The NKCC1 antagonist bumetanide mitigates interneuronopathy associated with ethanol exposure in utero.

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave.

Ethanol Exposure In Utero Disrupts Radial Migration and Pyramidal Cell Development in the Somatosensory Cortex.

Deficits in sensory processing in Fetal Alcohol Spectrum Disorders (FASD) implicate dysfunction in the somatosensory cortex. However, the effects of prenatal ethanol exposure on the development of this region await elucidation. Here, we used an established mouse model of FASD with binge-type ethanol exposure from embryonic day 13.

Persistent Interneuronopathy in the Prefrontal Cortex of Young Adult Offspring Exposed to Ethanol In Utero.

Unlabelled: 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.

Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood.

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior.

Ethanol consumption during early pregnancy alters the disposition of tangentially migrating GABAergic interneurons in the fetal cortex.

Consumption of alcohol (ethanol) during pregnancy can lead to developmental defects in the offspring, the most devastating being the constellation of symptoms collectively referred to as fetal alcohol syndrome (FAS). In the brain, a hallmark of FAS is abnormal cerebral cortical morphology consistent with insult during corticogenesis. Here, we report that exposure to a relatively low level of ethanol in utero (average maternal and fetal blood alcohol level of 25 mg/dl) promotes premature tangential migration into the cortical anlage of primordial GABAergic interneurons, including those originating in the medial ganglionic eminence (MGE).

Cajal-Retzius cells switch from expressing gamma-less to gamma-containing GABA receptors during corticogenesis.

Cajal-Retzius cells are implicated in regulating neuronal migration and lamination during corticogenesis. In rodents, Cajal-Retzius cells are transient, being prevalent in the marginal zone of the embryonic neocortex and declining over the first two postnatal weeks. While studies have examined in postnatal neocortex the properties of GABA(A) receptors in Cajal-Retzius cells, less is known about their disposition at embryonic stages.

Ambient GABA promotes cortical entry of tangentially migrating cells derived from the medial ganglionic eminence.

During corticogenesis, cells from the medial ganglionic eminence (MGE) migrate tangentially into the neocortical anlage. Here we report that gamma-aminobutyric acid (GABA), via GABAA receptors, regulates tangential migration. In embryonic telencephalic slices, bicuculline produced an outward current in migrating MGE-derived cells in the neocortex, suggesting the presence of and tonic activation by ambient GABA.

Brain-derived neurotrophic factor mitigates chronic ethanol-induced attenuation of gamma-aminobutyric acid responses in cultured cerebellar granule cells.

This study examined the effect of chronic exposure to ethanol and brain-derived neurotrophic factor (BDNF) on the responsiveness of cerebellar granule cells to gamma-aminobutyric acid (GABA). Cerebellar granule cell cultures were chronically exposed to ethanol (100 mM), BDNF (20 ng/ml), or the combination of ethanol and BDNF. Whole-cell current responses of granule cells to exogenously applied GABA were monitored following at least 5 days of chronic exposure.