What We Do

Neural Mechanisms of Spatial Behavior

To study the neural correlates of spatial navigation, we make use of techniques that allow monitoring of large numbers of neurons simultaneously (10s to 100s) while animals are engaged in specific spatial behaviors. To do this, trainees fabricate electrode arrays composed of tetrodes (four wires twisted together), allowing tetrodes to be adjusted to a specific anatomical target. Neural signals are correlated with behavior in spatial navigation and memory tasks.

Place cell, grid cell, border cell, and head direction cell plots below are courtesy of work by graduate students, Ryan Harvey and Laura Berkowitz.

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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.

The figure below shows cannulation placement in the anterior thalamus and behavioral performance by rats in the radial arm maze after saline or muscimol infusion. Data appears in Harvey et al 2017.

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The figure below shows grid cell and head direction cell activity before and after lidocaine infusion into the anterior thalamus. Data appears in Winter et al 2015.

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Neurobiology of Spatial Disorientation in Alzheimer’s disease

The Clark lab is interested in the neurobiological changes in Alzheimer’s disease that accompany impairments in spatial navigation. Towards this aim, we have recently characterized the spatial behavior of a novel transgenic rat model of Alzheimer’s disease (TgF344-AD) in the Morris water task. We have determined that deficits in the accuracy of swim trajectories (i.e., both the directional and spatial specificity of swim paths) by transgenic AD rats is expressed between 7 and 10 months of age. Data below appear in Berkowitz et al 2018.

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Neural Basis of Memory Deficits in Fetal Alcohol Spectrum Disorders

A recent focus of the Clark lab is in the investigation of neurobiological changes corresponding memory decline in Fetal Alcohol Spectrum Disorders. Our recent work has shown that animals exposed to a moderate amount of alcohol prenatally can accurately perform sensory discriminations between complex objects, but are impaired when required to discriminate between objects on the basis of spatial location in the environment. Data below appear in Sanchez et al 2019.

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Contributions of Altered Functional Connectivity in Age-Related Cognitive Decline

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 (green), within the prefrontal cortex. Cholera toxin labeled cell bodies (green), co-labeled with Arc immediate early gene expression (red) are shown in CA1, perirhinal cortex, and prefrontal cortex. This work is being done in collaboration with Dr. Sara Burke and Dr. Andrew Maurer at the University of Florida. Data from Hernandez et al 2018.

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