Every day we make decisions to best meet our needs. Using environmental cues and our past experiences, we prospectively consider the outcomes of our potential choices to select appropriate behaviors. Accurate prospective considerations are crucial to adaptive decision making, so it is critical to understand the neural circuits behind them. The basolateral amygdala (BLA) is a hub for associative reward memory that is well connected with cortical regions such as the anterior cingulate cortex (ACC). The ACC mediates aspects of decision making, including allocating effort and attention. Thus the ACC-BLA circuit is potentially important in coordinating memory retrieval to support reward-related decision making. We tested the hypothesis that activity in projections between the BLA and ACC enables rats to use associative memories to guide reward seeking and value-based decision making behaviors appropriately. We used temporally-restricted, pathway-specific chemogenetic inactivation of either the ACC→BLA or BLA→ACC projections during tests in which subjects must use cues to predict rewards and their value to make decisions. Our preliminary results show that activity in the ACC→BLA, but not BLA→ACC pathway, is needed for reward cues to inform reward-seeking decisions. We also found that the BLA→ACC, but not ACC→BLA pathway, is important for using cue-reward memories to retrieve current outcome value to guide behavior. This research adds to our knowledge of how the brain supports healthy decision making, and can inform research into how maladaptive decision making may arise in psychiatric illnesses such as substance use disorder.

Dementia with Lewy bodies (DLB) is a progressive disease that hinders cognition, disrupts sleep, and causes neurodegeneration due to aggregation of the α-synuclein protein. Studies show that synchronizing gamma-band activity in neuronal networks using 40 Hz light and auditory stimulation can trigger the brain’s immune cells, microglia, to eliminate dementia-inducing proteins, thus mitigating dementia symptoms in mouse models of Alzheimer’s disease. Musical stimulation in particular has proven beneficial for behavior in dementia patients, but the mechanisms and effect on cognitive abilities are largely unknown. In this study we aim to test whether music improves cognition as well as sleep in mice with DLB. We hypothesize that exposure to music with enhanced 40 Hz cycles will activate a microglial response that reduces the accumulation of α-synuclein in the brain. This study is still in its early stages, but we plan to expose mice with DLB to various combinations of visual and musical 40 Hz stimulation and measure its effects using cognitive assessments, encephalogram recordings, and microglia and α-synuclein assays. For the groups exposed to the music with enhanced 40 Hz cycles, we expect to see improvements in cognition, increased stability in brain activity during sleep, and decreased α-synuclein presence coupled with the activation of microglia in numerous brain regions. These results will demonstrate that music can be manipulated to trigger an immune response that attenuates the symptoms of DLB in mice, and, in time, this revelation could also lead to breakthroughs in human dementia treatment.

Like human babies learning to speak, juvenile songbirds learn to vocally imitate songs by practicing copying their tutors’ songs during developmental critical periods. To investigate this process, pupils’ songs are analyzed at regular intervals during the progression between subsong (20 days post-hatch), plastic song (30 days post-hatch), and crystallized song (90 days post-hatch). However, manually curating and recording song types and learning styles for each interval is time-intensive. To overcome this, we adapted an algorithm developed for parrots so that it can be used for zebra finches using the coding program R Studio. We assessed a series of song recordings from pupils injected with a viral construct designed to interfere with miR-128, a brain-enriched micro-RNA, and sibling controls injected with a non-targeting construct. We hypothesized that this manipulation would enhance vocal learning by prolonging the critical period for crystallization and that the machine learning algorithm would capture vocal learning strategies not observed using the traditional analysis program, Sound Analysis Pro (SAP) due to limitations within the program. By evaluating differences between the algorithm and SAP and determining the effect of viral intervention, we aim to provide a qualitative view of the pupil and tutor relationship and see whether and how disruption of miR-128 enhanced a pupil’s ability to mimic its tutor.

The cap binding complex (CBC) binds to the 5’ cap structure of the nascent RNA and plays an important role in multiple steps of gene expression pathways. CBC is composed of two different proteins: Cbp80 and Cbp20. The large subunit CBP80 contains an intron, however, how the splicing of the intron plays a role in its function is still unknown. Previous research in the lab showed that translation can begin at multiple points of the gene including in the intron. In this research, the functions of the proteins that are produced from different isoforms of the CBP80 gene have been explored. The branch point on the CBP80 intron was mutated to create a non-spliced form of the gene (ns) which is then transformed into cbp80∆ yeast cells to study the function of protein translated from intronic ATG. Interestingly, the growth analysis showed that nsCBP80 can rescue the growth defects of the cbp80∆ cells. This result shows that the non spliced form of the gene is still capable of being translated into a protein that is beneficial to the cell. To follow up, we are working on generating CBP80∆ strains with the cDNA form of the gene. The growth of this strain can then be compared to the nsCBP80 and cbp80∆ cells. Altogether, this study showed an interesting role of the CBP80 intron in regulating its function.