Repeated third trimester-equivalent ethanol exposure inhibits long-term potentiation in the hippocampal CA1 region of neonatal rats.
Developmental ethanol exposure damages the hippocampus, causing long-lasting learning and memory deficits. Synaptic plasticity mechanisms (e.g., long-term potentiation [LTP]) contribute to synapse formation and refinement during development. We recently showed that acute ethanol exposure inhibits glutamatergic synaptic transmission and N-methyl-d-aspartate receptor (NMDAR)-dependent LTP in the CA1 hippocampal region of postnatal day (P)7-9 rats. The objective of this study was to further characterize the effect of ethanol on LTP in the developing CA1 hippocampus during the third trimester equivalent. To more closely model human ethanol exposure during this period, rat pups were exposed to ethanol vapor (2 or 4.5 g/dL in air, serum ethanol concentrations=96.6-147.2 or 322-395.6 mg/dL) from P2-9 (4h/d). Brain slices were prepared immediately after the end of the 4-h exposure on P7-9 and extracellular electrophysiological recordings were performed 1-7h later under ethanol-free conditions to model early withdrawal. LTP was not different than group-matched controls in the 96.6-147.2mg/dL group; however, it was impaired in the 322-395.6 mg/dL group. Neither alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)/NMDAR function nor glutamate release were affected in the 322-395.6 mg/dL ethanol exposure group. These data suggest that repeated in vivo exposure to elevated ethanol doses during the third trimester-equivalent period impairs synaptic plasticity, which may alter maturation of hippocampal circuits and ultimately contribute to the long-lasting cognitive deficits associated with fetal alcohol spectrum disorders.
Puglia
Michael P
MP
Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, 87131, USA.
Valenzuela
C Fernando
CF
D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000633:toxicity*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D011247:Pregnancy; D051381:Rats
D002492:Central Nervous System Depressants; D000431:Ethanol