Model Of Fetal Alcohol Syndrome Research Articles

Critical periods for the effects of alcohol exposure on brain weight, body weight, activity and investigation

Using an animal model of fetal alcohol syndrome — which equates peak blood alcohol concentrations across different developmental periods — critical periods for the effect of alcohol on brain weight, activity and investigative behavior were examined. The periods of alcohol exposure were from gestational day (GD) 1 through 10, GD 11 through 22, postnatal day (PD) 2 through 10, or all three periods combined. The critical period of alcohol exposure for an increase in activity in juveniles was GD 11 through 22. This pattern was not seen in the same animals in adulthood; instead, increases in both activity and investigation were seen in animals exposed from PD 2 through 10 and not seen in animals exposed during all three periods combined. Brain weight was reduced by alcohol exposure from GD 11 through 22, PD 2 through 10 and all three periods combined. The period from PD 2 through 10 was the only period when the brain weight to body weight ratio was reduced. In conclusion, exposure to alcohol during the periods in the latter half of gestation or early postnatal period seem to have the most deleterious effects on the brain, activity and investigation in the rat. In addition, the effects of alcohol exposure over both the prenatal and postnatal period cannot be easily predicted from the effects of shorter periods of exposure.

In utero ethanol exposure decreases rapid eye movement sleep in female Sprague–Dawley rat offspring

There is substantial evidence to suggest that ethanol exposure during vulnerable periods of prenatal somatic growth results in a number of morphological abnormalities and cognitive deficits in offspring. Amongst the characteristics exhibited by affected individuals are abnormal sleeping patterns, particularly abnormal rapid eye movement (REM) sleep. To better understand how prenatal ethanol exposure specifically affects sleeping patterns in offspring, an animal model of fetal alcohol syndrome was investigated using the Sprague–Dawley rat. Our study demonstrated that the amount of time spent in REM sleep was reduced in female, but not male rats, which were exposed to ethanol in utero as compared to male and female saline controls. Similarly, % REM sleep for female saline control rats was almost twice that of females exposed to ethanol (11.9 vs. 6.9%). By contrast, ethanol treated and control saline males did not differ on the % REM measure (11.5 vs. 10.4%), nor did they differ from the female saline controls. No differences were observed between males and females or treatment groups in terms of time spent in either slow wave sleep or wakefulness.

Alterations in hippocampal and hypothalamic monoaminergic neurotransmitter systems after alcohol exposure during all three trimester equivalents in adult rats.

Animal models of Fetal Alcohol Syndrome (FAS) often rely on exposing the developing organism to alcohol during either the prenatal or postnatal period only. Very few studies have examined brain changes resulting from alcohol exposure during both the prenatal and postnatal period, a period which is equivalent to all three trimesters in humans. In this study, we examined the effects of alcohol exposure during this prolonged period of neural development on hippocampal and hypothalamic neurotransmitters in the rat. Pregnant dams were intubated with alcohol from gestational day (GD) 1 to GD 22 and then their pups were intubated with alcohol from postnatal day (PD) 2 to PD 10. Alcohol-exposed rats of both sexes exhibited increased hippocampal noradrenaline (NE) concentration compared to intubated and nontreated control animals. Within the hypothalamus, alcohol-exposed females but not males exhibited increased NE concentration. Hypothalamic serotonin (5-HT) concentration was reduced in both alcohol-exposed and intubated-control rats compared to nontreated controls. The results suggest that both the hippocampal and hypothalamic NE systems are especially vulnerable to alcohol insult that occurs during a period of neural development that corresponds to the full human prenatal period. alcohol syndrome, hippocampus, hypothalamus,

Vitamin E and β-carotene protect against ethanol combined with ischemia in an embryonic rat hippocampal culture model of fetal alcohol syndrome

Neurodevelopmental damage can occur as a result of in utero exposure to alcohol. Oxidative stress processes are one of many proposed mechanisms thought to contribute to nervous system dysfunction characterized in fetal alcohol syndrome (FAS). Therefore, this study examined neuroprotective effects of antioxidant supplementation during ethanol (EtOH) treatment (0, 200, 400, 800 or 1600 mg/dl) combined with concomitants of EtOH exposure: acute (2-h) ischemia (aISCH) and chronic (16-h) hypoglycemia (cHG). The antioxidants vitamin E and β-carotene protected embryonic hippocampal cultures against 0–1600 mg/dl EtOH/aISCH/cHG treatments. In addition, neuronal viability, as measured by MTT ((3,4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; 5 mg/ml)), was equal to untreated cultures when supplemented with vitamin E or β-carotene at 0–800 mg/dl or 0–200 mg/dl EtOH/aISCH/cHG, respectively. These in vitro studies mirror potential in utero ethanol-exposed CNS conditions and may lead to therapeutic strategies targeted at attenuating neurodevelopmental FAS-related deficits.

