Loren Frank, Ph.D.

Learning in the Hippocampus and Cortex

Previous studies have shown that neurons throughout the hippocampal formation show place specific firing patterns, where a given neuron is active only in a subregion of the animal's environment. Most of these studies focused on describing patterns of activity during well learned tasks, and we therefore know little about neural processing during learning. The Frank lab developed a spatial alternation task that animals can learn over the course of a few days of exposure. This task provides a powerful paradigm for examining the relationship between dynamic patterns of neural activity and changes in behavior.

Although the hippocampus is essential for spatial learning, storing and retrieving new information requires complex networks spread throughout the brain. One prominent hypothesis states that learning takes place first in the hippocampus and over time information is transferred to neocortical regions in a process known as consolidation; therefore, recording both in the hippocampus and downstream to understand how hippocampal and cortical circuits could support learning, consolidation and memory guided behavior.

These studies continue to provide important new insights into how the brain changes as animals learn and how memory retrieval might occur, but these insights are fundamentally correlational in nature. We have therefore been developing and apply new techniques, including optogenetic manipulations, to take these correlational hypothesis and turn them into causal understanding. We can now express optically activated channels in specific subpopulations of neurons in the rat hippocampus and activate these channels with an implanted fiber optic. We have also combined this optical activation with large scale multielectrode recording, allowing us to manipulate the circuit and record the results both locally and in more distant brain regions.
Anatomical Organization of the Hippocampus

The hippocampal formation has a unique anatomical organization in that the connectivity between adjacent hippocampal regions is almost exclusively unidirectional. The majority of neocortical input to the hippocampus comes in through the superficial layers of the entorhinal cortex and connections proceed through the dentate gyrus, to CA3 and on to CA1 (the hippocampus proper), and then to the subiculum. Nearly all neocortically bound outputs from the hippocampus originate in CA1 and the subiculum and target cells in the deep layers of the entorhinal cortex, which projects both to numerous neocortical regions as well as to back to the superficial layers of the entorhinal cortex. research uses that organization to compare patterns of activity across regions and to use the similarities and differences among the patterns to identify the transformations that occur in the hippocampal circuit.

An Animal Model for Hippocampal Function

Numerous researchers have shown that a human without a hippocampus is unable to form new memories of facts or events. In rodents these same structures play an essential role in animal's abilities to learn about and remember complex associations, including tasks where the animal must learn and remember information about a set of spatial cues in order to navigate through an environment. Event/fact memory in humans and spatial memory in rodents both require learning complex relationships, and that parallel strongly suggests that qualitatively similar processing occurs in the human and the rat hippocampus.