PI: Jyothi Arikkath, PhD
Project Title: A Device for Photostimulation of Live Neurons
Grant Agency: NSF, University
Neurons form connections with each other at points of contact called synapses. The maintenance of synaptic number and function is vital in the ability of the brain to perform higher order functions, including learning and memory. Several neurodevelopmental and neurodegenerative disorders are associated with alterations in synaptic numbers. Recent studies in mouse models suggest that restoration of the synaptic number in some of these disorders may have therapeutic benefits. However, very few drugs that control synaptic number have been identified and characterized and even fewer are in the clinic. The main impediments to drug screening paradigms in neurons has been the availability of cell lines that recapitulate neuronal structure and function and the availability of image processing software that allows for high throughput image screening and analysis.
In this proposal, we propose a collaborative effort to (1) screen and validate a small molecule library for compounds that control synaptic number in a primary neuronal cell culture system that faithfully recapitulates neurons in vivo (2) develop an imaging algorithm for assessing various neuronal parameters that can be extended to high throughput screening. In the long-term, we expect these studies to (1) lead to the establishment of a start-up company in the state of Nebraska that provides drug screening and other related services in neurons and related cell types (2) provide some small molecule targets for neurological disorders that can be further validated before clinical trials (3) provide a pipeline for drug discovery for a variety of neurological disorders.