John Huguenard

Administrative Appointments

• Director, Neuroscience Graduate Program, Stanford University (2006 - present)
• Professional Advisory Board, Epilepsy Foundation (2003 - present)
• Chair, Neuroscience Program Admissions Committee, Stanford University (2002 - 2005)

Honors and Awards

• Research Recognition Award, American Epilepsy Society (2007)
• Javits Merit Award, NINDS/NIH (2004-2011)

Professional Education

Postdoctoral Advisees

Catherine Christian , Chris Dulla , Carolyn Lacey , Jeanne Paz

Graduate & Fellowship Program Affiliations

• Molecular and Cellular Physiology
• Neurology and Neurol Sciences
• Neurosciences

Web Site Links

• Huguenard Lab Website

Research Interests

What are the neuronal mechanisms that underlie network oscillatory synchrony in the thalamocortical system? Such oscillations are related to cognitive processes, normal sleep activities and certain forms of epilepsy. Our approach is an analysis of the cells and microcircuits that make up thalamic and cortical circuits. We also use computational approaches to build physiologically constrained network models to test and improve our understanding of the circuit. 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 phosphorylation 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...

Publications

• Neurons that fire together also conspire together: is normal sleep circuitry hijacked to generate epilepsy? Beenhakker MP, Huguenard JR. Neuron. 2009; 62 (5): 612-32
• Robust short-latency perisomatic inhibition onto neocortical pyramidal cells detected by laser-scanning photostimulation. Brill J, Huguenard JR. J Neurosci. 2009; 29 (23): 7413-23
• Absence seizures in C3H/HeJ and knockout mice caused by mutation of the AMPA receptor subunit Gria4. Beyer B, Deleuze C, Letts VA, Mahaffey CL, Boumil RM, Lew TA, Huguenard JR, Frankel WN. Hum Mol Genet. 2008; 17 (12): 1738-49
• Sequential changes in AMPA receptor targeting in the developing neocortical excitatory circuit. Brill J, Huguenard JR. J Neurosci. 2008; 28 (51): 13918-28
• Imaging of glutamate in brain slices using FRET sensors. Dulla C, Tani H, Okumoto S, Frommer WB, Reimer RJ, Huguenard JR. J Neurosci Methods. 2008; 168 (2): 306-19