James J. Chrobak - US grants

Lay Abstract (0090451)

The means by which large numbers of neurons (ensembles) effectively
interact is not well understood. Recent findings demonstrate thousands of
hippocampal neurons participating in specific fast-frequency patterns
[theta-modulated gamma (40-100 Hz) and sharp wave modulated ripples (200
Hz)]. These in vivo patterns likely support the memory functions performed
by the hippocampus and interconnected structures (e.g. medial septum).
Local application of drugs into the medial septum of rats will be used to
manipulate both memory formation and hippocampal electrophysiology. This
project will determine the role of septal neurons in regulating gamma and
ripple frequency patterns and the relation between these ensemble patterns
and memory.
The medial septum and the hippocampus are brain structures critical
for episodic memory formation. While the functions supported by particular
brain structures are fairly well understood, how large numbers of neurons
effectively interact to support emergent function is not. The hippocampus
exhibits specific patterns of activity during which thousands of neurons
discharge in transient gamma (40-100 Hz) and ripple (200 Hz) frequency
patterns. These patterns may play a role in organizing the discharge of
individual neurons into ensemble patterns, similar to the manner in which
the precise timing of miniature lights on a large scoreboard can create a
coherent message or picture. What role these organizing patterns actually
play in memory formation is not yet known. This project will manipulate
gamma and ripple frequency patterns, and determine the effect on memory
formation. The results are likely to advance understanding of the
function of fast-frequency ensemble patterns.

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
The hippocampal formation (hippocampus and entorhinal cortex) is essential for making episodic memories in the mammalian brain. The physical substrate of memory resides in the connections among groups of cells (ensembles) and their dynamic activity (electrophysiological) patterns. This project will use a rodent model to address: 1) whether different parts of the hippocampus and entorhinal cortex interact as a single functional group or alternatively work as separate functional groups and 2) the role of specific electrophysiological patterns (theta and gamma rhythms) in defining the activity of a group. Previous studies demonstrated that changes in theta and gamma coherence, a measure of temporal synchrony among neurons, relates to the strength of episodic memory formation and memory retrieval. A key component of the these studies will be how manipulations of the environment (e.g., novelty) alter theta and gamma coherence and whether theta and gamma coherence varies throughout different parts of the hippocampus and entorhinal cortex. This project will provide knowledge about functional interactions between different parts of the hippocampus and entorhinal cortex and how theta and gamma patterns either bring different parts together or segregate them in relation to specific sensory events. This project will also provide; 1) integrative biology training to high school, undergraduate and graduate students interested in psychology, neuroscience and biomedical engineering and 2) a large in vivo electrophysiological database for experimental and computational neuroscientists interested in hippocampal physiology and memory formation.