We focus on the functional consequences of voltage-gated potassium channel (Kv) diversity in neocortical pyramidal cells from somatosensory cortex. Specifically, we will study the functions of three types of potassium channels in neocortical pyramidal neurons: Kv1, Kv2, and Kv7 channels. The proposed studies go beyond the standard notion that potassium channels act as an intrinsic brake on excitability to studying the effects of these channels on the types of information that pyramidal cells respond to and how those inputs are transformed into trains of action potentials. Transformation of synaptic inputs into spike trains is one of the most basic and yet fundamentally important neuronal functions. Both the rate and timing of action potentials in pyramidal cells are important for cortical function, and both depend on the intensity and the spatial and temporal structure of the synaptic input to each neuron. A better understanding of the roles of particular ion channels requires tests under conditions relevant for behaving animals, yet such information is very limited at present. Neuronal dendrites are nonlinear processors, and are interposed between most synapses and the primary spike generating zone, but the effects of distributed input to dendrites on spike output remain a huge gap in our experimental understanding of single-neuron computation. We will use photo uncaging of glutamate with a digital light processing (DLP)-based system or 2-photon microscopy to rapidly and precisely control the spatio-temporal pattern and intensity of dendritic glutamate receptor activation to pyramidal cells. Using this simulated physiological input, we will investigate how the effects of Kv channels (Kv1, Kv2, Kv7) depend on the input statistics and how these Kv channels affect the encoding of overall input statistics by firing rate (""""""""rate coding""""""""), as well as the encoding of individual inpu fluctuations by precise spike timing (""""""""time coding""""""""). Time coding is important for generation of rhythmic cortical activity such as observed during attention and sensory processing.

Public Health Relevance

Knowing the detailed functions of particular K channels is essential to understanding how neurons process inputs into spike outputs and for developing more specific disease therapies. Alterations of K channel function (e.g., reduction of Kv1 or Kv7 expression) leads to pathophysiology such as epilepsy. Kv2 channels play important roles in the homeostatic suppression of neuronal hyperexcitability under pathological conditions, mediate apoptosis in PCs exposed to anoxia, and are targets of anesthetics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS044163-10
Application #
8485692
Study Section
Special Emphasis Panel (ZRG1-MDCN-B (04))
Program Officer
Silberberg, Shai D
Project Start
2002-07-01
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
10
Fiscal Year
2013
Total Cost
$326,571
Indirect Cost
$82,803
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
Pathak, Dhruba; Guan, Dongxu; Foehring, Robert C (2016) Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex. J Neurophysiol 115:2317-29
Guan, Dongxu; Armstrong, William E; Foehring, Robert C (2015) Electrophysiological properties of genetically identified subtypes of layer 5 neocortical pyramidal neurons: Ca²⁺ dependence and differential modulation by norepinephrine. J Neurophysiol 113:2014-32
Bishop, Hannah I; Guan, Dongxu; Bocksteins, Elke et al. (2015) Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons. J Neurosci 35:14922-42
Guan, Dongxu; Armstrong, William E; Foehring, Robert C (2013) Kv2 channels regulate firing rate in pyramidal neurons from rat sensorimotor cortex. J Physiol 591:4807-25
Andrade, Rodrigo; Foehring, Robert C; Tzingounis, Anastasios V (2012) The calcium-activated slow AHP: cutting through the Gordian knot. Front Cell Neurosci 6:47
Guan, Dongxu; Horton, Leslie R; Armstrong, William E et al. (2011) Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons. J Neurophysiol 105:2976-88
Guan, D; Higgs, M H; Horton, L R et al. (2011) Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons. J Neurophysiol 106:1722-33
Villalobos, Claudio; Foehring, Robert C; Lee, Jonathan C et al. (2011) Essential role for phosphatidylinositol 4,5-bisphosphate in the expression, regulation, and gating of the slow afterhyperpolarization current in the cerebral cortex. J Neurosci 31:18303-12
Foehring, Robert C; Guan, Dongxu; Toleman, Tara et al. (2011) Whole cell recording from an organotypic slice preparation of neocortex. J Vis Exp :
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

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