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

Christopher M Lee,Daniel A Llano,Renee N Sadowski,Susan L Schantz

doi:10.1523/eneuro.0321-20.2021

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 whether 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 (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 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 because of the direct impact of PCBs on the developing auditory cortex.

Highlights

Polychlorinated biphenyls (PCBs) are a family of compounds originally manufactured for many applications, including dielectrics, hydraulic fluids, coolants, and lubricants
We recorded auditory brainstem responses (ABRs) to assess hearing thresholds during adulthood (110–518 d), and used a mixed-effects model to test the effect of PCB exposure on hearing threshold, independent of age and litter effects
Developmental PCB exposure induces long-lasting increases in spontaneous inhibitory tone and increases in excitatory connectivity in auditory cortex We found that developmental PCB exposure results in paradoxically increased Spontaneous IPSCs (sIPSCs) amplitude and frequency and increased miniature IPSCs (mIPSCs) frequency in layer 2/3 of the auditory cortex (Fig. 4A), while inducing peripheral hearing loss

Summary

Introduction

Polychlorinated biphenyls (PCBs) are a family of compounds originally manufactured for many applications, including dielectrics, hydraulic fluids, coolants, and lubricants. Humans and rodents exposed to PCBs experience auditory dysfunction, including higher sound detection thresholds (Goldey et al, 1995; Grandjean et al, 2001; Powers et al, 2006; Trnovec et al, 2008; Min et al, 2014; Li et al, 2015), loss of outer hair cells (Crofton et al, 2000), reduced otoacoustic emission amplitudes (Lasky et al, 2002; Powers et al, 2006; Trnovec et al, 2008), and increased susceptibility to and severity of audiogenic seizures (Poon et al, 2015; Bandara et al, 2016). It is unclear to what degree these changes are because of direct actions of PCBs in the brain, or whether these changes are secondary effects of peripheral hearing loss

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Results

Conclusion