Distribution of the alpha7 nicotinic acetylcholine receptor subunit in the developing chick cerebellum.

Previous studies of the nicotinic acetylcholine receptor (nAChR) subunits in adult mammalian and avian brains have demonstrated a spatially restricted distribution of these subunits; little, however, is known about the nAChR subunit developmental distribution. The present study demonstrated a transient pattern of distribution of the neuronal nAChR subunit, alpha7, in the developing chick cerebellum by using immunohistochemical techniques. This transient distribution may suggest a critical period for the development of the cholinergic system in the cerebellum.

Auditory event-related potentials in fetal alcohol syndrome and Down's syndrome children.

Abnormal or borderline electroencephalograms are commonly observed in cases of gross mental retardation. However, fewer studies have focused on the use of event-related responses to aid in the differential diagnosis of developmental cognitive disorders. Fetal alcohol syndrome (FAS) and Down syndrome represent the most common known causes of mental retardation in the Western world. Although Down syndrome is easily diagnosed with a chromosome assay, FAS can be more difficult to diagnose since the diagnostic features are more subjectively based. The present study is the first to characterize auditory event-related potentials (ERPs) in children with FAS and contrast them to subjects with Down syndrome and controls. A passive auditory "oddball-plus-noise" paradigm was utilized to elicit ERPs. Parietal P300 latencies in response to the noise-burst stimuli for the FAS children were significantly longer, as were the P300s from all cortical sites in Down syndrome subjects in response to the both the infrequent tone and noise-burst stimuli when compared with the controls. Frontal P300s in Down syndrome children were significantly larger in amplitude compared to the controls and FAS children in response to the infrequent tone. A discriminant function analysis also revealed that these children could be correctly classified as being either Down syndrome, FAS, or normal controls using measures of latency and amplitude of the P300. These data suggest that an evaluation of ERP characteristics may provide a better understanding of the differences between FAS and Down syndrome children, and prove to be an aid in the early identification of children with FAS. These results demonstrate neurophysiological differences between FAS and Down syndrome, and suggest that P300 amplitude and latency data collected from a passive ERP task may be helpful in the discrimination of developmental cognitive disorders.

EEG findings in fetal alcohol syndrome and Down syndrome children.

Results from previous studies evaluating the electroencephalograms (EEGs) of infants born to alcoholic mothers suggest that the neonatal EEG may be a sensitive measure of prenatal ethanol exposure. Few studies, however, have examined EEG records of adolescent children with fetal alcohol syndrome (FAS). The present study investigated the resting EEG recordings of 18 matched triads of FAS, Down syndrome, and normal control subjects. Significant reductions in mean power of the alpha frequencies (7.5-12 Hz) were seen for both clinical groups, however, each syndrome appeared to have distinct EEG spectral distributions. Down syndrome children overall had diffuse EEG slowing while the EEG records of the FAS children showed reduced power, particularly in the alpha frequencies in the absence of significant slow activity. In the Down syndrome children, significant decreases in alpha power was seen in posterior cortical regions, whereas FAS children were more affected in the left hemisphere. This study suggests that certain EEG variables may be helpful in characterizing the neurophysiology of FAS.

Effects of artificial rearing on electrophysiology and behavior in adult rats.

Maternal separation during crucial periods of development can lead to both physiological and behavioral sequelae. However, the exact consequences of maternal separation are paradigm dependent. The present study utilized complete artificial rearing (AR) to evaluate the effects of maternal separation on behavioral and electrophysiological functioning. In this procedure thermoregulation and weight gain progress are normal, but pups are deprived of any maternal influence from postnatal day 4 to 12. Artificial rearing was found to have no effect on EEG as assessed using spectral analyses. However, the N1 component of the auditory event-related potential (ERP) in artificially reared rats was significantly delayed. Artificial rearing had no effect on overall locomotor activity, but artificially reared rats were more behaviorally inhibited than suckled controls in the open field. This study suggests that artificial rearing or chronic maternal separation (24 h/day from PN4 to PN12), while not producing gross behavioral effects, can produce selective enduring alterations in neurosensory responses.

Effects of neurotensin on EEG and event-related potentials in the rat.

