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 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.
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 discrimination.
The figure below shows results from a study using the Morris water task to investigate spatial navigation by a novel transgenic rat model of Alzheimer’s disease (TgF344-AD). Data appears in Berkowitz et al 2018.
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 using optogenetics or chemicals such as muscimol, lidocaine, or via chemogenetics.
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.
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.
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 (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.