Development and Application of an Optogenetic Platform for Controlling and Imaging a Large Number of Individual Neurons

Date(s):

Location:
Jacobs Hall, Room 4309, Jacobs School of Engineering, 9500 Gilman Dr, La Jolla, San Diego, California 92093

Sponsored By:
Prof. Duygu Kuzum

Speaker(s):
Ali Mohammed
Texas Tech University
Ali Mohammed

Abstract:

The understanding and treatment of brain disorders as well as the development of intelligent machines is hampered by the lack of knowledge of how the brain fundamentally functions. Over the past century, we have learned much about how individual neurons and neural networks behave, however new tools are critically needed to interrogate how neural networks give rise to complex brain processes and disease conditions. Recent innovations in molecular techniques, such as optogenetics, have enabled neuroscientists unprecedented precision to excite, inhibit and record defined neurons. The impressive sensitivity of currently available optogenetic sensors and actuators has now enabled the possibility of analyzing a large number of individual neurons in the brains of behaving animals. To promote the use of these optogenetic tools, this talk integrates cutting edge optogenetic molecular sensors which are ultrasensitive for imaging neuronal activity with custom wide field optical microscope to analyze a large number of individual neurons in living brains. Wide-field microscopy provides a large field of view and better spatial resolution approaching the Abbe diffraction limit of fluorescent microscope. To demonstrate the advantages of this optical platform, we imaged a deep brain structure, the Hippocampus, and tracked hundreds of neurons over time while mouse was performing a memory task to investigate how those individual neurons related to behavior. In addition, we tested our optical platform in investigating transient neural network changes upon mechanical perturbation related to blast injuries. In this experiment, all blasted mice show a consistent change in neural network. A small portion of neurons showed a sustained calcium increase for an extended period of time, whereas the majority lost their activities.   Finally, using optogenetic silencer to control selective motor cortex neurons, we examined their contributions to the network pathology of basal ganglia related to Parkinson’s disease. We found that inhibition of motor cortex does not alter exaggerated beta oscillations in the striatum that are associated with parkinsonianism. Together, these results demonstrate the potential of developing integrated optogenetic system to advance our understanding of the principles underlying neural network computation, which would have broad applications from advancing artificial intelligence to disease diagnosis and treatment.


Speaker Bio:
Ali Mohammed received his Bachelors of Science degree in physics from Helwan University in Cairo, Egypt, and then his Master of Applied Physics degree from Texas Tech University working in the field of ultrafast nonlinear laser spectroscopy by using optical heterodyne optical kerr effect to study ionic liquids. He then shifted his academic focus towards neuroengineering and began his Ph.D. at Boston University under Dr. Xue Han. His thesis is focused on implementing imaging technique and using optogenetics platform to investigate neural circuitry in cognitive paradigm and disease model as traumatic brain injury and Parkinson’s.

Contact:
Travis Spackman
tspackman@eng.ucsd.edu