Neurotensin has neuromodulatory actions on multiple brain functions including motor, sensory and limbic processes. However, little is known about how neurotensin affects general arousal and/or attention states. The present study evaluated the effects of neurotensin on spontaneous brain activity as well as auditory evoked responses using electrophysiological measures. Electroencephalographic and event-related potential recordings were obtained in awake animals following intracerebroventricular administration of neurotensin (1.0, 10.0 and 30.0 micrograms). Twenty rats were implanted with recording electrodes in the frontal cortex, dorsal hippocampus, amygdala and nucleus accumbens. Neurotensin was found to produce a dose-related effect on behavior and electrophysiological measures. Lower doses (10 micrograms) produced no obvious behavioral changes, but significantly reduced EEG power in the lower frequency ranges (2-6 Hz) in the frontal cortex, the anterior amygdaloid complex and the nucleus accumbens. At higher doses (30 micrograms), rats appeared behaviorally inactivated, and EEG power was reduced in all structures in both the lower frequency ranges (2-6 Hz) and the higher frequency ranges (8-32 Hz). Auditory processing, as assessed by event-related potentials, was affected most significantly in amygdala and dorsal hippocampus. In the amygdala, the amplitude of the P3 component of the auditory event-related potential was increased significantly by doses of 10.0 and 30.0 micrograms. In the dorsal hippocampus, the amplitude and the area of the N1 component was increased dose dependently and significance was reached at the 30 micrograms dose. These electrophysiological findings indicate that neurotensin does not reduce the arousal level of the animals and in fact may enhance neurosensory processing in limbic areas through increased arousal and/or enhanced stimulus evaluation.

[Cryptorchism: basic concepts and hormonal therapy]. / Criptorquismo: conceitos básicos e tratamento hormonal.

The authors analyze the clinical results of 368 cryptorchid testis that received intramuscular human chorionic gonadotropin (HCG), at the dose of 50 U/kg once a week for 6 weeks. The patients with inguinal anatomical abnormalities or only with subtle retractility were excluded. There was a correlation among the testicle position, the cryptorchism side, the patient's age at the time of the therapy and the results obtained. We observed (i) a delay on child referral; (ii) concurrence of cryptorchism and systemic diseases, most of them with genetical origin; (iii) better results was obtained in children with retractile testis, older than 4 years old and with bilateral cryptorchism. The efficacy of second hormonal treatment was only present in retractile testis that showed partial response to the first hormonal therapy. It is argued that, although the treatment of children under 2 is less effective, the possible prevention of testicular lesions for this early intervention justify the hormonal therapy between 6 and 9 months of life.

Long-latency event-related potentials in rats: effects of task and stimulus parameters.

Animal models of event-related potentials have recently been developed in rats in order to gain further understanding of the psychobiological variables which underlie these waveforms. In the present study, unanesthetized male Wistar rats, chronically implanted with electrodes, were utilized in order to: (i) compare event-related potentials recorded following the presentation of passively presented auditory stimuli from different neocortical, hippocampal and perihippocampal sites; (ii) test the effects of changes in stimulus probability and loudness on event-related potentials recorded from those sites; and (iii) record event-related potentials from rats who were actively performing in a tone discrimination task. The results of these studies showed that in all electrode sites (frontal cortex, parietal cortex, entorhinal cortex, hippocampus) a series of large amplitude potentials in the 10-200 ms latency range could be recorded in response to passively presented stimuli. Late positive potentials in the 300-400 ms range were only identified in recordings from the posterior cortex, entorhinal area, and dorsal hippocampus. Some of these late positive components were also found to be sensitive to changes in stimulus probability. A similar series of waves were detected in a paradigm where rats were required to actively discriminate between two tones; however, the morphologies of the waveforms were found to be more distinct. These studies suggest that rats may be good subjects for the exploration of the neural origins of event-related potentials. These studies demonstrate that rats performing in an auditory discrimination task can generate electrophysiological potentials which are time locked to the onset of a "cognitively relevant" stimulus (event-related potentials). These potentials can be recorded in limbic (hippocampus and amygdala) and cortical (parietal cortex) brain sites. The event-related potentials recorded in rats respond to changes in stimulus parameters in a similar fashion to those previously described in monkeys and human subjects. The identification of a rat model of event-related potentials provides an opportunity to further explore the neural origins of event-related potentials, to estimate the role of genetics in determining individual variation in waveforms, as well as to provide electrophysiological assays of the effects of various drugs on neurosensory and cognitive processing.

A decrease in the size of the basal ganglia following prenatal alcohol exposure: a preliminary report.

Prenatal alcohol exposure is known to cause damage to the central nervous system. This study sought to further elucidate the structural brain damage that occurs following prenatal alcohol exposure in both children and rats. Two children with histories of maternal alcohol abuse but who did not qualify for a diagnosis of Fetal Alcohol Syndrome (FAS), based on established criteria, underwent magnetic resonance imaging. Reduced volumes were found for the cerebrum and cerebellum. In addition, the proportional volume of the basal ganglia was reduced, although the proportional volumes of cortical and subcortical fluid, cortical gray matter, limbic and nonlimbic cortex, and diencephalic structures were unaffected. These findings are compared with our recent MRI findings in two cases of FAS. In addition, the caudate-putamen and ventricular areas were assessed in rats exposed to alcohol prenatally. Whereas the overall brain section area was not reduced in size, the area of the caudate-putamen was reduced and that of the ventricles was enlarged.

The effects of acute cocaine administration on auditory event-related potentials in rats.

