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bioRxiv · 10.1101/2020.07.28.224048

Developmental PCB exposure disrupts synaptic transmission and connectivity in the rat auditory cortex, independent of its effects on peripheral hearing threshold

Lee, C. M.·Sadowski, R. N.·Schantz, S. L.·Llano, D. A.
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Abstract

Polychlorinated biphenyls (PCBs) are enduring environmental toxicants and exposure is associated with neurodevelopmental deficits. The auditory system appears particularly sensitive, as previous work has shown that developmental PCB exposure causes both hearing loss and gross disruptions in the organization of the rat auditory cortex. However, the mechanisms underlying PCB-induced changes are not known, nor is it known if the central effects of PCBs are a consequence of peripheral hearing loss. Here, we study changes in both peripheral and central auditory function in rats with developmental PCB exposure using a combination of optical and electrophysiological approaches. Female rats were exposed to an environmental PCB mixture in utero and until weaning. At adulthood, auditory brainstem responses were measured, and synaptic currents were recorded in slices from auditory cortex layer 2/3 neurons. Spontaneous and miniature inhibitory postsynaptic currents (IPSCs) were more frequent in PCB-exposed rats compared to controls and the normal relationship between IPSC parameters and peripheral hearing was eliminated in PCB-exposed rats. No changes in spontaneous EPSCs were found. Conversely, when synaptic currents were evoked by laser photostimulation of caged-glutamate, PCB exposure did not affect evoked inhibitory transmission, but increased the total excitatory charge, the number and distance of sites that evoke a significant response. Together, these findings indicate that early developmental exposure to PCBs causes long-lasting changes in both inhibitory and excitatory neurotransmission in the auditory cortex that are independent of peripheral hearing changes, suggesting the effects are due to the direct impact of PCBs on the developing auditory cortex. Significance StatementThe mechanisms by which developmental exposure to polychlorinated biphenyls (PCBs) disrupt the central nervous system are not yet known. Here we show that developmental PCB exposure is associated with long-lasting dysregulation of both excitatory and inhibitory neurotransmission in the rodent brain. We further find that, unlike controls, synaptic parameters in the auditory cortex of PCB-exposed rats are independent of peripheral hearing changes. These data suggest that PCB-related changes in the auditory cortex are independent of their effects on the auditory periphery and that PCB exposure may disrupt the plastic mechanisms needed to restore normal processing in the auditory cortex after peripheral hearing loss.

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Lee, C. M., Sadowski, R. N., Schantz, S. L., Llano, D. A.. 2020-07-29. Developmental PCB exposure disrupts synaptic transmission and connectivity in the rat auditory cortex, independent of its effects on peripheral hearing threshold. https://doi.org/10.1101/2020.07.28.224048

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