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 GABAA
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 GABAB 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 GABAA 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
Visitor number
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