Biology subjects

McGlothan, J. L.

Publications and source records attributed to McGlothan, J. L..

3 recordsLinked to original sources

bioRxiv2020

Chronic lead exposure causes theta and gamma hypersynchrony in the hippocampus and disrupts sensorimotor gating

Chronic early-life lead (Pb2+) exposure contributes to an array of cognitive and behavioral dysfunctions, including impaired attention, memory, and intellectual abilities, in addition to increased social delinquency. Notably, Pb2+ exposure is an environmental risk factor for adult psychopathologies, including schizophrenia and epilepsy. Neurobiologically, Pb2+ is a potent N-methyl-D-aspartate receptor (NMDAR) antagonist, and exposure during early life elicits a cascade of cellular neurotoxic effects that alter neurodevelopmental trajectories. This includes reduced parvalbumin-expressing interneurons in the hippocampus (HC) and altered synaptic transmission. Little is known, however, about the impact of chronic Pb2+ exposure on HC network dynamics, which link cellular-molecular effects with cognitive-behavioral consequences. Here, we tested the impact of chronic Pb2+ exposure on the HC local field potential (LFP) in freely behaving rats. We found that Pb2+ exposure (1) caused a striking level of theta rhythmic hypersynchrony, (2) amplified fast gamma synchronization, (3) disrupted behavioral modifications of theta and fast gamma, and (4) exacerbated absence seizures appearing in the LFP as spike-wave discharges (SWDs) at theta frequencies. Each of these rhythmic changes in the HC network was related to exploratory movements in the open field. HC network alterations like these have also been linked to impaired prepulse inhibition of the acoustic startle reflex (PPI). Thus, next, we tested the effect of Pb2+ exposure on PPI. We found that adult males (PN50 and 120), but neither females nor juvenile males, showed reduced PPI, recapitulating sex dependencies on PPI disruptions in schizophrenics. Altogether, these results are consistent with the hypothesis that chronic early-life Pb2+ exposure causes dysfunction in the rhythmic network coordination of the HC, limiting processing, and helping to account for cognitive deficits.

neuroscience↗

bioRxiv2020

Chronic Developmental Lead Exposure increases μ-Opiate Receptor Levels in the Adolescent Rat Brain

Opioid use and abuse has reached epidemic proportion in the United States resulting in a significant numbers of deaths due to overdose. While environmental factors are implicated in opioid addiction, less is known about the role of exposure to environmental pollutants on the brain opioid system. Human and preclinical studies have suggested an association between childhood lead (Pb2+) intoxication and proclivity to substance abuse and delinquent behavior. Opioid receptors are involved in the biological effects of opioids and other drugs of abuse. In this study, we examine the effect of chronic developmental Pb2+ exposure on -opioid receptor (MOR) levels in the rat brain using [3H]-D-Ala2-MePhe4-Gly-ol5 enkephalin ([3H]-DAMGO) quantitative receptor autoradiography. Our results indicate that chronic developmental Pb2+ exposure increases the levels of [3H]-DAMGO specific binding to MOR in several limbic regions of the brain in male and female rats during the pre-adolescence (PN14) and early-adolescence (PN28) period. These changes were less pronounced in late-adolescence (PN50) and adult (PN120) animals. Our findings are important because the pre-adolescence and early adolescence period is a time in which there is higher engagement in reward and drug seeking behaviors in humans. In summary, we show that chronic exposure to Pb2+ an ubiquitous and well-known environmental contaminant and neurotoxicant, alters MOR levels in brain regions associated with addiction circuits in the adolescent period with important implications to opioid drug use and abuse.

pharmacology and toxicology↗

bioRxiv2019

'Awake delta' and theta-rhythmic hippocampal network modes during intermittent locomotor behaviors in the rat

Delta-frequency network activity is commonly associated with sleep or behavioral disengagement accompanied by a dearth of cortical spiking, but delta in awake behaving animals is not well understood. We show that hippocampal (HC) synchronization in the delta frequency band (1-4 Hz) is related to animals locomotor behavior using a detailed analysis of simultaneous head- and body-tracking data. In contrast to running-speed modulation of the theta rhythm (6-10 Hz, a critical mechanism in navigation models), we observed that strong delta synchronization occurred when animals were stationary or moving slowly and while theta and fast gamma (55-120 Hz) were weak. We next combined time-frequency decomposition of the local field potential with hierarchical clustering algorithms to categorize momentary estimations of the power spectral density (PSD) into putative modes of HC activity. Delta and theta power measures from these modes were notably orthogonal, and theta and delta coherences between HC recording sites were monotonically related to theta-delta ratios across modes. Next, we focused on bouts of precisely-defined running and stationary behavior. Extraction of delta and theta power density estimates for each instance of these bout types confirmed the orthogonality between frequency bands seen across modes. We found that delta-band and theta-band coherence within HC, and in a small sample, between HC and medial prefrontal cortex (mPFC), mirrored delta and theta components of the PSD. Delta-band synchronization often developed rapidly when animals paused briefly between runs, as well as appearing throughout longer stationary bouts. Taken together, our findings suggest that delta-dominated network modes (and corresponding mPFC-HC couplings) represent functionally-distinct circuit dynamics that are temporally and behaviorally interspersed amongst theta-dominated modes during navigation. As such these modes of mPFC-HC circuit dynamics could play a fundamental role in coordinating encoding and retrieval mechanisms or decision-making processes at a timescale that segments event sequences within behavioral episodes.

neuroscience↗