Hippocampal Networks and Episodic Memory
Abstract
People routinely organize the flow of events into distinct episodes when dealing with the complexity of dynamic environments. Such episodic memories incorporate information about the identity of items, their spatial locations, and the order in which they occurred(#what#, #where#, and #when#). Understanding how the cortical telencephalon processes episodes is thus a basic issue in contemporary neuroscience and one that is central to the development of autonomous systems that can deal with the real world. The hippocampus is critical for acquisition and retrieval of episodic memories but there are no models relating the components and operations of the structure to the multiple and diverse aspects of this singularly rich form of encoding. This in large part reflects a surprising absence of information about input/output relationships of the primary hippocampal circuit. However, studies in this program showed that signals from entorhinal cortex generate a two-part response in the output stage of hippocampus (field CA1) that is triggered by dual sub-circuits. Signals are routed through the two pathways according to the frequency of the arriving cortical pulses. Our studieshave also identified novel filters and amplifiers throughout the complex circuit along with a potent excitatory feedback system that is critical to throughput. Finally, we were able to show that certain of these subsystems are essential to acquisition of the #what, #where#, and #when# elements of an episode. These results enabled the construction of realistic simulations to address specific issues but there are major issues that prevented the development of a model capable of generating the diverse aspects of episodic memory. The proposed work addresses these problems. The first goal is to describe circuit responses to input from the spatial subdivision of the entorhinal cortex alone, or in combination with the non-spatial subdivision (the latter has been used in our studies to date). Our second goal is to identify the cellular mechanisms that underlie the unusual low pass filter in the CA3 field: studies will test proposed roles for feedforward inhibition from somatostatin-positive interneurons. Other Aim 2 studies will determine if field CA2 acts as an intermediary filter between CA3 and CA1. The third set of studies will test the influence of modulatory inputs, with special emphasis on the cholinergic afferents, on frequency filtering, amplification and feedback within the hippocampal circuit. Studies addressing the second the third goals make use of powerful chemo- and opto- genetic approaches to selectively manipulate specific cell types and afferents. The activity patterns and rhythms typically present in hippocampus are known to produce learning-related change in synaptic strength and a realistic model will accordingly require information on changes in circuit function arising from such plasticity. Thus, the fourth goal is to test for activity-induced changes in synaptic function at specific nodes # thisstudy will constitute a first test for circuit level plasticity. The final goal is to build a model of primary hippocampal circuitfunctions. These studies, to be conducted in collaboration with Dr. Richard Granger (Dartmouth) will both integrate the disparate operations of the circuit into the model and be used to develop hypotheses about how these operations relate to the processing of episodic memory. [Approved for public release.]
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 21, 2023
- Source ID
- N000142412014
Entities
People
- Gary Lynch
Organizations
- Office of Naval Research
- United States Navy
- University of California, Irvine