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Quantitative Approaches to Systems Neuroscience

Research Summary

Carlos Brody studies the neural mechanisms underlying cognition by fusing computational modeling with experimental neuroscience.

What Are We Interested In?
Here's an example: you're browsing in a store. You see an item you like, perhaps you might buy it, but you're not sure yet. You stroll further, and see a second item. You compare them; perhaps today you decide to buy the first. What happened in your brain as you went through all this? What are the neural mechanisms that allow you to remember, for a few seconds, how much you liked the first item; to compare the two items; to make a decision; to apply the rules of behavior appropriate for the context you're in (a store in this example)? In other words, what are the neural mechanisms underlying your cognitive abilities?

Figure: A decision-making task requiring accumulation of evidence over time.

What Methods Do We Use in Our Research?
We use a combination of computational, behavioral, optogenetic, pharmacological, and electrophysiological techniques. We train rats to perform tasks that require cognitive components that we're interested in studying. For example, we train them to remember a stimulus for a few seconds, they then compare it to a second stimulus and make a decision based on that comparison. Among other cognitive processes used in the task, correct decisions require remembering the first stimulus in the delay between the two stimuli. This allows us to study the neural basis of short-term memory. To help us understand our experimental findings, we build computational models of networks of spiking neurons, with which we explore the circuit architectures and mechanistic hypotheses that could explain the experimental results. The models give us greater insight into potential mechanisms and help us to decide the best next experiments to test and distinguish between hypotheses.

The Specific Cognitive Processes and Behavioral Tasks We Are Studying
The three main behavioral tasks we are currently using in the lab correspond to three main cognitive processes of interest:

Decision making. Rats hear two trains of simultaneously presented, randomly timed auditory clicks: one train coming from a speaker to their left, the other from a speaker to their right. On each trial of the task, the rats must decide which of the two sides had the greatest total number of clicks. This requires an accounting of accumulating clicks over time, so as to compare the two totals, thus providing a rodent model to study one of the core components of decision making, gradual accumulation of evidence over time.

Executive/cognitive control. In the second task, we study how cognitive state flexibly determines appropriate rules of behavior. Rats experience two types of trials, "pro" and "anti". In pro trials, they must orient toward a light to obtain a water reward. In anti trials, they must orient away from a light to obtain a water reward. Which type of trial they will be in is indicated to them before the trial starts; this sets the cognitive stage. When the light is turned on, the rats must use their knowledge of whether it is a pro or anti trial to select which of two opposite sensorimotor rules is the appropriate one to follow. The ability to rapidly switch sensorimotor rules, on a timescale of only hundreds of milliseconds, is one of the hallmarks of cognitive control.

Working memory. In the third major task that we are currently working with, rats are presented with a stimulus; then there is a pause for a few seconds; and after the pause they are presented with a second stimulus. The rats must compare the two stimuli and make a binary decision based on the comparison. (This is our rodent analog of deciding between the two items in a store.) We use this task to study working memory, the capacity to "hold something in mind" for a few seconds, and to manipulate that mental representation.

Grants from the National Institutes of Health and the Human Frontiers Science Program provided partial support for these projects.

As of February 3, 2014

Scientist Profile

Investigator
Princeton University
Computational Biology, Neuroscience