Biology subjects

Roberts, B. L.

Publications and source records attributed to Roberts, B. L..

5 recordsLinked to original sources

bioRxiv2026

Brief high-fat diet exposure temporally reshapes affective behavior and prefrontal cortex function

High-fat diet consumption is linked to a higher risk of obesity, diabetes, cardiometabolic diseases, psychiatric disorders, and cognitive dysfunction. Energy homeostasis and mood fluctuate throughout the 24-hour day, and perturbations in these rhythms have consequences for brain, body, and behavior. Our recent work demonstrates that layer 2/3 pyramidal neurons in the prelimbic prefrontal cortex (plPFC), a key region in affective behavior and cognitive function, undergo daily rhythms in their physiological function. In this study, we investigate how a one-week acute high-fat diet (aHFD) alters affective behavior and plPFC function. Further, we used time-of-day as a tool to determine how initiation of a HFD impacts the physiological properties of layer 2/3 plPFC pyramidal neurons in male and female mice. To explore these phenomena, we implemented the open-field test (OFT) and DeepLabCut to gain dynamic whole-body spatiotemporal resolution in our behavioral analysis. Next, we employed patch-clamp electrophysiology to determine how aHFD alters the intrinsic membrane properties and action potential dynamics of these neurons. Here we show that aHFD produces time-of-day dependent changes in exploratory behavior and physiology of plPFC pyramidal neurons, including altered intrinsic properties, firing profiles, and voltage-dependent membrane conductance in both sexes. These results lay the groundwork to explore the physiological mechanisms by which aHFD impacts plPFC function, affective behavior, and cognition. Overall, this study highlights the importance of understanding how diet impacts neural function before the onset of obesity.

neuroscience↗

bioRxiv2025

Perinatal circadian desynchronization disrupts sleep and prefrontal cortex function in adult offspring

Sleep and circadian (daily) rhythms impact nearly all aspects of physiology and are critical for optimal organismal function. Disruption of the clock can lead to significant metabolic disorders, neuropsychiatric illness, and cognitive dysfunction. Our lab has previously shown that environmental circadian desynchronization (ECD) in adults alters the anatomical structure and neurophysiological function of prefrontal cortex (PFC) neurons, PFC mediated behaviors, as well as sleep quality. As the PFC undergoes significant development in utero and early life, and maternal disturbances during this period can have significant long-term ramifications, we hypothesized that disrupting the circadian environment of dams during the perinatal period would alter sleep and PFC function in adult offspring. Using a mouse model of ECD we investigated how perinatal ECD (pECD) modulates sleep quality in adult offspring. We also determined how pECD impacts PFC neural function in adult offspring using ex vivo patch-clamp electrophysiology, exploring how pECD alters synaptic function and action potential dynamics. We found that male pECD mice trended toward increased total sleep during the inactive (light) period with shorter sleep bouts during the active (dark) period. pECD did not change sleep behavior in female mice. Independent of time of day, pECD altered post-synaptic dynamics of excitatory neurotransmitter release onto plPFC pyramidal neurons. There was also a loss of time-of-day effects on cell endogenous properties in male pECD mice. Thus, pECD clearly alters sleep behavior and PFC function in male mice. However, female mice appear protected against the effects of pECD in these measures. Together, these experiments form the foundation for future studies to understand the lifelong neurobehavioral impact of pECD.

neuroscience↗

bioRxiv2024

Acute and Chronic Neural and Glial Response to Mild Traumatic Brain Injury in the Hippocampus

