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We began analyzing https://www.jneurosci.org/content/35/31/10977, but it redirected us to https://www.jneurosci.org/content/35/31/10977. The analysis below is for the second page.

Title[redir]:
Persistent Interneuronopathy in the Prefrontal Cortex of Young Adult Offspring Exposed to Ethanol In Utero | Journal of Neuroscience
Description:
Gestational exposure to ethanol has been reported to alter the disposition of tangentially migrating GABAergic cortical interneurons, but much remains to be elucidated. Here we first established the migration of interneurons as a proximal target of ethanol by limiting ethanol exposure in utero to the gestational window when tangential migration is at its height. We then asked whether the aberrant tangential migration of GABAergic interneurons persisted as an enduring interneuronopathy in the medial prefrontal cortex (mPFC) later in the life of offspring prenatally exposed to ethanol. Time pregnant mice with Nkx2.1Cre/Ai14 embryos harboring tdTomato-fluorescent medial ganglionic eminence (MGE)-derived cortical GABAergic interneurons were subjected to a 3 day binge-type 5% w/w ethanol consumption regimen from embryonic day (E) 13.5–16.5, spanning the peak of corticopetal interneuron migration in the fetal brain. Our binge-type regimen increased the density of MGE-derived interneurons in the E16.5 mPFC. In young adult offspring exposed to ethanol in utero , this effect persisted as an increase in the number of mPFC layer V parvalbumin-immunopositive interneurons. Commensurately, patch-clamp recording in mPFC layer V pyramidal neurons uncovered enhanced GABA-mediated spontaneous and evoked synaptic transmission, shifting the inhibitory/excitatory balance toward favoring inhibition. Furthermore, young adult offspring exposed to the 3 day binge-type ethanol regimen exhibited impaired reversal learning in a modified Barnes maze, indicative of decreased PFC-dependent behavioral flexibility, and heightened locomotor activity in an open field arena. Our findings underscore that aberrant neuronal migration, inhibitory/excitatory imbalance, and thus interneuronopathy contribute to indelible abnormal cortical circuit form and function in fetal alcohol spectrum disorders. SIGNIFICANCE STATEMENT The significance of this study is twofold. First, we demonstrate that a time-delimited binge-type ethanol exposure in utero during early gestation alters corticopetal tangential migration of GABAergic interneurons in the fetal brain. Second, our study is the first to integrate neuroanatomical, electrophysiological, and behavioral evidence that this “interneuronopathy” persists in the young adult offspring and contributes to enduring changes in (1) the distribution of parvalbumin-expressing GABAergic cortical interneurons in the medial prefrontal cortex, (2) GABA-mediated synaptic transmission that resulted in an inhibitory/excitatory synaptic imbalance, and (3) behavioral flexibility. These findings alert women of child-bearing age that fetal alcohol spectrum disorders can be rooted very early in fetal brain development, and reinforce evidence-based counseling against binge drinking even at the earliest stages of pregnancy.

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🌟 Strong Traffic: 100k - 200k visitors per month


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Keywords {🔍}

ethanol, control, mpfc, interneurons, offspring, cortical, scholar, cells, utero, young, adult, gabaergic, exposure, migration, fig, ethanolexposed, pmidopenurlcrossrefpubmedgoogle, layer, pyramidal, synaptic, mice, recorded, neurons, etoh, red, mgederived, embryonic, alcohol, exposed, test, black, behavioral, cortex, unpaired, current, dots, figure, tangential, evoked, mouse, line, full, function, litters, textgoogle, day, brain, nkx, analysis, inhibitory,

Topics {✒️}

tdtomato-fluorescent mge-derived cells tdtomato-fluorescent cellular profiles harbors tdtomato-fluorescent nkx2 ai14 cre-reporter mouse vis-á-vis excitation mge-derived interneurons innervating stimulus-evoked synaptic response gaba-mediated synaptic transmission mge-derived gabaergic interneurons altering gaba-mediated neurotransmission ai14 cre-reporter mice cre recombination-based expression dapi-counterstained fluorescent image gestational stage-delimited paradigm 1cre/ai14 reporter line gaba-mediated synaptic events binge-type regimen increased vivo binge-type paradigm 1cre/ai14 mouse line gestational age-delimited exposure excitatory stimulus-evoked responses binge-type ethanol exposure mge-derived interneurons destined equivalent rostral-caudal levels counting tdtomato-fluorescent inter-event interval reinforce evidence-based counseling openurlcrossrefpubmedgoogle scholar ↵batista-brito differentially affected long-term pfc-dependent behavioral symptoms developmental cell-type switch pfc-dependent behavioral deficit halogen-illuminated epifluorescence images childbearing age—united states bicuculline-sensitive current showed achieve large-scale pacing alcohol-related birth defects patch-clamp recording pipette pfc-dependent executive function dartmouth-hitchcock medical center cortical zone-specific rois 1cre/ai14 mouse 1cre/ai14 embryos cnqx/apv-sensitive currents utero ethanol-induced enhancement ethanol-exposed cohorts led dapi-counterstained cross section ethanol-exposed mice committing inhibitory/excitatory synaptic imbalance main content log

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