Effects ofin UteroAlcohol Exposure on B Cell Development in Neonatal Spleen and Bone Marrow

The effects ofin uteroalcohol exposure on neonatal lymphopoiesis were examined in a murine model of fetal alcohol syndrome. At birth, both immature and mature B cells were decreased in the spleens of neonatal animals and these subpopulations of B cells did not recover to normal levels until 3–4 weeks of life. Pre-B cells and total B cells were decreased as well in the bone marrow of ethanol-exposed animals. By 3–4 weeks of life, the number of B cells in the bone marrow recovered to normal levels, but the pre-B cells remained below normal levels through 5 weeks of age. Furthermore, a recently described early B cell progenitor was reduced in frequency in ethanol-exposed neonates. Together, these data suggest thatin uteroexposure to ethanol can result in abnormalities in B cell development that may initiate at an early stage of B cell development.

Defective Intracellular Processing of Lactase‐Phlorizin Hydrolase Protein in Rats Prenatally Exposed to Ethanol

We have previously shown that fetal exposure to ethanol in rats produces both structural and biochemical abnormalities in absorptive enterocytes. Among the indicators of injury are derangements in the expression of lactase-phlorizin hydrolase (LPH), which is an essential enzyme for the assimilation of milk. In an animal model of fetal alcohol syndrome, unsuckled newborn rats prenatally exposed to maternal ethanol revealed a 10- to 15-fold increase in the number of LPH mRNA molecules per absorptive enterocyte, compared with controls (Estrada et al., Alcohol. Clin. Exp. Res. 20:1662-1668, 1996). However, lactase activity per cell was similar in both groups. The aim of this study was to characterize the effect of prenatal exposure to ethanol on the processing of LPH mRNA and protein. RNase protection assays using 3'- and 5'-directed antisense RNA probes revealed that the LPH mRNA from ethanol-exposed pups is full length. However, metabolic labeling, followed by immunoprecipitation using an anti-LPH monoclonal antibody, demonstrated a significant alteration in LPH protein processing. Intestinal explants from 21-day ethanol-exposed fetuses that were chased 30 min after a [35S]methionine pulse showed greater amounts of newly synthesized LPH precursors (205 and 220 kDa) and low molecular weight degradation products than controls. However, despite the increases in LPH precursor, the amount of 130 kDa mature LPH was similar in ethanol-exposed and control explants. These data suggest an increase in intracellular degradation of LPH precursor in rats prenatally exposed to ethanol, which occurs before its insertion into the microvillus membrane. Biosynthesis of LPH appears to be upregulated at the transcriptional level, which overcomes the degradation of LPH precursor during processing.

Ethanol‐Induced Neural Crest Apoptosis Is Coincident with Their Endogenous Death, But Is Mechanistically Distinct

The ability of both acute and chronic ethanol exposures to elicit cell death within specific embryonic and adult tissues is believed to partly underlie ethanol's pathogenicity; however, the mechanism underlying this cell death is unknown. This study partially characterized the mechanism of ethanol-induced neural crest cell death in a chick embryo model of fetal alcohol syndrome. In situ DNA end-labeling demonstrated this cell death was apoptotic and occurred at embryonic ethanol levels as low as 42 mM. Regardless of the initial exposure time, this apoptosis always appeared at a distinct developmental time point simultaneous with the normal deletion of a cranial neural crest subset. This suggested that ethanol might act through aberrant activation of the endogenous death pathway; however, ethanol exposure failed to induce two components of this pathway, the homeotic transcription factor msx-2 and the growth factor bone morphogenetic protein 4. Both endogenous and ethanol-induced death were blocked by local application of an interleukin-1beta converting enzyme/CED-3 protease (caspase) inhibitor, showing that the two paths converge mechanistically and suggesting the potential to prevent this aspect of ethanol's teratogenicity. Ethanol exposure did not significantly alter cell proliferation within neural crest-populated regions, suggesting that susceptibility to ethanol-induced death did not involve exit from the cell cycle. Apoptotic deletion of cranial neural crest could partially explain the craniofacial deficits characteristic of the fetal alcohol syndrome.

