What We Do

High-Density Electrophysiology in Behaving Animals

Research in the Clark lab makes use of techniques that allow monitoring of large numbers of neurons simultaneously (10s to 100s) while animals are engaged in specific behaviors. To do this, trainees fabricate electrode arrays composed of tetrodes (four wires twisted together), allowing each tetrode to be adjusted to a specific anatomical target. Neural signals are correlated with behavior in spatial navigation and memory tasks. Shown in the figure below is a “hyperdrive” which allows the experimenter to lower tetrodes toward anatomical targets such as the hippocampus. Place cell and head direction cell recordings and analysis courtesy of Ryan Harvey and Laura Berkowitz.

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Rodent Behavior

Our research utilizes a wide range of behavior tasks aimed at assessing animal spatial navigation and memory, including the radial arm maze, Morris water task, open field exploratory behavior, and object recognition. The figure below shows our custom designed radial arm maze (left) as well as results from a platform removal test in the Morris water task (right). Each panel shows an individual rats swim path (orange) in the circular pool (blue outline). Note that swim paths are concentrated around the trained platform location. The swim paths are courtesy of custom Matlab programming by Laura Berkowitz.

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Manipulation of Neural Circuits

To understand the functional relationship between brain structures within limbic circuits and the relationship between limbic circuitry and behavior, our research uses methods that involve the selective disruption of targeted brain regions. These methods include producing brain lesions to specific regions using neurotoxins or reversible inactivation using muscimol or lidocaine. In addition, we have recently begun exploring the use of methods that involve introducing membrane receptors into neural circuits that can be specifically activated or inhibited by light (optogenetics) or chemicals (chemogenetics). The figure below shows the results of recent work from our laboratory showing cannulation placement for muscimol infusion (left), and mCherry expression after micro-injections of AAV-hM4D (chemogenetics) in the anterior thalamus (right).  The work below is courtesy of Ryan Harvey, Shannon Thompson, and Lilliana Sanchez.

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Neuroanatomy and Functional Connectivity

The Clark lab makes use of methods that couple fluorescent neuroanatomical tracing and immediate early gene expression to quantify the functional connectivity between brain regions at a single cell resolution. The figure below shows the results of an injection of the retrograde tracer, conjugated fluorescent cholera toxin-B, within the dentate gyrus of the dorsal hippocampus. Cholera toxin labeled cell bodies, co-labeled with immediate early gene expression (Homer1a and Arc) are shown in the confocal image (40X magnification) on the far right. This work is being conducted in collaboration with Dr. Sara Burke and Dr. Andrew Maurer at the University of Florida.

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