4.5 Article

Developmental PCB Exposure Disrupts Synaptic Transmission and Connectivity in the Rat Auditory Cortex, Independent of Its Effects on Peripheral Hearing Threshold

Journal

ENEURO
Volume 8, Issue 1, Pages -

Publisher

SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0321-20.2021

Keywords

auditory cortex; laser photostimulation; patch-clamp; PCB; toxin; uncaging

Categories

Funding

  1. National Institute of Environmental Health Sciences [NIEHS-R01 ES015687, NIEHS-T32 ES007326]
  2. Beckman Institute Postdoctoral Fellowship
  3. University of Illinois Research Board

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Early developmental exposure to PCBs leads to long-lasting changes in both inhibitory and excitatory neurotransmission in the auditory cortex, which are independent of peripheral hearing changes.
Polychlorinated biphenyls (PCBs) are enduring environmental toxicants and exposure is associated with neurodeve-lopmental deficits. The auditory system appears particularly sensitive, as previous work has shown that developmen-tal 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 whether the central ef-fects 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 (ABRs) were measured, and synaptic currents were recorded in slices from auditory cortex layer 2/3 neurons. Spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSCs) were more frequent in PCB-exposed rats compared with 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 re -sponse. 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 because of the direct impact of PCBs on the developing auditory cortex.

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