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Graduate Students: Clemens, AnnKim, ChungsubPark, Yul YoungVaidya, SachinPost Doc Students: Carlson, StephanieChang, PayneDembrow, NikolaiDiaz, LaureaMathew, SeenaNarayanan, RishikeshRosenkranz, AmielRumsey, Clifton Research Summary: Research in my laboratory is primarily directed towards understanding the cellular and molecular mechanisms of synaptic integration and long-term plasticity of neurons in the medial temporal lobe. We have focused our attention on the hippocampus, subiculum, and entorhinal cortex, areas of the brain that play important roles in learning and memory. These regions are also of interest because they have a low seizure threshold and are implicated in several forms of human epilepsy. Our research uses quantitative electrophysiological, optical-imaging, and computer-modeling techniques.
We are investigating long-term synaptic potentiation and depression, forms of plasticity thought to underlie aspects of memory. This interest has led us to investigate the basic mechanisms of synaptic integration in the dendrites of the neurons in these regions. We have used fluorescence imaging techniques and dendritic patch-clamp recordings to identify the types of voltage-gated ion channels (Na+, K+, Ca+, and h channels) expressed in dendrites of hippocampal and entorhinal cortex pyramidal neurons. We have also begun to identify changes in the properties and expression levels of some of these channels accompanying synaptic potentiation and depression. These studies have suggested that plasticity of intrinsic excitability of neurons is an important component of learning and memory. Our computer modeling studies, which reconstruct the biophysical properties of these neurons based on our experimental data, complement this work. We hope that these investigations will enhance our understanding of the neuronal mechanisms of learning and memory and provide insight into the function of the hippocampus and neighboring cortex in the normal behaving animal as well as under disease states such as epilepsy.
Research Images: CA1 pryamidal neuron in hippocampus |
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Publications:| Mislocalization of h channel subunits underlies h channelopathy in temporal lobe epilepsy (2008) Neurobiol. Dis. 32, 26-36. | | The ascent of channels with memory (2008) Neuron 60, 735-738. | | Active dendrites: colorful wings of the mysterious butterflies. (2008) Trends Neurosci. 31, 309-16. | | Out of control in the dendrites. (2008) Nat. Neurosci. 11, 733-4. | | The h channel mediates location dependence and plasticity of intrinsic phase response in rat hippocampal neurons. (2008) J. Neurosci. 28, 5846-60. | | Long-term potentiation in rat hippocampal neurons is accompanied by spatially (2007) Neuron 56, 1061-75. | | Plasticity of intrinsic excitability during long-term depression is mediated through mGluR-dependent changes in I(h) in hippocampal CA1 pyramidal neurons. (2007) J. Neurosci. 27, 13926-37. | | State-dependent modulation of amygdala inputs by dopamine-induced enhancement of sodium currents in Layer V entorhinal cortex. (2007) J. Neurosci. 27, 7054-7069. | | Associative pairing enhances action potential back-propagation in radial oblique branches of CA1 pyramidal neurons. (2007) J. Physiology 580, 787-800. | | Voltage-gated ion channels in dendrites of hippocampal neurons. (2006) Pflugers Arch 453, 397-401. | | Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons. (2006) J. Neurosci 26, 12143-12151. | | Acceleration of K+ channel inactivation by the MEK inhibitor U0126. (2006) Amer. J. Physiol. 290, C165-C171. | | Voltage-dependent dopaminergic regulation of neuronal excitability through modulation of Ih in layer V entorhinal cortex (2006) J. Neuroscience 26, 3229-3244. | | Plasticity of dendritic excitability (2005) J. Neurobiol 64, 100-115. | | Activity-dependent decrease of excitability in hippocampal neurons through increases in Ih (2005) Nature Neuroscience 8, 1542-1551. | | Target-Cell Dependent Normalization of Transmitter Release at Neocortical Synapses. (2005) Science 308, 863-866. | | LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites. (2004) Nature Neuroscience 7, 126-135. | | Acquired dendritic channelopathy in temporal lobe epilepsy. (2004) Science 305, 532-535. | | Seizure-induced plasticity of h-channels in entorhinal cortical layer III neurons. (2004) Neuron 2004, 495-508. |
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