78:1188-92
Schwindt, P; O'Brien, J A; Crill, W (1997) Quantitative analysis of firing properties of pyramidal neurons from layer 5 of rat sensorimotor cortex. J Neurophysiol 77:2484-98
Widener, G L; Cheney, P D (1997) Effects on muscle activity from microstimuli applied to somatosensory and motor cortex during voluntary movement in the monkey. J Neurophysiol 77:2446-65

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