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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MDCN-B (04))
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Silberberg, Shai D
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University of Tennessee Health Science Center
Anatomy/Cell Biology
Schools of Medicine
United States
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Wang, Lie; Chandaka, Giri Kumar; Foehring, Robert C et al. (2018) Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy. J Neurophysiol 119:1745-1752
Baker, Arielle; Kalmbach, Brian; Morishima, Mieko et al. (2018) Specialized Subpopulations of Deep-Layer Pyramidal Neurons in the Neocortex: Bridging Cellular Properties to Functional Consequences. J Neurosci 38:5441-5455
Guan, Dongxu; Pathak, Dhruba; Foehring, Robert C (2018) Functional roles of Kv1-mediated currents in genetically identified subtypes of pyramidal neurons in layer 5 of mouse somatosensory cortex. J Neurophysiol 120:394-408
Kirchner, Matthew K; Foehring, Robert C; Callaway, Joseph et al. (2018) Specificity in the interaction of high-voltage-activated Ca2+ channel types with Ca2+-dependent afterhyperpolarizations in magnocellular supraoptic neurons. J Neurophysiol 120:1728-1739
Kirchner, Matthew K; Foehring, Robert C; Wang, Lie et al. (2017) Phosphatidylinositol 4,5-bisphosphate (PIP2 ) modulates afterhyperpolarizations in oxytocin neurons of the supraoptic nucleus. J Physiol 595:4927-4946
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
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 (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
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

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