Cholinergic Gain Control and the Short-term Dynamics of Cortical Synapses

New York University, New York NY

Investigators

Abstract

Nerve cells (neurons) in the brain form a network that processes input from the sense organs, creating an internal representation of the outside world. The flow of information through the network depends on behavioral state: for example, processing of sensory input is enhanced when an animal is awake, and suppressed during sleep. Each neuron forms thousands of connections (synapses) with its neighbors, and when the brain switches between behavioral states there must be coordinated changes in the strength of the connections. How this happens is not fully understood. The proposed study examines the role of acetylcholine (ACh), a natural substance that permeates the brain and seems to promote wakefulness and alertness. ACh is known to affect synapse strength as well as other properties of neurons. The goal is to understand how the effects of ACh at the cellular level translate into enhanced processing of sensory input during wakefulness. In particular, the work will address the question of how ACh-dependent synaptic changes interact with short-term synaptic dynamics (rapid, reversible changes in connection strength that depend on the recent activity of each neuron) to influence sensory processing. The experimental approach will involve computer simulations based on pharmacological data obtained from living brain tissue. First, electrical recordings will be made from pairs of connected neurons in brain tissue from rodents. The tissue will then be exposed to ACh in order to test its effect on synaptic strength and dynamics. A computer will be programmed to simulate a network containing different types of interconnected neurons, with synaptic connection strengths and dynamics derived from the experimental results. Simulated sensory input will be fed into the computer, to test how it is transformed (for instance, amplified or degraded) as it is propagated through the network. By changing the parameters (simulated connection strengths and dynamics) of the model, it will be possible to test the hypothesis that ACh acts as a global switch controlling sensory amplification (gain) in the network. This will be the first model of ACh action that incorporates different cell types with realistic short-term dynamics, factors that are critical for sensory information processing in real brains. The principal investigator has worked with high school, undergraduate, and graduate students, both as a project mentor and on an ad-hoc basis. In conjunction with the NYU Department of Teaching and Learning, he has presented his ongoing research to teachers from local schools whose students are predominantly from disadvantaged minority groups, with very limited research opportunities. The proposed research includes components that will serve as stand-alone projects for students and/or teachers from the latter group, or for high school students in the Siemens science competition, NYU undergraduates, and participants in the Summer Undergraduate Research Program, which gives priority to women and under-represented minorities. The principal investigator also participates in the course run by the NYU School of Education, which informs local pre-college teachers about current research.