The incidence of renal anomalies at full term in fetal rats is synergistically increased by estradiol (but not testosterone) supplementation on day 18 of alcoholic gestation

Background/Purpose: Fetal alcohol syndrome is characterized by facial dysmorphology, mental and growth retardation, and somatic anomalies including hydronephrosis. The authors sought to determine the influence of exogenous testosterone or estradiol on the incidence of hydronephrosis in a rodent model of fetal alcohol syndrome (FAS). Methods: Pregnant rats were fed a liquid diet containing 35% ethanol-derived calories from gestation day 6 through 15, with exogenous testosterone or estradiol supplementation on day 18. On day 20, fetal kidneys were examined for evidence of hydronephrosis, and fetal serum estradiol concentrations were determined by radioimmunoassay. Results: Maternal estrogen supplementation resulted in very high fetal serum estradiol levels that were not additionally increased by alcoholism. Despite this fact, the expression of renal malformations was highest in the alcoholic, estradiol-supplemented offspring. Additionally, the rate of renal malformations was significantly higher in the estrogen-supplemented alcoholic group than in the strictly estradiol animals, yet the fetal serum estradiol concentrations did not differ between the two groups. Conclusions: This suggests that ethanol may act synergistically with estradiol to increase the rate of renal anomalies including hydronephrosis. Such damage may persist via a suppression of normal testosterone-stimulated renal growth and development. FAS includes significant renal anomalies characterized by hydronephrosis in both animal models and affected children. Although the long-term functional sequelae of hydronephrosis and reflux are well known, the progression of renal disease in FAS children remains to be documented.

Fetal brain and liver phospholipid fatty acid composition in a guinea pig model of fetal alcohol syndrome: Effect of maternal supplementation with tuna oil

Chronic prenatal ethanol exposure may impair neurological development and function severely. We have shown previously that feeding ethanol to guinea pigs throughout pregnancy leads to decreased docosahexaenoic acid 22:6ω3) content in brain phospholipids, accompanied by impaired motor function comparable to some features of human fetal alcohol syndrome. We have tested the hypothesis that dietary supplementation of pregnant guinea pigs with 22:6ω3-enriched tuna oil may reduce the ethanol-induced deficit in 22:6ω3 accumulation into fetal brain. Guinea pigs (n = 5/ group) were maintained on chow diet either alone or supplemented with 6 gm ethanol/kg/day, ethanol, and tuna oil (0.5 gm/day; 130 mg 22:6ω3/day), or tuna oil alone both before and throughout pregnancy. Fetuses were assessed at term for brain and liver phospholipid fatty acid composition. Prenatal ethanol exposure significantly decreased fetal brain phosphatidylcholine (PC) and phosphatidylethanolamine (PE) 22:6ω3 contents and increased the PC PE ratio in fetal brain. Feeding both tuna oil and ethanol increased brain PC and PE 22:6ω3 content above control values, whereas the PC PE ratio was similar to control fetuses. Feeding tuna oil alone did not alter significantly the polyunsaturated content of fetal brain phospholipids. These feeding regimens induced markedly different changes to fetal liver phospholipid compositions compared with brain, which suggests that the effects of ethanol and/or tuna oil were tissue-specific. These results show that increased 22:6ω3 availability modified the effect of ethanol on developing fetal brain phospholipid composition. Such alterations to brain fatty acid content may potentially reduce some aspects of the harmful effects of maternal ethanol consumption on prenatal neurological development.

Effects of Prenatal Ethanol Exposure on Parvalbumin‐Expressing GABAergic Neurons in the Adult Rat Medial Septum

