Jason Tait Sanchez, Ph.D., CCC-A

Senior Fellow
Otolaryngology-HNS
CHDD, Room CD182
University of Washington
Box 357923
Seattle, Washington 98195-7923

phone: (206) 616-4152
fax: (206) 221-5685
email: sanchj@u.washington.edu

Sound localization is a basic survival skill required of all vertebrates. The ability to locate the source of a sound is dependent on auditory information that arrives at both ears. The neurons responsible for encoding binaural information are part of a highly specialized auditory circuit found in the brainstem of birds and mammals.

Researchers, Dr. Edwin Rubel, Dr. Andres Barria and Dr. Jason Sanchez are examining how neurons in this auditory circuit develop with specific interest devoted to the excitatory neurotransmitter glutamate and its postsynaptic receptors. It is well established that events mediated by glutamate receptors are essential for various forms of activity-dependent plasticity in both developing and adult brains. How developing glutamate receptors influence the structure and function of this circuit is the focus of their research.

Nuclues laminaris (NL), a third-order auditory structure in birds, provides an ideal model system to address this issue. Structurally, NL consists of a single cell body layer with segregated symetrical dendrites (see Figure 1). Each segregated dendrite receives bilateral excitatory information from the cochlear nucleus magnocellularis on each side of the brainstem and functionally, these glutamatergic inputs provide initial cues for sound localization. However, it is unclear how glutamate receptors develop in NL and more importantly, the stuctural and functional role they play in synapse formation, refinement and dendritic arborization. The research performed by Drs. Rubel, Barria and Sanchez seeks to elucidate the developmental profile of the AMPA- and NMDA-type glutamate receptors (AMPA-Rs and NMDA-Rs, respectively) in NL during a developmental period when neuronal synapses are just forming and the onset of hearing is first emerging.

Since joining the Rubel lab, Dr. Sanchez has been characterizing the physiological signatures of AMPA- and NMDA-Rs in NL. Using whole-cell voltage clamp recordings from acute brainstem slices and pharmacological manipulations of glutamate receptors, Dr. Sanchez has shown that as early as synaptic transmission could be recorded, excitatory responses are mediated by both AMPA- and NMDA-Rs (see Figure 2). As the circuit develops, both receptors show significant changes in their response to glutamate activation (see Figure 3), suggesting maturational alterations in receptor structure and function that are associated with developmental changes.

Their research is gaining insight into the mechanisms by which physiological response properties of individual neurons contribute to the overall function of the auditory system. Understanding how synaptic mechanism influence the development of auditory properties may contribute to the improvement of appropriate therapies for individuals deprived of auditory information early in life. In addition, results from their experiments are applicable to broader questions about glutamate receptor development across the field of cellular neurophysiology, from learning and memory to diseases that affect the central nervous system.

Jason Tait Sanchez, Donald Gans, and Jeffrey J. Wenstrup. Glycinergic “Inhibition” Mediates Selective Excitatory Responses to Combinations of Sounds, The Journal of Neuroscience. 2008 Jan;28(1):80 –90 pdf

Jason Tait Sanchez, Donald Gans, and Jeffrey J. Wenstrup. Contribution of NMDA and AMPA Receptors to Temporal Patterning of Auditory Responses in the Inferior Colliculus, The Journal of Neuroscience. 2007 Feb;27(8):1954 –63 pdf

Jason Tait Sanchez, Donald Gans. Effects of Artifact Rejection and Bayesian Weighting on the Auditory Brainstem Response During Quiet and Active Behavioral Conditions, American Journal of Audiology. 2006 Dec; Vol. 15:154 –163 pdf