Serotonergic signaling represents a fundamental component in an understanding of mental illnesses such as anxiety and depression. The serotonin reuptake transporter (SERT) acts as the primary mechanism for clearing serotonin from the extracellular space, and SERT inhibition is currently the largest pharmacological target for antidepressant and antianxiety medications. In order to better understand the effects of SERT, the Drosophila melanogaster SERT allele (dSERT) was mutated through both the use of CRISPR and imprecise excision with transposable elements to create strong hypomorphs of the allele. Serotonin has been shown to regulate sleep in both mammals and flies, thus signaling was characterized in mutants through the observation of different sleep phenotypes: sleep duration, probability of waking, probability of sleeping, and mean activity counts. Subject behavior was monitored through the use of the Drosophila Activity Monitoring (DAM) System, recording activity from individual flies maintained in sealed tubes placed in activity monitors. The dSERT mutants demonstrated increased sleep durations and likelihood of sleeping, as well as decreased odds of waking. These behaviors were partially rescued in heterozygous flies. Genetic rescue experiments of the dSERT gene using the Gal4-UAS system were performed to confirm whether phenotypic differences in behavior were linked exclusively to the SERT allele. This work provides information critical for understanding the effects of increased extracellular serotonin and the mechanism of action for antidepressant drugs, which to date remains unknown.

Spinal cord injury (SCI) has two prominent stages. Primary injury is the beginning destruction that results in cell death and the demyelination of neurons. A secondary injury that is addressed prominently involves chronic inflammation and the formation of a glial scar. The injury also degrades the extracellular matrix of the spinal cord which is concentrated with high molecular weight hyaluronic acid (HA). As a result, the high molecular weight HA is degraded into low molecular weight HA which results in an imbalance between low molecular weight HA and high molecular weight HA. As a result, low molecular weight HA is responsible for initiating the antiinflammatory response while high molecular weight HA is associated with a proinflammatory response. The purpose of this experiment is to be able to analyze how varying the molecular weights of the HA affect the secretome of macrophages, one of the most important cell lines in the immune response. By analyzing the secretome of macrophages with varying molecular weights of HA we can gain a better understanding of the secondary response of SCI and how HA can modulate better healing of spinal tissue.

According to the American Psychiatric Association, 1 in 11 people will develop Post Traumatic Stress Disorder (PTSD) in their lifetime. Patients that suffer from PTSD experience many symptoms, including sleep disturbances and decreased adaptivity of the nervous system during stress, as measured by heart rate variability (HRV). Biologically, PTSD is characterized by an increase in signaling of noradrenaline from the locus coeruleus during REM sleep, which is more activated post-trauma. Since depotentiation, the weakening of the synapses of memories, can only occur during REM sleep in the absence of noradrenergic signaling, those with PTSD retain the full weight of emotions in their traumatic memories. Propranolol, a beta-adrenergic antagonist, has been used as a treatment for PTSD with an effectiveness rate of only 50%. We hypothesize that consideration of the timing of propranolol administration in relation to sleep will make the difference between effective and ineffective treatments. Administering propranolol after fear extinction (FE) learning but before REM sleep would show reduced freezing during FE recall, as extinction learning requires weakening of old fear memory associations. In addition, we expect propranolol-treated rats to show increased HRV, reflecting better adaptability. Therefore, we propose to investigate the cardiac R-R intervals during sleep-wake cycles in those receiving propranolol immediately after FE or after a 4 hour delay with saline controls. We hypothesize that rats that undergo immediate propranolol injection will have higher HRV. This study would provide increased understanding of post-stress autonomic system regulation and insight into effective ways to reverse the symptoms of PTSD.

Children diagnosed with autism spectrum disorder (ASD) that regress in previously attained skills show more significant deficits in social communication and are more likely to have moderate to severe intellectual disability relative to children with ASD without a regression (Ozonoff & Iosif, 2019). As early as 12 months of age, peak alpha frequency (PAF) differences have been observed in children who are later diagnosed with ASD (Dickinson et al., 2018). We examined changes in early developmental abilities from 12 to 18 months of age in infants with low- and high-risk for ASD and the potential role of differences in PAF in explaining these changes. We measured peak alpha band frequency (6-12 Hz) brain activity using EEG under a task-free condition at 6, 9, and 12 months. Developmental abilities were assessed using the Mullen Scales of Early Learning at 12 and 18 months. Diagnostic outcome was determined at 36 months, with children placed preliminary results showed that, as expected, gross and fine motor, receptive and expressive language, and visual receptive skills increased between 12 and 18 months, with outcome group differences observed in all areas except gross motor. However, the degree of change over time for receptive and expressive language, and visual receptive skills differed by group. Additionally, PAF differed by outcome group across all areas measured at 9 and 12 months. Next, we will examine the relationship between PAF in the first year of life and change in developmental abilities in the second year within outcome groups.