Exposure of human fetuses to ethanol often results in the fetal alcohol syndrome. Animal models of fetal alcohol syndrome have been developed and used to examine the consequences of prenatal ethanol exposure on the central nervous system. The objective of this study was to determine the long-term effects of prenatal ethanol exposure on parvalbumin-expressing (PA+) GABAergic neurons of the rat medial septum. Pregnant Long-Evans rats were maintained on 1 of 3 diets from gestational day 0 to 21: an ethanol-containing liquid diet in which ethanol accounted for 35% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, or a lab chow control diet. Offspring were killed on postnatal day 60, and their brains were prepared for parvalbumin immunocytochemistry. Female rats exposed to the ethanol-containing diet during gestation had 42% fewer PA+ neurons in the medial septum and reduced PA+ cell density when compared with female rats exposed to the sucrose diet. Ethanol females also had fewer PA+ neurons per unit volume than sucrose females. Male rats exposed to ethanol did not display a similar reduction in PA+ neurons or density. No effect of prenatal diet was found on the area or volume of the medial septum, nor were cell diameters affected. As such, prenatal exposure to ethanol seems to reduce permanently the number of PA+ neurons in the female rat medical septum without affecting area, volume, or neuronal size. Functional implications and possible relations to the fetal alcohol syndrome are discussed.

Studies of potential treatments for neurobehavioral dysfunction in animal models of fetal alcohol syndrome (FAS)

Studies of potential treatments for neurobehavioral dysfunction in animal models of fetal alcohol syndrome (FAS)

Chronic alcohol reduces calcium signaling elicited by glutamate receptor stimulation in developing cerebellar neurons

The effect of chronic alcohol (33 mM ethanol) on Ca 2+ signals elicited by glutamate receptor agonists (quisqualate and NMDA) was examined in developing cerebellar Purkinje and granule neurons in culture. The neurons were exposed to alcohol during the second week in culture, the main period of morphological and physiological development. The Ca 2+ signals were measured with fura-2 based microscopic video imaging. Chronic exposure to alcohol during development significantly reduced the peak amplitude of the Ca 2+ signals to quisqualate (1 μM; Quis) in both the somatic and dendrites regions of the Purkinje neurons. The dendrites region was affected to a greater extent than the somatic region. Granule neurons also showed a reduced somatic Ca 2+ signal to Quis (dendrites not measured) in the alcohol-treated cultures, indicating that the effect was not limited to Purkinje neurons. In addition to the effects on in the response to Quis, the peak amplitude of the Ca 2+ signals to NMDA (100 μM) was reduced by chronic alcohol exposure during development in both the cultured Purkinje and granule neurons. Resting Ca 2+ levels were not consistently affected by alcohol treatment in either neuronal type. These results indicate that Ca 2+ signaling linked to glutamate receptor activation is an important target of alcohol in the developing nervous system and could be a contributing factor in the altered CNS function and development observed in animal models of fetal alcohol syndrome.

Chronic alcohol reduces calcium signaling elicited by glutamate receptor stimulation in developing cerebellar neurons

The effect of chronic alcohol (33 mM ethanol) on Ca2+ signals elicited by glutamate receptor agonists (quisqualate and NMDA) was examined in developing cerebellar Purkinje and granule neurons in culture. The neurons were exposed to alcohol during the second week in culture, the main period of morphological and physiological development. The Ca2+ signals were measured with fura-2 based microscopic video imaging. Chronic exposure to alcohol during development significantly reduced the peak amplitude of the Ca2+ signals to quisqualate (1 μM; Quis) in both the somatic and dendrites regions of the Purkinje neurons. The dendrites region was affected to a greater extent than the somatic region. Granule neurons also showed a reduced somatic Ca2+ signal to Quis (dendrites not measured) in the alcohol-treated cultures, indicating that the effect was not limited to Purkinje neurons. In addition to the effects on in the response to Quis, the peak amplitude of the Ca2+ signals to NMDA (100 μM) was reduced by chronic alcohol exposure during development in both the cultured Purkinje and granule neurons. Resting Ca2+ levels were not consistently affected by alcohol treatment in either neuronal type. These results indicate that Ca2+ signaling linked to glutamate receptor activation is an important target of alcohol in the developing nervous system and could be a contributing factor in the altered CNS function and development observed in animal models of fetal alcohol syndrome.