Traumatic brain injury (TBI) is an established risk factor for developing neurodegenerative disease. However, how TBI leads from acute injury to chronic neurodegeneration is limited to post-mortem models. There is a lack of connections between in vitro and in vivo TBI models that can relate injury forces to both macroscale tissue damage and brain function at the cellular level. Needle-induced cavitation (NIC) is a technique that can produce small cavitation bubbles in soft tissues, which allows us to relate small strains and strain rates in living tissue to ensuing acute and chronic cell death, tissue damage, and tissue remodeling. Here, we applied NIC to mouse brain slices to create a new model of TBI with high spatial and temporal resolution. We specifically targeted the hippocampus, which is a brain region critical for learning and memory and an area in which injury causes cognitive pathologies in humans and rodent models. By combining NIC with patch-clamp electrophysiology, we demonstrate that NIC in the Cornu Ammonis (CA)3 region of the hippocampus dynamically alters synaptic release onto CA1 pyramidal neurons in a cannabinoid 1 receptor (CB1R)-dependent manner. Further, we show that NIC induces an increase in extracellular matrix proteins associated with neural repair that is mitigated by CB1R antagonism. Together, these data lay the groundwork for advanced approaches in understanding how TBI impacts neural function at the cellular level, and the development of treatments that promote neural repair in response to brain injury. SIGNIFICANCECurrent models of mild TBI (mTBI) cannot relate injury forces to both macroscale tissue damage and brain function at the cellular level. We combine a microscale injury model in ex vivo brain slices while simultaneously recording glutamatergic inputs onto CA1 hippocampal pyramidal neurons. Post-injury examination of chronic tissue regeneration by astrocytes allow us to connect acute neuronal signaling responses to chronic fibrosis after TBI. These studies provide a new tool for understanding the physiological and molecular responses to TBI and lay the groundwork for future experiments unraveling the synaptic mechanisms that mediate these responses seconds, minutes, and days following injury.

neuroscience↗

bioRxiv2022

Electrophysiological identification of daily rhythms in the prefrontal cortex

The prefrontal cortex (PFC) is heavily involved in cognitive and emotional processes, including working memory, cognition, stress responses, and fear associated behaviors. Many PFC-associated behaviors are time-of-day dependent, and disruption of daily rhythms negatively impacts these behavioral outputs, yet how the disruption of daily rhythms impacts the fundamental function of PFC neurons, and the mechanism(s) by which this occurs, remains unknown. Using a mouse model, we demonstrate that the activity and action potential dynamics of prelimbic PFC neurons are regulated by time-of-day in a sex specific manner. Further, we show that postsynaptic K+ channels play a central role in mediating these rhythms, suggesting an intrinsic gating mechanism mediating information throughput. Finally, we demonstrate that environmental circadian desynchronization alters the intrinsic functioning of these neurons in part by increasing sensitivity GIRK channel activation. These key discoveries demonstrate daily rhythms contribute to the mechanisms underlying the essential physiology of PFC circuits, and provide potential mechanisms by which circadian disruption may impact the fundamental properties of neurons. Significance StatementDisruption of circadian rhythms, such as shift work and jet lag, are associated with negative physiological and behavioral outcomes, including changes in affective state, cognitive function, learning and memory. The prefrontal cortex (PFC) plays a critical role in these functions, yet how daily rhythms and desynchronization of these rhythms impact the physiology of neurons in the PFC is unknown. Here we demonstrate that daily rhythms impact the physiological function of PFC neurons in a sex-dependent manner, and that environmental circadian desynchronization alters PFC function irrespective of time-of-day. These findings provide not only a physiological context to the neural and behavioral changes associated with circadian desynchronization, but also highlight the importance of considering the temporal dimension in studies of neural circuits.

neuroscience↗

bioRxiv2018

Loss of charge at solvent exposed Lys residues does not induce the aggregation of superoxide dismutase 1

Mutations in superoxide dismutase 1 (SOD1) associated with familial amyotrophic lateral sclerosis (fALS) induce the protein to misfold and aggregate. To date, missense mutations at more than 80 different amino acid positions have been associated with disease. How these mutations perturb native structure to heighten the propensity to misfold and aggregate is unclear. One potential mechanism that has been suggested is that when mutations occur at positions occupied by charged amino acids, then repulsive forces that would inhibit aberrant protein:protein interactions would be reduced. Mutations at twenty-one charged residues in SOD1 have been associated with fALS. Here, we examined whether loss of positively charged surface Lys residues would induce the misfolding and aggregation of SOD1. We randomly mutated four different Lys residues (K30, K36, K75, K91) in SOD1 and expressed these variants as fusion proteins with yellow fluorescent protein (YFP). We also assessed whether these mutations induced binding to a conformation-restricted SOD1 antibody, designated C4F6, which recognizes non-natively folded protein. Our findings indicate that SOD1 generally tolerates mutations at surface exposed lysine residues, and that loss of positive charge is insufficient to induce aggregation. Our findings may explain why mutations at these Lys residues have not been identified in ALS patients.

biochemistry↗