There is compelling evidence for the involvement of the hippocampus in the processing and storage of information by the nervous system. Furthermore, these functions must be accomplished by the basic units of the hippocampus, the neurons and their various interconnections. Individual pyramidal neurons in the hippocampus are complex units of integration that dynamically change with their environment. The long-term objective is to understand how a pyramidal neuron integrates and stores the information it receives from the tens of thousands of excitatory and inhibitory synaptic inputs impinging on its dendrites. Understanding how a pyramidal neuron performs these functions will only come from knowledge about the biophysical properties of these neurons and how they respond to synaptic input. This project focuses on the properties and function of voltage-gated ion channels in pyramidal neuron dendrites. Previously, single Na+ channels and at least three types of Ca2+ channels in dendrites of CA1 neurons were investigated. Here, it is proposed to continue the investigation of dendritic ion channels by focusing on certain unknown properties of these channels, on exploring further the properties of newly discovered channels, and on the neurotransmitter modulation of these channels. The experiments will utilize hippocampal brain slices, patch-clamp electrophysiology, computer modeling, and two recent techniques: high-speed fluorescence imaging and dendritic patch clamping under visual control. Neuronal dendrites are altered in specific ways in epilepsy, Alzheimer's disease, and schizophrenia. It is expected that the results of the study will provide important information about the functional significance of these disease-related changes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH048432-09
Application #
2890480
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Program Officer
Glanzman, Dennis L
Project Start
1991-09-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Neurosciences
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Kim, C S; Brager, D H; Johnston, D (2018) Perisomatic changes in h-channels regulate depressive behaviors following chronic unpredictable stress. Mol Psychiatry 23:892-903
Heuermann, Robert J; Jaramillo, Thomas C; Ying, Shui-Wang et al. (2016) Reduction of thalamic and cortical Ih by deletion of TRIP8b produces a mouse model of human absence epilepsy. Neurobiol Dis 85:81-92
Ashhad, Sufyan; Johnston, Daniel; Narayanan, Rishikesh (2015) Activation of InsP? receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons. J Neurophysiol 113:2002-13
Dembrow, Nikolai C; Zemelman, Boris V; Johnston, Daniel (2015) Temporal dynamics of L5 dendrites in medial prefrontal cortex regulate integration versus coincidence detection of afferent inputs. J Neurosci 35:4501-14
Edwards, John; Daniel, Eric; Kinney, Justin et al. (2014) VolRoverN: enhancing surface and volumetric reconstruction for realistic dynamical simulation of cellular and subcellular function. Neuroinformatics 12:277-89
Clemens, Ann M; Johnston, Daniel (2014) Age- and location-dependent differences in store depletion-induced h-channel plasticity in hippocampal pyramidal neurons. J Neurophysiol 111:1369-82
Vaidya, Sachin P; Johnston, Daniel (2013) Temporal synchrony and gamma-to-theta power conversion in the dendrites of CA1 pyramidal neurons. Nat Neurosci 16:1812-20
Brager, Darrin H; Lewis, Alan S; Chetkovich, Dane M et al. (2013) Short- and long-term plasticity in CA1 neurons from mice lacking h-channel auxiliary subunit TRIP8b. J Neurophysiol 110:2350-7
Routh, Brandy N; Johnston, Daniel; Brager, Darrin H (2013) Loss of functional A-type potassium channels in the dendrites of CA1 pyramidal neurons from a mouse model of fragile X syndrome. J Neurosci 33:19442-50
Dougherty, Kelly A; Nicholson, Daniel A; Diaz, Laurea et al. (2013) Differential expression of HCN subunits alters voltage-dependent gating of h-channels in CA1 pyramidal neurons from dorsal and ventral hippocampus. J Neurophysiol 109:1940-53

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