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Chronic Gestational Exposure to Ethanol Leads to Enduring Aberrances in Cortical Form and Function in the Medial Prefrontal Cortex
Author(s) -
Skorput Alexander G. J.,
Yeh Hermes H.
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13107
Subject(s) - parvalbumin , gabaergic , neuroscience , neurogenesis , ganglionic eminence , prefrontal cortex , excitatory postsynaptic potential , inhibitory postsynaptic potential , biology , endocrinology , interneuron , medicine , cognition
Background Exposure to ethanol (EtOH) in utero alters the disposition of tangentially migrating GABA ergic interneurons in the fetal brain. The medial ganglionic eminence ( MGE ) gives rise to a large portion of cortical GABA ergic interneurons, including the parvalbumin‐expressing interneurons that shape and contribute to inhibitory/excitatory (I/E) balance of the intracortical circuit. Here, we investigated in the mouse medial prefrontal cortex (m PFC ) the hypothesis that low levels of maternal EtOH consumption from closure of the neural tube embryonic day (E) 9.5 until birth result in an enduring interneuronopathy. Methods Pregnant mice were subjected to a 2% w/w EtOH consumption regimen starting at neural tube closure and ending at parturition. Neurogenesis in the MGE was assessed by 5‐bromo‐2‐deoxyuridine (BrdU) immunofluorescence at E12.5. The count and distribution of parvalbumin‐expressing interneurons were determined in adult animals, and patch clamp electrophysiology was performed to determine GABA ergic function and I/E balance. Open‐field behavior in adult mice was assessed to determine whether the EtOH‐exposed cohort displayed a lasting alteration in exploratory behavior. Results In embryos exposed to EtOH in utero, we found increased BrdU labeling in the MGE , pointing to increased neurogenesis. Adult mice prenatally exposed to EtOH were hyperactive, and this was associated with an increase in parvalbumin‐expressing GABA ergic interneurons in the m PFC . In addition, prenatal EtOH exposure altered the balance between spontaneous inhibitory and excitatory synaptic input and attenuated GABA ergic tone in layer V m PFC pyramidal neurons in juvenile mice. Conclusions These findings underscore that altered migration of GABA ergic interneurons contributes to the EtOH‐induced aberration of cortical development and that these effects persist into adulthood as altered cortical form and function.