Matt Shapiro, PhD
Professor
Department of Neuroscience Albany Medical College
December 11, 2018
Learning to Remember: Bidirectional Communication Between the Hippocampus and Prefrontal Cortex
Learning and memory formation do not happen in a vacuum, and there is not one brain area responsible for each. Instead, multiple brain regions, connected in circuits, are involved in learning, memory formation, consolidation, and retrieval. Two areas involved in these learning/memory circuits are the hippocampus and the prefrontal cortex. Dr. Shapiro and his lab hypothesized that a certain electrical rhythm, theta rhythm, may provide a way for neurons in this circuit to communicate. Using a rat model, Dr. Shapiro’s lab determined that activity in the hippocampus and prefrontal cortex was coordinated through a theta rhythm produced by the hippocampus. The prefrontal cortex was found to be necessary for learning behaviors that require flexibility, such as following different rules for finding food.
Learning and remembering events require coordinated activity across multiple brain regions, particularly in medial temporal and prefrontal cortices. Circuits in these regions are engaged as memories are acquired, consolidated and retrieved, and damage to these circuits impairs memory, but the neuronal mechanisms that implement memory processing remain known. Understanding how these circuits cooperate during memory processing can help reveal mechanisms of neural communication that are relevant to both memory disorders and to neuropsychiatric illnesses associated with frontotemporal dysfunction, including schizophrenia and affective disorder.
The hippocampus is a medial temporal lobe structure that is crucial for learning and memory-guided decision making. The hippocampus is anatomically and functionally connected to the prefrontal cortex (PFC), a large, heterogeneous, and complex brain region associated with “executive function.” Unlike people with hippocampal damage who remember nothing about recent episodes, people with PFC damage typically remember but have trouble organizing or working with memories, e.g. keeping track of which items belong to different lists.
As animals perform learning and memory tasks, the hippocampus generates rhythmic electrical activity patterns. Theta rhythm, an 8-12 Hz oscillation, coordinates the precise timing of neural excitability in the hippocampus, and thus modulates the synaptic integration required for generating action potentials and inducing plasticity. By orchestrating timing across interconnected brain circuits, theta rhythm may provide a general communication mechanism. In particular, theta rhythm may help coordinate activity in the hippocam pus and the prefrontal cortex on which memory encoding and retrieval depend.
To study hippocampal-prefrontal contributions to memory, we trained rats in a memory task that requires both areas, inactivated one or the other area to identify its contribution to specific cognitive processes, and simultaneously recorded neural activity in both areas. We trained rats to remember which one of two places contained hidden food in a plus-shaped maze, and included a reversal rule, so that after the animal reliably retrieved food from one place, the experimenter placed food in the other and the rat had to “reverse” its choice. Prior work found that hippocampal neurons show prospective activity that predicts spatial decisions, and that disrupting PFC impairs switching between rapidly changing rules. We hypothesized that the PFC supports flexible use of memory by activating appropriate hippocampal representations – the prospective code associated with a particular rule. If theta rhythm helps coordinate frontotemporal communication, then activity in the two structures should be synchronized. We found that theta oscillations were coherent as rats performed the task, and that both hippocampal and PFC neurons were phase locked to the hippocampal rhythm. Moreover, we found that inactivating the PFC did not affect the learning of an initial spatial rule, but disrupted subsequent reversal learning, when animals had to switch from one rule to the other, and thus activate distinct representations. Indeed, inactivating the PFC reduced the separation between hippocampal representations, so that the prospective codes of the two rules were less distinct, suggesting that these ambiguous representations could contribute to impaired rule learning. The results suggest that PFC modulation of hippocampal encoding can reduce proactive interference in memory to support flexible behaviors and decision making in a task with multiple contingencies.