Impact of adolescent intermittent ethanol exposure on interneurons and their surrounding perineuronal nets in adulthood.

BACKGROUND

Binge alcohol exposure during adolescence results in long-lasting alterations in the brain and behavior. For example, adolescent intermittent ethanol (AIE) exposure in rodents results in long-term loss of functional connectivity among prefrontal cortex (PFC) and striatal regions as well as a variety of neurochemical, molecular, and epigenetic alterations. Interneurons in the PFC and striatum play critical roles in behavioral flexibility and functional connectivity. For example, parvalbumin (PV) interneurons are known to contribute to neural synchrony and cholinergic interneurons contribute to strategy selection. Furthermore, extracellular perineuronal nets (PNNs) that surround some interneurons, particularly PV+ interneurons, further regulate cellular plasticity. The effect of AIE exposure on the expression of these markers within the PFC is not well understood.

METHODS

The present study tested the hypothesis that AIE exposure reduces the expression of PV+ and choline acetyltransferase (ChAT)+ interneurons in the adult PFC and striatum and increases the related expression of PNNs (marked by binding of Wisteria floribunda agglutinin lectin) in adulthood. Male rats were exposed to AIE (5 g/kg/day, 2-days-on/2-days-off, i.e., P25 to P54) or water (CON), and brain tissue was harvested in adulthood (>P80). Immunohistochemistry and co-immunofluorescence were used to assess the expression of ChAT, PV, and PNNs within the adult PFC and striatum following AIE exposure.

RESULTS

ChAT and PV interneuron densities in the striatum and PFC were unchanged after AIE exposure. However, PNN density in the PFC of AIE-exposed rats was greater than in CON rats. Moreover, significantly more PV neurons were surrounded by PNNs in AIE-exposed subjects than controls in both PFC subregions assessed: orbitofrontal cortex (CON = 34%; AIE = 40%) and medial PFC (CON = 10%; AIE = 14%).

CONCLUSIONS

These findings indicate that, following AIE exposure, PV interneuron expression in the adult PFC and striatum is unaltered, while PNNs surrounding these neurons are increased. This increase in PNNs may restrict the plasticity of the ensheathed neurons, thereby contributing to impaired microcircuitry in frontostriatal connectivity and related behavioral impairments.