Effects of Moderate Prenatal Alcohol Exposure on NMDARs Expression and Functionality in Orbitofrontal Cortex Pyramidal Neurons
Alcohol consumption during pregnancy represents a major public health problem. Prenatal alcohol exposure (PAE) disrupts the Central Nervous System (CNS) development inducing long lasting behavioral and cognitive alterations collectively known as Fetal Alcohol Spectrum Disorders (FASDs). It is well established that alcohol affects different cellular targets, but the molecular mechanisms underlying these problems are not still understood. Our previous data reported a significant impairment in orbitofrontal cortex (OFC)-mediated reversal learning (Marquardt et al., 2014b), and an altered firing of OFC pyramidal neurons (Marquardt et al., 2020). Considering that N-Methyl-D-Aspartate receptors (NMDARs) are altered in rodent models after prenatal alcohol exposure (PAE), here we focused our attention on NMDARs expressed in OFC pyramidal neurons. Using a drinking-in-the dark voluntary paradigm combing with ex-vivo electrophysiology and western blotting, we characterized the functionality and expression of NMDARs in OFC pyramidal neurons coming from adult saccharine control (SAC) and PAE male and female mice. NMDA receptor-mediated evoked excitatory post- synaptic currents (NMDA-eEPSCs) were acquired at +40 mV and in the presence of the AMPAR antagonist NBQX (10 µM). GluN2A and GluN2B currents were isolated pharmacologically using PEAQX (1 µM) and Ro25-6981 (1 µM). The Linear Mixed Model analysis showed that PAE female mice have significantly larger NMDA –eEPSCs amplitude than PAE males. While, the current density is altered by PAE in male mice. The pharmacological isolation of GluN2B subunit mediated currents revealed that PAE treatment did not alter GluN2B function in both sex. Data confirmed by western blotting analysis, given that PAE did not modulate the protein level expression measured from synaptic fraction. These results demonstrate that the synaptic NMDARs function in OFC is modulated by PAE in sex specific manner, and at the same time give to scientific community an important tool for new pharmacological therapies.
Licheri, Valentina; Jayapriya Chandrasekaran; Clark W. Bird; Carlos F. Valenzuela; and Jonathan L. Brigman. "Effects of Moderate Prenatal Alcohol Exposure on NMDARs Expression and Functionality in Orbitofrontal Cortex Pyramidal Neurons." (2021). https://digitalrepository.unm.edu/hsc-bbhrd/40
Poster presented at the Brain & Behavioral Health Research Day 2021
Supported by National Institute on Alcohol Abuse and Alcoholism grants: 1R01AA025652-01, 1P50AA022534-01 & T32AA014127