Neurobiology of Learning and Memory

Stressful and emotionally arousing experiences create strong memories that seem to lose specificity over time. It is uncertain, however, how the stress system contributes to the phenomenon of time-dependent fear generalization. Here, we investigated whether the glucocorticoid hormonal system affects the specificity of contextual fear memories at several timepoints. We trained male Wistar rats on the context fear conditioning (CFC) task using two footshock intensities (mild CFC, 3 footshocks of 0.3 mA, or moderate CFC, 3x 0.6 mA) and immediately after the training session we administered corticosterone (CORT-HBC) systemically. We first tested the animals in a novel context and then in the training context at different intervals following the training (2, 14, 28 or 42 days). By contrasting freezing times shown in both contexts, we inferred contextual fear generalization for each rat. Following mild CFC training, the glucocorticoid induced the consolidation of an increased discriminative contextual memory that lasted from two up to 28 days. In contrast, after moderate CFC training, CORT-HBC elicited contextual generalization at 14 days, contrarily to the control group that maintained contextual discrimination at this timepoint. For this training intensity, however, CORT-HBC did not have any effect on recent memory specificity. These findings indicate that manipulating glucocorticoid levels after mild or strongly arousing experiences may differentially modulate memory consolidation and time-dependent fear generalization, possibly suggesting there may be a minimum level of emotional arousal that is necessary for CORT-HBC to modulate the creation of generalizable fear memories.

Raw data describing the effects of post-fear extinction wheel running on fear extinction retrieval, fear renewal, and pS6 levels in various brain regions.

Study Abstract: Sleep is vital for biological function and long-term memory formation, with preferential enhancement of emotionally laden content. A growing trend in healthy young adults is the off-label use of psychostimulants, or “smart drugs”, to prevent sleep and, hopefully, enhance cognition. However, the effect of these drugs on sleep-dependent memory processes are unclear. Here, in a within-subject, double-blind, placebo-controlled design, we investigated the impact of morning administration of dextroamphetamine on memory retention of negative and neutral pictures after 1) 12 hours of wake, and 2) 24 hours with sleep. After 12-hrs of wake, stimulants demonstrated a 6% boost in memory for neutral, but not negative, pictures, compared to placebo. In addition, stimulants impaired nighttime sleep and resulted in a 12% reduction in memory for neutral pictures at 24-hrs, compared to placebo. Again, no performance differences between drug conditions were found for negative pictures. Together, these findings suggest that stimulants provide a fleeting recognition memory boost during the day, but their impairment of nighttime sleep likely leads to next day memory costs.

Raw data of mice (EHMT1 KO vs WT) in Object Space Task

Here, we developed an approach to examine the effect of adding training trials or spacing on memory and used genetic and behavioral manipulations in Drosophila to examine the mechanismos involved.

simulations of the cerebellum investigating homeostatic plasticity

step through latency in inhibitory avoidance task Rats given systemic injections of saline or lactate or HCAR1 agonists pretraining or post training in an inhibitory avoidance task and step through latencies were measured 48 hrs after training

Fear conditioning data for mice upon CA2 activation or inhibition and for RGS14 KO mice.