What We Do

Systems Neuroscience of Spatial Learning and Memory

Our laboratory makes use of several techniques to provide a systems-level investigation of the neural basis of spatial learning and memory. Specifically, 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 that can be adjusted to a specific anatomical targets. Neural signals are correlated with behavior in spatial navigation and memory tasks. We make use of in vivo electrophysiology methods to investigate changes in neural circuits in pre-clinical models of developmental and neurodegenerative disorders. 

Example cell activity from in vivo electrophysiology experiments are shown on the left in the figure below. The true vs. decoded head angle from a population of simultaneously recorded head direction cells is shown on the right in the figure below (from Xu et al 2019).

Cells2


Spatial Memory and Fetal Alcohol Spectrum Disorders

A central focus of the Clark lab is the investigation of neurobiological changes corresponding to spatial memory deficits in Fetal Alcohol Spectrum Disorders (reviewed in Harvey et al 2019). Specifically, 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 (Sanchez et al 2019). Exposure to alcohol prenatally can result in a number of structural and synaptic alterations to hippocampal circuitry (e.g., Madden et al 2020). Consistent with this previous work, we recently found that hippocampal place cell activity is less spatially and directionally specific after moderate prenatal alcohol exposure, thereby pointing to a potential systems-level mechanisms for memory deficits after developmental alcohol exposure (Harvey et al 2020).

FASD


Spatial Navigation, Anxiety, and Alzheimer’s disease

The Clark lab has also been engaged in research investigating the neurobiological changes in Alzheimer’s disease that accompany impairments in spatial navigation and emotional dysfunction (reviewed in Pentkowski et al 2021 and Berkowitz et al 2020). Towards these aims, 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 (Berkowitz et al 2018). In collaboration with Dr. Nathan Pentkowski, we are additionally investigating the neural basis of anxiety-like behaviors which are expressed at the earliest stages of pathogenesis, and precede spatial memory deficits, in the TgF344-AD rat model of Alzheimer’s disease (Pentkowski et al 2018).

watertask