BI 243 Alison Barth: Learning as a Window to Cortex
Alison Barth explains how distinct neuron types contribute to cortical function and how learning can be used as an experimental window into the organization and plasticity of cortical circuits.
A fresh look at the bird retina
I am working on the vertebrate retina, with a main focus on the mouse and bird retina. Currently my work is focused on three major topics: Functional and molecular analysis of electrical synapses in the retina Circuitry and functional role of retinal interneurons: horizontal cells Circuitry for light-dependent magnetoreception in the bird retina Electrical synapses Electrical synapses (gap junctions) permit fast transmission of electrical signals and passage of metabolites by means of channels, which directly connect the cytoplasm of adjoining cells. A functional gap junction channel consists of two hemichannels (one provided by each of the cells), each comprised of a set of six protein subunits, termed connexins. These building blocks exist in a variety of different subtypes, and the connexin composition determines permeability and gating properties of a gap junction channel, thereby enabling electrical synapses to meet a diversity of physiological requirements. In the retina, various connexins are expressed in different cell types. We study the cellular distribution of different connexins as well as the modulation induced by transmitter action or change of ambient light levels, which leads to altered electrical coupling properties. We are also interested in exploiting them as therapeutic avenue for retinal degeneration diseases. Horizontal cells Horizontal cells receive excitatory input from photoreceptors and provide feedback inhibition to photoreceptors and feedforward inhibition to bipolar cells. Because of strong electrical coupling horizontal cells integrate the photoreceptor input over a wide area and are thought to contribute to the antagonistic organization of bipolar cell and ganglion cell receptive fields and to tune the photoreceptor–bipolar cell synapse with respect to the ambient light conditions. However, the extent to which this influence shapes retinal output is unclear, and we aim to elucidate the functional importance of horizontal cells for retinal signal processing by studying various transgenic mouse models. Retinal circuitry for light-dependent magnetoreception in the bird We are studying which neuronal cell types and pathways in the bird retina are involved in the processing of magnetic signals. Likely, magnetic information is detected in cryptochrome-expressing photoreceptors and leaves the retina through ganglion cell axons that project via the thalamofugal pathway to Cluster N, a part of the visual wulst essential for the avian magnetic compass. Thus, we aim to elucidate the synaptic connections and retinal signaling pathways from putatively magnetosensitive photoreceptors to thalamus-projecting ganglion cells in migratory birds using neuroanatomical and electrophysiological techniques.
The cellular basis of Parkinson’s disease
Parkinson’s disease is affects millions of people around the world. The disease is characterized by typical movement defects that are caused by the loss of dopaminergic neurons, but several very debilitating non-motor symptoms occur more than 10 years before the motor symptoms. I will discuss how we study these non-motor symptoms including sleep disturbances and olfactory defects using large collections of knock in fruit flies that model the numerous familial forms of Parkinson’s disease as well as using human iPS cells from patients. A common emerging theme are defects in protein homeostasis that in specific neuronal cell types, cause cellular defects that explain the Parkinson-relevant phenotypes. Our work reveals the mechanisms that cause early defects in Parkinson’s disease and it opens therapeutic avenues to start tackling this disease.