Lisa Goodrich, PhD

Animals are able to detect, perceive, and react to a wide range of stimuli in their environment. Although sensory information always flows from peripheral sensory organs into the central nervous system, each system exhibits specialized features, highlighted by differences at the circuit level. For instance, in the cochlea, sound information is organized according to frequency and must be communicated with exquisite speed and precision, thereby permitting animals to localize sounds based on miniscule differences in timing. In the retina, on the other hand, a wide variety of neuronal subtypes cooperate to detect and encode aspects of the visual scene, such as the onset of light or direction-selective motion. Accordingly, neurons in the cochlea and retina exhibit fundamentally distinct morphologies and patterns of connectivity. 

Spiral ganglion neurons (SGNs), the primary sensory neurons of the inner ear, have quite simple bipolar shapes, with unbranched peripheral processes projecting like spokes of a wheel out to sensory hair cells in the organ of Corti and central processes forming the eighth nerve, which projects in a tonotopic fashion to the cochlear nucleus complex in the auditory brainstem. Although grossly similar in morphology, SGNs vary in their intrinsic properties, with some showing low spontaneous firing rates and others showing much higher spontaneous firing rates, likely improving the ability to detect sounds across a wide dynamic range and in a noisy environment.

Retinal neurons, on the other hand, are celebrated for their diverse shapes, particularly evident in the amacrine cells, a population of interneurons that modulate the flow of information from the photoreceptors to the retinal ganglion cells, which are the primary sensory neurons for vision. Whereas sound frequency dictates order in the cochlea, in the retina, neurons are organized by identity, with subtypes of neurons forming cell-type specific microcircuits within defined regions of the neuropil. Although cochlear and retinal circuits are obviously different in many ways, they are somehow created using the same basic sets of molecules and cellular mechanisms that operate across the developing nervous system.

In the Goodrich laboratory, we are using molecular genetic approaches in the mouse to understand how different types of neural circuits are assembled, investigating both the cellular mechanisms (i.e. using time lapse imaging and anatomical analysis) and the molecular mechanisms (i.e. using single cell and bulk transcriptome analysis, biochemistry, and generation of new mouse mutants, including CRISPR/cas-9 generated point mutant alleles). Please see our laboratory website, http://goodrich.med.harvard.edu/, for more detailed descriptions of our current projects.

"We are using forward and reverse genetic approaches in the mouse to understand how genetic mutations lead to changes in the perceptions of hearing and balance."