Matthew J. Fischl
PhD Candidate
Lehigh University

Department of Biological Sciences
111 Research Drive, B217
Bethlehem, PA 18015

E-mail

Ph.D. Advisor:
R. Michael Burger, Ph.D.

Research

The diversity of neurons and their circuits is mirrored by the vast array of behaviors organisms exhibit. I am interested in the specializations in morphology, cellular physiology, synaptic transmission, plasticity and development of neurons and how these characteristics relate to the functional tasks their circuits perform. My research focuses on how inhibitory input modulates the activity in an auditory brainstem circuit that processes sound localization cues. Low frequency sounds are localized by comparing the arrival time of the sound at each ear. This cue is called interaural time disparity (ITD) and is processed in the brainstem by neurons that integrate binaural inputs. Because this cue is so small (sub-millisecond), the circuit that performs this computation is specialized to maintain precise timing information. Inhibition is an important feature of this circuit, which helps to maintain accurate sound localization ability. I use electrophysiological techniques to address questions regarding the cellular and synaptic physiology of neurons in the sound localization circuitry.

 

Fluorescently-labeled MSO neurons

MSO neurons labeled with biocytin during recording

GABA_B receptor modulation of input to coincidence detecting neurons in the mammalian brainstem

Neurons in the medial superior olive in the mammalian brainstem integrate bilateral excitatory and inhibitory inputs during the computation of sound localization. The magnitude of these inputs varies with the intensity of the sound stimuli and therefore MSO neurons are likely to receive a large range of input magnitudes. Without modulation these differences in input magnitude could lead to ambiguities in the timing of the output of MSO neurons to higher order auditory nuclei, resulting in reduced localization accuracy. Since it has been shown that MSO neurons maintain their ITD sensitivity over a broad range of stimulus intensities in vivo, it is likely that there are compensatory mechanisms that help maintain the circuit in an operational range.

Using in vitro slice physiology, my work has shown that the GABA_B receptor modulates the inputs to MSO neurons. GABA_B receptor activation reduces the amplitude of both excitatory and inhibitory inputs and reduces the amount of synaptic depression that occurs during stimulation at frequencies in the audible range. Functional tests in vitro show that activation of GABA_B receptors increases the selectivity of neurons to simulated ITDs.
(Fischl et al., 2012, J Phys)

Biocytin labeled SON neuron with extensive branching

Rhodamine injection labeling inputs to the nucleus magnocellularis

Glycinergic transmission in the avian auditory brainstem

For the last several decades research regarding inhibitory input in the avian sound localization circuitry has centered on the effects of GABAergic input. Recent findings regarding the presence of glycinergic transmission has lead to the reconsideration of inhibitory activity in the avian brainstem. The superior olivary nucleus is the main source of inhibitory inputs to brainstem nuclei involved in the sound localization circuit.

My work in the avian brainstem focuses on the synaptic physiology of the superior olivary nucleus and its targets. Both in vivo and in vitro studies have shown that glycinergic transmission occurs at SON synapses. Additionally immunohistochemical studies indicate that the SON is the likely source of the glycinergic transmission and that terminals that release glycine also co-release GABA (Coleman et al. 2011).

Publications

Coleman WL, Fischl MJ, Weimann SR and Burger RM.  GABAergic and glycinergic inhibition modulate monaural auditory response properties in the avian superior olivary nucleus.
J Neurophys. 2011 May;105(5):2405-20. Epub 2011 Mar 2..

Fischl MJ, Combs TD, Klug A, Grothe B, and Burger RM.  Modulation of synaptic input by GABAB receptors improves coincidence detection for computation of sound location.
J Physiol. 2012 Jul 1;590(Pt 13):3047-66. [Epub 2012 Apr 2].

Meeting Abstracts

Society for Neuroscience        November 2012
MJ Fischl, SR Weimann, MG Kearse and RM Burger.  Glycine Occludes GABAergic Inhibition in the Avian Sound Localization Pathway.

Pennsylvania Network Meeting - Physics and Chemistry of Biological Systems    
September 2012
MJ Fischl, SR Weimann, MG Kearse and RM Burger.  Glycine Occludes GABAergic Inhibition in the Avian Sound Localization Pathway.

Society for Neuroscience        November 2011
MJ Fischl and RM Burger.  Heterogeneity of Intrinsic Membrane Properties in the Avian Superior Olivary Nucleus

34th Annual Midwinter Meeting of the Association for Research in Otolaryngology     February 2011
MJ Fischl, S Oline, and RM Burger.  GABA and Glycinergic Synaptic Transmission in the Avian Superior Olivary Nucleus

33rd Annual Midwinter Meeting of the Association for Research in Otolaryngology     February 2010
TD Combs, M Fischl, A Klug, and RM Burger.  GABAB Receptor Activation as a Mechanism for Maintaining Precise ITD Selectivity Under Varying Stimulus Conditions: an In Vitro Study.

WL Coleman, M Fischl, D Trause, and RM Burger.  Physiological Heterogeneity in the Avian Superior Olivary Nucleus.

32nd Annual Midwinter Meeting of the Association for Research in Otolaryngology     February 2009
M Fischl, TD Combs, and RM Burger.  Response Characteristics of the Avian Superior Olivary Nucleus.

American College of Toxicology Annual Meeting 2006
L Pratt, M Fischl, J Sallit, B Bowen, GL DeGeorge. Validation of an In Vitro Phototoxicity Test Using 3D Epidermal Tissue Models and Cytokine Endpoints

GL DeGeorge , M. Reeder, CA Kirk, T Ripper, S Litt, M Fischl , B Bowen, DR Cerven. Temporal Stability and Vehicle Effects on α-Hexylcinnamaldehyde Responses as a Positive Control in a Flow Cytometry-based LLNA

American College of Toxicology Annual Meeting  2005
CA Kirk, MK Reeder, TL Ripper, B Bowen, M Fischl and GL DeGeorge, Validation of a Non-       Radioactive Flow Cytometry-based Unscheduled DNA Synthesis (FL-UDS) Assay