The cognitive timeline: The role of the hippocampus in reducing interference

Funding Round: 1 2013-2015

Research Question: This project investigated how the brain learns information presented sequentially and protects memories of events that occurred close in time from interference with each other.

Interdisciplinary Approach: The research combined neurophysiological recording studies of laboratory rats with functional imaging of human subjects to bridge the gap between animal and human studies of learning.  An engineering approach provided sophisticated quantitative analyses to both sets of studies.

Potential Implications of Research: This research provides important insights into the neural mechanisms underlying learning and memory, which may lead to better treatments for patients with memory loss as well as improved methods for promoting the learning of new information that occurs close in time.

Project Description: The ability to place memories in time is an important facet of our understanding of the past and present, and it is a critical feature of our ability to make predictions about the future based on prior learning.  We do not know how the brain is able to remember when events happened, but the way our brain processes when events happened in time appears similar to the way it processes where events happened in space. One problem the brain faces is that events that occur close together in time may be very similar and therefore it may be difficult to remember their order later (e.g. “did I put sugar or creamer into my coffee first this morning?”). To study this question, we designed a novel task that tested people’s memory for the order of objects in a sequence.  We found that participants remembered the order of two objects better when they appeared further apart in the sequence (e.g. the first item vs. the last item) than when they occurred closer together in the sequence (e.g. the 12th item vs. the 13th item). To investigate how the brain might be processing temporal information, we used high-resolution neuroimaging while individuals performed this task (Fig. 1).  We found greater activity in the medial entorhinal cortex (MEC), a brain region involved in spatial processing, when participants were trying to remember the order of objects that were closer together in time (the more difficult judgment). Furthermore, we found greater activity in the MEC and the hippocampus (a brain region critical for memory) when participants were able to remember the order of the objects than when they were not. These findings shed new light on how we remember when events happened in time, particularly when the remembered events occurred close to each other in time.

We also recorded the activity from 4 regions of the rat brain that are known to be critically involved in learning and memory while the rats performed a temporal odor discrimination task similar to the task used by the human subjects. We found that a number of neurons in the hippocampus and entorhinal cortex responded to specific odors. Importantly, a fraction of these cells appeared to fire more strongly when the odors occurred in a specific temporal position within the sequence.  Other cells changed their firing properties over time in ways that suggest that they encoded the passage of time in the learning trials. These properties may provide the neural basis for encoding memories over time, allowing the brain to keep track of which events occurred earlier in a sequence and thus enabling the animal to learn and remember unique sequences of events.