Matthew A. Xu-Friedman Neuronal Computation in the Auditory System Assistant Professor Ph.D. Cornell University (1997) Postdoctoral Work Harvard University (1997) Assistant Professor University at Buffalo (2004)

Address Information

Dr. Matthew A. Xu-Friedman
Department of Biological Sciences
641 Cooke Hall
State University of New York at Buffalo
Buffalo, NY 14260

(716) 645-2363 ext. 202
(716) 645-2975 (fax)

To send e-mail: mx@buffalo.edu

RESEARCH SUMMARY:

Many significant advances have been made in recent years in understanding the molecular and biophysical mechanisms underlying a wide range of channels, receptors, and modulators in the nervous system. However, much of this mechanistic work has been carried out in systems where the functional roles of individual cells are not well understood, such as cerebellum, cortex, hippocampus. Thus, very little is known how cellular properties influence neuronal function.

To address this issue, the lab uses the mammalian auditory brainstem as a model system. This system has been well studied in vivo, providing a great deal of information about the auditory pathways responsible for analyzing and localizing sounds. In addition, cells in the auditory pathway can also be studied in vitro, which allows detailed analyses of their cellular and synaptic properties. We apply in vitro methods to explain how cells in the auditory pathway can bring about the activity observed in vivo. This approach is valuable to neuroscience at large because the auditory system shares computational principles with the rest of the brain.

In addition, we are interested in synaptic structure, and how it contributes to synaptic physiology. For this we use serial electron microscopy and three-dimensional reconstructions to examine synapses in great detail, in order to explain how they behave in vitro.

Positions are available immediately for both postdocs and grad students in several projects in the lab. Please contact Dr. Xu-Friedman at mx@buffalo.edu for more information.

SELECTED PROJECTS:

• Synaptic Physiology of the Auditory Brainstem

Bushy cell synaptic currents triggered by 100 Hz activity in the auditory nerve.
Synaptic currents depress considerably by the end of the train.

We are studying the synapse made by auditory nerve fibers onto bushy cells in the anteroventral cochlear nucleus, which is called the “endbulb of Held”. In response to high frequency activation, such as is found in vivo, synaptic currents change in size (see figure above). We want to understand what processes contribute to short-term changes in synaptic strength at the endbulb. There are many processes that could be involved, including presynaptic processes such as vesicle depletion and calcium channel inactivation, as well as postsynaptic processes such as desensitization and saturation. We use voltage clamp studies in brain slices as well as calcium imaging to investigate these processes. In addition, we use dynamic clamp to determine how these processes transform information as it is passed to the bushy cell.

• Neuromodulation in the Auditory Brainstem

Bushy cell synaptic currents triggered by 100 Hz activity in the auditory nerve in the presence
of baclofen, a GABAB receptor agonist. The synapse changes from depressing to facilitating,
which could change its computational properties.

There are many neuromodulatory systems present in the cochlear nucleus, including GABAB and norepinephrine. We want to understand how modulatory systems affect different synapses within the cochlear nucleus. Neuromodulators can act presynaptically, to lower calcium influx and neurotransmitter release (see the effects of GABAB in the figure above), or postsynaptically to change resting potential or spike threshold. We want to understand how neuromodulators change the transfer of information by synapses in the cochlear nucleus. This work may provide insights into the functional roles of neuromodulators in other parts of the brain.

• Synaptic Ultrastructure

A single release site made by a cerebellar mossy fiber onto a
granule cell dendrite. Vesicles are clustered around the presynaptic
active zone, across from the postsynaptic density.

Synapses are highly specialized structures. We use electron microscopy to study how structural features of synapses may underlie their physiological properties. In addition, we are developing techniques to better understand how single release sites are organized.

SELECTED PUBLICATIONS:

• Xu-Friedman MA and Regehr WG (in press) Dynamic Clamp Analysis of the
  Effects of Convergence on Spike Timing I: Many Synaptic Inputs. J.
  Neurophysiol.

• Xu-Friedman MA and Regehr WG (in press) Dynamic Clamp Analysis of the
  Effects of Convergence on Spike Timing II: Few Synaptic Inputs. J.
  Neurophysiol.

• Xu-Friedman MA and Regehr WG (2004)
  Structural contributions to short-term synaptic plasticity.
  Physiol. Rev. 84: 69–85.

• Xu-Friedman MA and Regehr WG (2003)
  Ultrastructural contributions to desensitization at cerebellar mossy fiber to granule cell synapses.
  J Neurosci 23: 2182–2192.

• Xu-Friedman MA, Harris KM, and Regehr WG (2001)
  Three-dimensional comparison of ultrastructural characteristics at depressing and facilitating synapses onto cerebellar Purkinje cells.
  J Neurosci 21: 6666–6672.

• Xu-Friedman MA and Regehr WG (2000)
  Probing fundamental aspects of synaptic transmission with strontium.
  J. Neurosci. 20: 4414–4422.

• Xu-Friedman MA and Regehr WG (1999)
  Presynaptic strontium dynamics and synaptic transmission.
  Biophys. J. 76: 2029–2042.

• Xu-Friedman MA and Hopkins CD (1999)
  Central mechanisms of temporal analysis in the knollenorgan pathway of mormyrid electric fish.
  J. Exp. Biol. 202: 1311–1318.

• Carr CE and Friedman MA (1999)
  Evolution of time coding systems.
  Neural Comput. 11: 1–20.
  

For a complete list, contact Dr. Xu-Friedman.