Memory, especially when tied to a traumatic event, can last a lifetime. However, the brain regions important in recalling a memory change over time. The Prefrontal Cortex (PFC), along with the Temporal Association Cortex (TeA), are known to be important for maintaining memories encoded long ago. However, the relationship between these brain regions in support of memory recall has yet to be fully investigated. To examine memories encoded long ago, we utilized cued fear conditioning, in which mice are taught to associate a tone with a foot shock, then tested the memory at a later date by presenting the tone without shock. We employed in-vivo calcium imaging, viral immunostaining, and optogenetic inhibition techniques to parse the activity of PFC neurons connected to TeA during memory recall. We found that PFC neurons which connect with TeA increasingly encode the memory as it gets older. Additionally, silencing PFC neurons active during learning disrupted the recruitment of PFC neurons connected to TeA and the subsequent formation of remote memory. Together, this suggests that PFC’s role in memory is dynamic, recruiting other brain regions, like TeA, to help mediate long-term memory. This discovery can help us understand why traumatic memories from long ago are so persistent, and aid in the development of neurobiological interventions for disorders of maladaptive memory like PTSD.

Decision-making is governed by action-outcome (A-O) associations to guide behavior. Goal-directed strategies, supported by the basolateral amygdala (BLA) and ventral tegmental area (VTA), play a crucial role in reward learning. Dopamine, particularly from VTA projections to the BLA, facilitates encoding outcome value and action-outcome learning. Disruptions to these processes contribute to maladaptive decision-making and neuropsychiatric disorders. Using fiber photometry imaging, we investigate dopamine dynamics in the BLA during Random Ratio (RR) instrumental training to assess BLA dopamine characteristics during learning. In RR training, where reward delivery is unpredictable, strong A-O learning is encouraged, promoting agency and goal-directed behavior. Fiber photometry imaging monitors dopamine release in the BLA of rats as they learn to associate lever pressing with food-pellet rewards. This research aims to advance understanding of dopamine’s role in action-outcome learning and its implications for addressing behavioral disorders. We predicted that during RR training, dopamine release would exhibit increased peak frequency and amplitude during reward anticipation and delivery as animals learn the A-O relationship.

Human induced pluripotent stem cell (hiPSC)-derived brain organoids are increasingly becoming a reliable model to investigate rare neurodevelopmental disorders such as Rett syndrome, which is caused by heterozygous mutations in the MECP2 gene located in the X chromosome. In females, variability in phenotypes and symptom severity can result from random patterns of X-chromosome inactivation that lead to mosaic expression of wild-type and mutant MECP2 alleles in patient brains. To recapitulate this feature of Rett syndrome, we have successfully produced mosaic organoids by intermixing isogenic wild-type control and MECP2 mutant cells, which result in structures that exhibit abnormal neural network activities. To further refine our investigation, we assessed alterations in neurogenesis across wild-type, mutant, and a range of mosaic organoids by quantifying the expression of key markers reflecting distinct populations and developmental states of cells in the developing cortex. Our analysis reveals some significant shifts in the cellular composition across our mosaic models, providing insights into how MECP2 mosaicism might influence early cortical development in patients’ brains. This approach provides a relevant model for the study of the developmental basis of Rett syndrome, deepening our physiological understanding of the disorder.

Theta Burst Stimulation (TBS), a form of Transcranial Magnetic Stimulation (TMS), has emerged as a potential therapeutic intervention for memory-related disorders, including Alzheimer’s Disease and Mild Cognitive Impairment (MCI). This study aims to evaluate whether intermittent Theta Burst Stimulation (iTBS) has the potential to enhance episodic memory. Participants over the age of 55 are recruited and subsequently complete 15 TBS sessions over three weeks, targeting individualized brain regions identified via Functional Magnetic Resonance Imaging (fMRI). To ensure methodological rigor, the study is conducted in a double-blind manner. Episodic memory performance is evaluated regularly using a battery of tasks, including Face Name Association, Verbal Memory Recall, and Object Recognition. Behavioral data is analyzed to assess the efficacy of the intervention. Another method of evaluation includes neuropsychiatric testing that analyzes facets of memory, including psychomotor speed, learning, working memory, and executive functioning. Preliminary neuropsychiatric and behavioral data analysis has been conducted, however, recruitment is currently ongoing to further assess the potential of iTBS as a non-invasive intervention for memory impairment.

Hydra vulgaris is a simple cnidarian with a decentralized nervous system, making it a compelling model for exploring the evolutionary origins of learning. This study investigates whether Hydra vulgaris are capable of associative learning by pairing a neutral stimulus—red light—with a mechanical stimulus delivered via a small vibration motor, which reliably induces a contraction response. Following repeated pairings, we test whether presentation of the red light alone is sufficient to evoke a behavioral response indicative of anticipation, such as full-body contraction or other observed movement patterns. By quantifying behavioral changes over time and contractile responses to the red light pre- and post-conditioning, we aim to determine whether a learned association forms between the two stimuli. Demonstrating such a capability in Hydra would offer valuable insights into the foundations of learning in organisms with simple, decentralized neural architectures and address a significant gap in the current literature on this topic.