title: Ethanol inhibits long-term potentiation in hippocampal CA1 neurons, irrespective of lamina and stimulus strength, through neurosteroidogenesis.
abstract: Ethanol inhibits memory encoding and the induction of long-term potentiation (LTP) in CA1 neurons of the hippocampus. Hippocampal LTP at Schaffer collateral synapses onto CA1 pyramidal neurons has been widely studied as a cellular model of learning and memory, but there is striking heterogeneity in the underlying molecular mechanisms in distinct regions and in response to distinct stimuli. Basal and apical dendrites differ in terms of innervation, input specificity, and molecular mechanisms of LTP induction and maintenance, and different stimuli determine distinct molecular pathways of potentiation. However, lamina or stimulus-dependent effects of ethanol on LTP have not been investigated. Here, we tested the effect of acute application of 60 mM ethanol on LTP induction in distinct dendritic compartments (apical versus basal) of CA1 neurons, and in response to distinct stimulation paradigms (single versus repeated, spaced high frequency stimulation). We found that ethanol completely blocks LTP in apical dendrites, whereas it reduces the magnitude of LTP in basal dendrites. Acute ethanol treatment for just 15 min altered pre- and post-synaptic protein expression. Interestingly, ethanol increases the neurosteroid allopregnanolone, which causes ethanol-dependent inhibition of LTP, more prominently in apical dendrites, where ethanol has greater effects on LTP. This suggests that ethanol has general effects on fundamental properties of synaptic plasticity, but the magnitude of its effect on LTP differs depending on hippocampal sub-region and stimulus strength.
authors.affiliation: Trans-Synaptic Signaling Group, European Neuroscience Institute (ENI), Grisebachstrasse 5, 37077, Goettingen, Germany.
authors.forename: Binu
authors.initials: B
authors.lastname: Ramachandran
authors.forename: Saheeb
authors.initials: S
authors.lastname: Ahmed
authors.forename: Noman
authors.initials: N
authors.lastname: Zafar
authors.forename: Camin
authors.initials: C
authors.lastname: Dean
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017966:Pyramidal Cells / Q000187:drug effects*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: hippocampus; neurosteroid; synaptic plasticity; synaptic proteins