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Research Themes



Our research interests are in neural development, plasticity, and sensory processing. Nervous systems require a high level of organization and precision, as each neuron is itself a complex 3-dimensional entity that may receive anywhere from 1 to over 300,000 inputs (synapses) from other neurons. Individual neurons interacting with other neurons to perform specific tasks make up neural circuits. Within a neural circuit, the type, location, and strength of each of the synapses connecting the neurons determine the quality and range of tasks the circuit can perform.

The precision achieved by neural circuits is neither hard-wired nor randomly acquired. Rather, this precision is attained through an interplay of environmental and genetically-determined factors during an early developmental period. While the specific task to be performed and the timing of the early developmental period vary with brain area, a common theme for circuit refinement throughout the nervous system is that neural activity (whether spontaneously generated in the nervous system or driven by external stimuli) directs biological mechanism (ie., specific proteins and cellular processes) to modify neural circuits (plasticity). Neuroscientists refer to this process as "activity-dependent plasticity." Our aim is to understand the rules and mechanisms by which immature neural circuits are refined, especially those mechanisms related to activity-dependent plasticity and to the coordinated refinement of excitatory and inhibitory circuits.

We study how neural circuits are refined during early life--and how circuit precision contributes to sensory processing--in the mammalian auditory system, with a current focus on the lateral superior olive (LSO). This brainstem nucleus plays a central role in auditory processing and is critical for sound localization and extracting signal from noise, key elements of auditory perception and attention. The LSO is part of a larger auditory processing circuit, the superior olivary complex (SOC), depicted below.

To localize sound sources along the azimuth, many species use differences in sound arrival time and intensity between the two ears; in mammals these interaural differences in phase and intensity are computed in the SOC. In particular, large neurons in the mammalian LSO "add" two inputs that both encode sound intensity:  a positive (excitatory, glutamatergic) input from the ear on the same side and a negative (inhibitory, glycinergic) input from the other ear. To reliably compute these interaural intensity differences, the LSO cells require inputs with precise tonotopic (frequency-based) alignment. A major task for the developing brain is to establish and refine the "circuit diagram" of the LSO so that individual LSO cells receive inhibitory and excitatory inputs that correspond to the same sound frequency.

We work at the interface of cellular and systems neuroscience. Current research directions in the lab concern the nature and function of GABA, glycine, and glutamate co-transmission during development, specification of synapse position during development, information encoded in early spontaneous activity in the auditory brainstem, and mechanisms of developmental/synaptic plasticity in the LSO.



Schematic diagram: major nuclei of the (rat) superior olivary complex in cross-section (coronal)


SOC_schematic


Like most neural structures, the auditory brainstem is bilaterally symmetric; for clarity, only one side is labeled here. The medial superior olive (MSO) is primarily responsible for computing interaural timing differences, the LSO for computing interaural intensity differences. The major inputs to the LSO are the excitatory (green) input from the ipsilateral anteroventral cochlear nucleus (AVCN), a glutamatergic projection, and the inhibitory (red) projection from the ipsilateral medial nucleus of the trapezoid body (MNTB). The inhibitory MNTB-LSO projection carries information from the contralateral ear; though it is glycinergic in the adult, it uses GABA, glycine, and glutamate during the period of major circuit refinement.



Technical Approaches



Lab techniques:

Patch-clamp electrophysiology (living brain slice)
Extracellular single-unit electrophysiology (in vivo)
Tract-tracing
Immunolabeling
Laser-scanning confocal microscopy
Cell fills (cellular morphology)
3-D neuronal reconstruction




Research Support



We are grateful for past and/or present support from the following sources:

CIHR (Canadian Institutes for Health Research)
  New Investigator Award
  Operating grant
CFI (Canadian Foundation for Innovation)
  Infrastructure funds
Ontario MRI (Ministry of Research and Innovation)
  Early Researcher Award
  Infrastructure funds
NSERC (National Science and Engineering Research Council)
  Discovery grant