Spatial locations gone awry: Object and spatial memory deficits in children with fetal alcohol syndrome

Hippocampus vulnerability following gestational alcohol exposure has been demonstrated neuroanatomically and behaviorally in animal models of fetal alcohol syndrome (FAS). There have been no similar demonstrations in humans. The Smith and Milner (1981) Memory for 16 Objects task has been used to explore the effects of right vs left temporal lobectomy with varying degrees of damage to the hippocampus. In the present experiment, this same task was administered to 15 children with FAS (mean age 10.03, S.D. = 2.33) and 15 control children (mean age 10.02, S.D. = 2.31). Similar to patients with right temporal lobectomies and a large excision to the hippocampus, children with FAS were able to perform immediate but not delayed object recall, had a general spatial memory deficit ( P < 0.05), and significantly distorted the spatial array ( P < 0.05). Although these results are consistent with an interpretation of hippocampal dysfunction, gestational alcohol exposure is known to result in a wide-ranging spectrum of neuropsychological deficits that vary in both extent and severity. Visuospatial deficits on the Beery test of Visuomotor Integration and Clock Drawing are suggestive of the other neural regions that may be involved in producing the behavioral deficits in children with FAS.

Effects of Prenatal Alcohol Exposure and Aging on Auditory Function in the Rat: Preliminary Results

This study investigated select aspects of peripheral and central auditory dysfunction, as well as the pathological effects of aging, In an animal model of fetal alcohol syndrome (FAS). Pregnant rats consumed liquid alcohol diets containing 0, 17.5, or 35% ethanol-derived calories, from gestation day 7 to parturition. A fourth group was untreated. Offspring of these mothers were tested for auditory and neurological function, using the auditory brainstem response at 6, 12, and 18 months of age. Some animals in the alcohol-exposed groups showed a peripheral auditory disorder in the form of congenital sensorineural hearing loss. This was correlated with punctate lesions and malformed stereocilia on the auditory sensory receptor cells of the inner ear. Alcohol-exposed animals also showed a central auditory processing disorder characterized by prolonged transmission of neural potentials along the brainstem portion of the auditory pathway. Animals in the highest dose group also showed an augmentation in the age-related deterioration of auditory acuity. Thus, increased peripheral and central auditory dysfunctions and pathological deterioration of auditory function in old age may be sequelae of FAS. Such morbidities have important implications for the long-term clinical assessment and management of FAS patients.

Abnormal development of the cerebellar vermis in children prenatally exposed to alcohol: size reduction in lobules I-V.

Abnormalities of the cerebellar vermis have been well documented in animal models of fetal alcohol syndrome. At this point, it is not known if the same brain region is affected in humans prenatally exposed to alcohol. In this study, the area of the cerebellar vermis was measured from brain magnetic resonance images of 9 children and young adults with prenatal alcohol exposure and 24 control subjects in the same age range. Six of the exposed children met standard criteria for fetal alcohol syndrome. The remaining three subjects had significant histories of prenatal exposure to alcohol, but did not have enough of the classic facial features for the diagnosis. For each subject with a suitable midsagittal section, three vermal areas were circumscribed: anterior vermis (vermal lobules I-V), posterior vermis (vermal lobules VI and VII), and the remaining vermal area (including lobules VIII-X). Statistical analyses revealed that the anterior region of the vermis was significantly smaller in subjects with prenatal alcohol exposure, whereas the posterior region and the remaining vermal area did not differ between groups. Previous findings from an animal model of neonatal alcohol exposure have documented Purkinje cell loss in vermal lobules I-V and IX-X, with notable sparing in lobules VI-VII. Thus, the results of both studies indicate similar patterns of abnormal brain development in the anterior vermal region, with apparent sparing in the posterior vermal region. Our findings, for the first time, suggest that regionally specific Purkinje cell death may also occur in humans prenatally exposed to alcohol.

Chronic prenatal ethanol exposure alters the normal ontogeny of choline acetyltransferase activity in the rat septohippocampal system.

In animal models of fetal alcohol syndrome (FAS), the hippocampus has been shown to be especially sensitive to the effects of prenatal ethanol exposure, exhibiting neuronal loss and alterations in neuritic process elaboration. We have characterized the influence of chronic prenatal ethanol treatment (CPET) on the postnatal expression of choline acetyltransferase (ChAT) in the hippocampus and the septal area that contains neurons that provide the primary cholinergic innervation to the hippocampus. On gestation days 1-22, pregnant rats were either fed an ethanol-containing liquid diet, pair-fed a calorically equivalent sucrose-containing diet, or given rat chow ad libitum. In Chow control animals, the ontogenetic progression of ChAT activity in the septal area and hippocampus was characterized by a significant period of upregulation during the 2nd and 3rd postnatal weeks, exhibiting and an approximate 5-fold increase (septal area) and 7-fold increase (hippocampus) by postnatal day 21 (P21). At P14, ethanol exposure reduced septal and hippocampal ChAT activity levels, compared with those of pair-fed offspring. ChAT activity reached control levels by P21 in ethanol-exposed pups, suggesting that the earlier decline in activity may reflect a delay in the ontogenetic upregulation. In addition, there was a trend toward increased septal and hippocampal ChAT activities at P1 and P7 in both liquid diet groups. This liquid diet-stimulated increase may mask the effects of ethanol on early postnatal ChAT expression in the septohippocampal system. The results suggest that prenatal ethanol exposure may influence factors that regulate the developmental expression of ChAT in the septohippocampal system.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of maternal ethanol consumption during pregnancy on the phospholipid molecular species composition of fetal guinea-pig brain, liver and plasma

