Neocortical pyramidal neurons are a model system for study of the mechanisms and significance of transduction of synaptic inputs into spike trains. Several aspects of this transduction process are Ca2+-dependent, including regulation of the interspike interval (ISI), spike frequency adaptation (SFA), spike timing and afterhyperpolarizations (AHPs). Pyramidal cells express at least five different high voltage-activated Ca2+ channels. We hypothesize that Ca2+ entry has different consequences for these cells, depending upon which calcium channel subtypes are involved. An example of such partitioning of function is generation of AHPs: N-, P-, and Q-type channels couple to the sAHP and P-type to the mAHP. Two critical negative feedback systems controlling Ca2+ entry are Ca2+-dependent inactivation of Ca2+ channels and activation of Ca2+-dependent K+ channels. Both processes are potential regulators of pyramidal cell firing behavior. We will use whole cell electrical recordings and fura-2 Ca2+ imaging techniques on mature pyramidal cells in both acutely dissociated and brain slice preparations to test hypotheses about the roles of Ca2+-dependent inactivation and the relationships between action potentials, [Ca2+]i, and AHP currents (due to Ca2+-dependent K+ channels).
Aim 1 addresses the importance of Ca2+-dependent inactivation of Ca2+ channel subtypes and which channel subtypes are involved.
Aim 2 characterizes the relationships between firing frequency, IAHP, and [Ca2+]i in mature pyramidal cells. These data are important for understanding how pyramidal cells integrate synaptic inputs, and how this process is influenced by transmitters and ontogeny. (In neocortical pyramidal neurons, both Ca2+ and Ca2+-dep K+ channels are developmentally regulated and are targets for several neuromodulators). Neuronal activity and its modulation regulate cortical function and the use-dependent plasticity of cortical connections. These studies will contribute to understanding essential cortical functions such as attention, learning, and memory as well as basic mechanisms of diseases such as epilepsy, anxiety and depression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS033579-08
Application #
6639471
Study Section
Special Emphasis Panel (ZRG1-MDCN-4 (01))
Program Officer
Stewart, Randall
Project Start
1995-01-01
Project End
2006-03-31
Budget Start
2003-04-01
Budget End
2006-03-31
Support Year
8
Fiscal Year
2003
Total Cost
$177,500
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Goldberg, Joshua A; Teagarden, Mark A; Foehring, Robert C et al. (2009) Nonequilibrium calcium dynamics regulate the autonomous firing pattern of rat striatal cholinergic interneurons. J Neurosci 29:8396-407
Foehring, R C; Zhang, X F; Lee, J C F et al. (2009) Endogenous calcium buffering capacity of substantia nigral dopamine neurons. J Neurophysiol 102:2326-33
Lee, J C F; Callaway, J C; Foehring, R C (2005) Effects of temperature on calcium transients and Ca2+-dependent afterhyperpolarizations in neocortical pyramidal neurons. J Neurophysiol 93:2012-20
Timmons, S D; Geisert, E; Stewart, A E et al. (2004) alpha2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons. Brain Res 1014:184-96
Foehring, R C; van Brederode, J F M; Kinney, G A et al. (2002) Serotonergic modulation of supragranular neurons in rat sensorimotor cortex. J Neurosci 22:8238-50
Stewart, A E; Foehring, R C (2001) Effects of spike parameters and neuromodulators on action potential waveform-induced calcium entry into pyramidal neurons. J Neurophysiol 85:1412-23
van Brederode, J F; Foehring, R C; Spain, W J (2000) Morphological and electrophysiological properties of atypically oriented layer 2 pyramidal cells of the juvenile rat neocortex. Neuroscience 101:851-61
Foehring, R C; Mermelstein, P G; Song, W J et al. (2000) Unique properties of R-type calcium currents in neocortical and neostriatal neurons. J Neurophysiol 84:2225-36
Stewart, A; Foehring, R C (2000) Calcium currents in retrogradely labeled pyramidal cells from rat sensorimotor cortex. J Neurophysiol 83:2349-54
Stewart, A E; Yan, Z; Surmeier, D J et al. (1999) Muscarine modulates Ca2+ channel currents in rat sensorimotor pyramidal cells via two distinct pathways. J Neurophysiol 81:72-84

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