Modulation of Hippocampal Memory

About

In studying learning and memory mechanisms, we make an important distinction between conditions required for learning (i.e., modulation of learning), and the actual stored content of learning. The conditions of pattern separation can be studied from the perspective of survival systems where emotional arousal is involved, and also from the perspective of reinforcement signals where feedback and prediction error are involved. We use both perspectives to examine the conditions that optimize hippocampal pattern separation and how these conditions change as a function of age.

Projects include:

Emotion Arousal and Hippocampal Pattern Separation

We examined the role of emotional arousal in modulating hippocampal function (cf. McGaugh, 2004) using an emotional pattern separation task (see figure) where valence and interference (i.e., similarity) were parametrically varied. We found that emotion enhanced target recognition but impaired lure discrimination, suggesting that emotion’s enhancing effect was specific to gist information and not details. We also demonstrated that emotional pattern separation was associated with emotional modulation signals in the amygdala and memory signals in the dentate (DG)/CA3. We also found that adults with depressive symptoms were better at discriminating negative lures and worse at discriminating neutral lures, an effect that was associated with a network imbalance where the amygdala’s response was heightened and the DG/CA3 response was suppressed. These results have appeared in two recent papers led by graduate student Stephanie Leal. The first is a behavioral paper in Neurobiology of Learning and Memory and the second is a high-resolution fMRI paper in Hippocampus.

Emotional discrimination task. During encoding, participants rated images according to their emotional valence (using three buttons for negative, neutral, and positive). Each image was presented for 2500ms with a 500ms inter-stimulus-interval (ISI). After a 5- minute delay, participants underwent a surprise recognition test where they viewed negative, neutral, and positive targets (exact repetitions), foils (new items), and lures (similar items) and were asked to indicate whether items were “old” or “new”. 

Noradrenergic Arousal in Hippocampal Memory Processes

Imagine you are on a hike and all of the sudden standing on the trail in front of you is a 400-pound grizzly bear. How do you react? What will you remember about this experience? What does your brain do to ensure that the next time you are on the trail you should be aware of this scary and frightening possibility?

There is a large literature suggesting that norepinephrine, the neurohormone released during a “flight-or-flight” response (such as encountering a bear), is involved in the formation of emotional memories. Research primarily done in rodents and pioneered by Distinguished Emeritus Professor Dr. James McGaugh suggests that the formation of an emotional memory is driven by noradrenergic drive within specific components of your brain, namely, the amygdala.

Consistent with this, research conducted at UCI in humans has provided converging evidence using a non-invasive salivary biomarker for noradrenergic activity: salivary alpha- amylase (sAA). This research has shown that increased levels of sAA as a result of viewing negative or threatening images is positively correlated with performance on a subsequent object pattern separation task. In a separate investigation, elevated levels of sAA predicted enhanced memory performance for negative but not neutral items. Taken together this body of work suggests that during your bear encounter one major facilitator of memory consolidation for emotional events is noradrenergic drive to the basolateral amygdala.

While these data suggest that noradrenergic drive plays a critical role in emotional memory, they do not offer an understanding of how this process may be altered in depression, which presents with both enhanced emotional memory for negative information and monoamine depletion.

Our lab is currently investigating how transient changes in noradrenergic drive amounts in various phases of encoding, consolidation and retrieval of emotional memories in healthy and depressed individuals.

Impact

Future Studies

Project Team

Gimarie Martínez 
Graduate Student