The effect of maternal ethanol consumption during pregnancy upon accumulation of docosahexaenoic acid (22:6( n − 3)) into developing brain phospholipids was determined in a guinea-pig model of fetal alcohol syndrome. Feeding adult guinea-pigs 6 g/kg per day ethanol both before and throughout pregnancy was associated with decreased 22:6( n − 3) concentration in both fetal brain phosphatidylcholine (PC) and phosphatidylethanolamine (PE) at 40/68 days gestation and at term. Since adequate assimilation of 22:6( n − 3) into fetal brain is critical for optimal neuronal development, reduced accumulation of 22:6( n − 3) into phospholipids may be one important mechanism for ethanol-induced brain damage. Liver from ethanol-exposed fetuses contained significantly lower concentrations of both PC and PE 22:6( n − 3)-containing molecular species. However, there was no difference in plasma PC polyunsaturated fatty acid content in ethanol-exposed fetuses compared with controls. One possible explanation for impaired 22:6( n − 3) accumulation into ethanol-exposed fetal brain phospholipids may be the result of the action of inappropriate mechanisms which counteract ethanol-induced increased membrane fluidity by reducing the polyunsaturated fatty acid content of brain phospholipids.

Maternal ethanol ingestion effects on fetal rat brain vitamin A as a model for fetal alcohol syndrome.

Fetal embryo, head, and brain tissue from different gestational ages were analyzed for retinol content, nuclear retinoic acid receptor and cytosolic retinoic acid binding protein levels after maternal ethanol ingestion and compared with fetal levels in control diet pregnancies. Retinol levels in fetal embryo and brain of ethanol-ingesting pregnancies were 2- to 3-fold higher than fetal embryo and brain retinol of control pregnancies. Nuclear retinoic acid receptor was lower in 10-day embryo of ethanol pregnancies and apparently unaffected in fetal head and brain by maternal ethanol consumption at other days of gestation. In fetal head there was a significant overall ethanol effect on cytosolic retinoic acid binding protein, with increased levels in fetal tissue from ethanol-consuming pregnancies. These observations of altered embryo, fetal head, and fetal brain retinol and receptor protein levels support the hypothesis of a possible role of vitamin A in fetal alcohol syndrome.

Chronic exposure to alcohol during development alters the membrane properties of cerebellar Purkinje neurons in culture

The active and passive membrane properties of developing Purkinje neurons in control cultures and cultures chronically treated with 20 or 40 mM ethanol for 1 or 2 weeks were examined using whole-cell current-clamp techniques. The membrane properties were characterized by the features of the voltage responses evoked by intracellular current injection of a series of depolarizing and hyperpolarizing current pulses. Analysis of these responses and background spontaneous activity showed several differences between the control and ethanol-treated Purkinje neurons: (1) membrane input resistance was significantly larger in the ethanol-treated neurons; (2) the percentage of neurons exhibiting immature firing patterns was significantly higher in the ethanol-treated neurons; (3) the afterhyperpolarization following a current-evoked train of action potentials was significantly larger in the ethanol-treated neurons; (4) spontaneous activity (synaptic potentials and synaptically evoked spike events) was significantly reduced in neurons treated with 40 mM ethanol for 1 week; spontaneous activity in neurons treated with 20 mM ethanol for 1 or 2 weeks was similar to that observed in the control group. These differences indicate that ethanol exposure during development directly alters the physiological properties of this CNS neuronal type. These neuronal actions of ethanol may contribute to the behavioral deficits observed in animal models of fetal alcohol syndrome. Similar target sites of ethanol action are likely to be present in the human CNS neurons and may be involved in human fetal alcohol syndrome.