André A. Fenton

Biography

André A. Fenton is Associate Professor in the department of Physiology and Pharmacology at SUNY Downstate Medical Center, United States of America.

Research Interest

The impressive progress in brain research has produced a substantial gap between our detailed knowledge of the molecular and cellular interactions in the brain and the mental processes that these interactions give rise to. Our research aims to bridge this gap by focusing on the systems-level physiology of the hippocampus. The goal is to learn how a neural system coordinates the activation of the momentarily relevant representations it has stored while suppressing the activation of momentarily irrelevant representations. Behavioral models of cognition, pharmacological, electrophysiological, and computational techniques are employed to understand how operations of the hippocampal system are related to the details of spatial behavior and its modulation by learning, attention, and stress. For example, by studying the information that rats use to navigate, we learned that they form multiple memories of places, and that these memories are organized in distinct spatial reference frames corresponding roughly, to the “room” and “floor” (Fenton et al., 1998). This is analogous to how people riding the bus understand where they are on the bus as well as where they are in the city. Using drugs to permanently or temporarily inactivate parts of the hippocampus, we found that without a functioning hippocampus, rats cannot coordinate the two representations of the room and the floor (Cimadevilla et al., 2001; Wesierska et al., 2005). This work used active place avoidance task variants that were developed as a sensitive set of assays for hippocampal dysfunction. We recently used the task to demonstrate that the same molecular mechanism (PKMzeta) that maintains LTP in the hippocampus also maintains hippocampus-dependent memory. Inhibiting PKMzeta activity in the hippocampus returned long-term (22-hr) potentiated synaptic transmission to baseline values and dramatically erased long-term (1 day-old) and remote (30 days-old) place avoidance memories (Pastalkova et al., 2006) without impairing baseline synaptic transmission or the ability to learn and remember a new place avoidance. Using a variety of other memory tasks we have now confirmed that the persistent activity of PKMzeta is a general mechanism for storing the precise information that is crucial for both appetitively and aversively motivated memories of specific, accurate learned information, but is not required for processing contextual, imprecise, or procedural information (Serrano et al., 2008).