The Huguenard Lab

Studies of Thalamocortical Synchrony and Epilepsy

John R. Huguenard, Ph.D.

    We are interested in the neuronal mechanisms that underlie synchronous oscillatory activity in the thalamus, cortex and the massively interconnected thalamocortical system. Such oscillations are related to cognitive processes, normal sleep activities and certain forms of epilepsy.
    Our approach is an analysis of the discrete components that make up thalamic and cortical circuits, and reconstitution of components into both in vitro biological and in silico computational networks. Accordingly, we have been able to identify genes whose products, mainly ion channels, play key roles in the regulation of thalamocortical network responses.

 

Currently, projects focus on:

• Development of excitatory connections in neocortex, with an emphasis on AMPA receptor alterations in the early postnatal period
• Molecular pharmacology of inhibitory GABA_A receptors in the thalamus, and the role of receptor binding unbinding and desensitization in regulating inhibitory function
• Analysis of progression and destabilization of widespread thalamic network activity using large microelectrode arrays
• The roles of neuropeptides, especially NPY, SST, and VIP in regulating thalamic and cortical function
• Reorganization of neocortical connectivity following injury
• Roles of specific GABA_B receptors in regulating pre- and postsynaptic function.

The laboratory uses experimental techniques ranging from biophysical studies of single ion channels to in vivo recording to purely theoretical studies of network synchrony. Our toolbox includes:

• Use of mutant mouse models for analysis of gene function in circuit behavior. For example, knockout and knockin mice have been used to identify the specific GABA_A receptor isoforms that are critical for the therapeutic actions of benzodiazepines in thalamus.
• Patch clamp recording methods for single channels and whole cell currents, with both isolated neurons and those in situ in brain slices
• Multi-unit, multi-site extracellular recording techniques
• Immunohistochemical techniques for cell identification and protein localization
• Molecular & genetic approaches for in situ hybridization of specific transcripts
• Microscopic techniques for computerized neuronal reconstruction (Neurolucida)
• Laser uncaging of photo-labile glutamate derivatives for circuit analysis
• Imaging of network activity via FRET glutamate nanosensors
• Single cell intracellular perfusion for modification of e.g., phosphorylation state
• Paired intracellular recordings for analysis of single-axon synaptic connection
• Fluorometric detection of calcium indicator dyes in cells and circuits
• Local perfusion within slice micro-regions for pharmacological analysis
• Computer-based modeling of single cell and circuit behaviors

 

Awards and News    People   Publications  Misc lab photos   Some completed projects    Methods programs (synaptic current detector, etc.)   Lab documents and photo albums  Metatape analysis program Epilepsy Training Program  Lab Meeting The Neurology/Neuroscience Softball Team ( Myoclonic Jerks)  Links   Brian Halibisky's tutorial on Cluster Analysis

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Comments or Questions:

John.Huguenard@stanford.edu

Department of Neurology and Neurological Sciences
Room M030 Alway Building
Stanford University School of Medicine
Stanford, CA 94305-5122
Phone: 650-723-5522
Fax: 650-723-1080