Circuit Analysis of Recognition Memory

Brown University, Providence RI

Investigators

Abstract

Mammals, including rats and humans, naturally explore novel items and situations. Exploratory behavior, however, is not optimal in all settings. For example, a hungry animal may avoid exploring a novel item when navigating toward a food source or being pursued by a predator. The perirhinal cortex, part of the medial temporal lobe memory system, is known to be important for identifying novelty. However, how do we know when it is appropriate or safe to explore a novel item or situation? Substantial evidence indicates that such cognitive control relies on the prefrontal cortex. Cells in the prefrontal as well as the perirhinal cortex respond to novelty by changing their activity levels. The mechanisms by which these two, distant brain regions interact in novelty-guided exploration are unknown. Recent work suggests that brain regions communicate by large, low-frequency oscillations, and results from the investigator's laboratory suggest that the particular frequency of oscillation in the perirhinal cortex transmits specific abstract information about the novelty and familiarity of individual items. The present research program addresses the overarching hypothesis that this signaling mechanism between brain regions is used in perirhinal-prefrontal interactions during novelty-guided behavior in rats. The work will impact memory research, neuroscience, and the community at large in several ways. First, the studies promise to delineate the neural mechanisms and brain circuitry underlying recognition memory and novelty-guided behavior. Second, the studies advance our understanding of the role of the prefrontal cortex and of prefrontal-perirhinal interactions in novelty-guided exploration. Finally, the studies hold the promise of revealing a new category of temporal coding in which the frequency of the oscillation enhances the transmission of specific abstract information across brain regions. In addition, the project provides opportunity for students from Historically Black Colleges and Universities to engage in intensive summer research training, and for local middle and high school students to learn about neuroscience research. This research project includes a series of experiments that combine electrophysiology, optogenetics, transgenic animals, and behavior to elucidate the mechanisms and circuits by which synchronous neuronal activity guides appropriate exploration of novelty and familiarity. The experiments test the hypothesis that perirhinal-prefrontal interactions are necessary for novelty-guided exploration and modulated by synchronous neuronal activity in specific frequency bands. In vivo experiments employ multiple measures of rhythmic, synchronous activity to understand the temporal codes relaying information within and between the brain regions as a function of behavior, e.g., changes in local field potential (LFP) power in a given region at particular frequencies, changes in LFP coherence between any given pair of regions at particular frequencies, and phase-locking of cells in one region to the LFP in the same region or in other regions. Complimentary in vitro experiments employ state-of the-art optogenetic tools to interrogate the cellular mechanisms that underlie synchronous activity, focusing in particular on the differential roles of interneurons and pyramidal cells. The results from this work advances our understanding of the underlying circuitry of novelty-guided behavior and cognition, as well as of how brain oscillations modulate cognitive processes.