Cocaine administration has been shown to affect several sites in the limbic forebrain. The nucleus accumbens has been implicated as an important site for the reinforcing aspects of this drug whereas, the amygdala and hippocampus may be more involved in drug conditioning and/or drug induced changes in the perception of stimuli. In the present study, auditory event-related potentials (ERPs) were utilized to explore the effects of cocaine on sensory processing in several limbic sites. Eleven adult male Wistar rats were stereotaxically implanted with electrodes aimed at the dentate gyrus, dorsal hippocampus (CA1-CA2), amygdala, and nucleus accumbens. The rats received intraperitoneal injections of either saline, 2.5, 5.0, 10.0 or 20 mg/kg of cocaine. The ERPs were recorded in response to an auditory 'oddball' paradigm consisting of frequently and infrequently presented tones. Cocaine was found to produce a dose dependent decrease in the variance of the amplitude of several ERP components in the amygdala and the hippocampal formation but not in the nucleus accumbens. Cocaine also produced a decrease in the latency of the N1 component in the amygdala. No significant changes were observed in the amplitude of the ERP components following any of the cocaine doses studied, suggesting that cocaine may not increase the salience of auditory stimuli in these structures. The observed reduction in the variance of the ERPs may suggest an increased focussing of the animals' attention to the auditory stimuli. These studies also suggest that the sensory/cognitive aspects involved in cocaine's actions, as quantified by ERPs, may primarily involve the hippocampal formation and the amygdala, but not the nucleus accumbens.

Electrophysiological and behavioral findings in rats prenatally exposed to alcohol.

Clinical studies have shown that behavioral and electrophysiological abnormalities occur in some human infants born to alcoholic mothers. The present study used rats to evaluate the effects of prenatal ethanol exposure on locomotor behavior and two paradigms for the generation of auditory event-related potentials (ERPs). Pregnant rats were fed liquid diets, one group received alcohol and the other was a nutritional control. The offspring were allowed to mature prior to the electrophysiological and behavioral testing. Prenatal alcohol exposed rats showed significantly more locomotor behavior in the first 4 hours of their activity cycle than nonethanol exposed rats, although not over a subsequent 8-hour period. Evaluation of the electrophysiological data revealed that the prenatal alcohol exposed group had significantly longer latencies of their P1 and N1 ERP components, in the hippocampus, than the control group. These results support anatomical data suggesting that the hippocampus may be an important area in which to direct further study of what brain mechanisms may be altered by prenatal ethanol exposure in the rat.

Effects of gender and social isolation on electroencephalogram and neuroendocrine parameters in rats.

Social separation/isolation from either maternal or peer influence can induce a biobehavioral response in rodents and nonhuman primates seeming to mimic certain aspects of human psychopathology. To further explore this paradigm, the effects of 6 weeks of social isolation on electroencephalographic (EEG) recordings and hypothalamic-pituitary-adrenal (HPA) functioning were studied in male and female adult rats. Gender differences were observed in EEG and HPA axis functioning in these rats. Female rats, overall, were found to have higher levels of EEG slow-wave activity over the entire recording period, suggesting more intense levels of slow-wave sleep in those animals. Female rats were also observed to have overall higher plasma corticosterone concentrations and a lower anterior pituitary corticotropin-releasing factor (CRF) receptor density compared with male rats. The male rats, however, showed greater changes in response to social isolation than female rats. EEG power was increased as a result of social isolation in the male animals during the first 30-100 min of the recording. Reductions in the number of CRF receptors were also observed in the brains of the socially isolated rats in several cortical areas; however, again this effect was more prominent in the male animals. These studies suggest that gender is an important variable in determining the biobehavioral response to social isolation.

Effects of chronic corticosterone treatment on electrophysiological and behavioral measures in the rat.

The electrophysiological and behavioral effects of daily oral exposure to a corticosterone or vehicle solution was evaluated in 20 male Wistar rats over a 10-wk period. Evaluation of the rats' behavior in an open field apparatus, as well as in automated locomotor cages, revealed no significant differences between steroid-treated and control animals following 5-6 wk of exposure. No differences in mean EEG power, as estimated by spectral analysis of cortical and dorsal hippocampal recordings, were observed between the two groups following 8 wk of exposure. However, some increases in EEG "stability" were noted in the corticosterone-treated rats. At 9 wk, responses to auditory stimuli, as assessed by evoked responses, in cortex and dorsal hippocampus were also found to be unaltered by corticosterone exposure. These studies suggest that exposure to daily oral corticosterone, in the doses used, over a period of 2-3 mo is not associated with gross electrophysiological or spontaneous behavioral effects in the brain areas assessed.

Effects of dizocilpine (MK-801) and ethanol on the EEG and event-related potentials (ERPS) in rats.

Recent neurophysiological data have suggested an interaction of ethanol (EtOH) with the glutamate-NMDA receptor complex. For instance, low levels of alcohol have been found to inhibit the ion current, activated by NMDA in in vitro preparations. The present study extends these paradigms in order to evaluate the electrophysiological effects of ethanol and the nonspecific NMDA receptor antagonist, dizocilpine (MK-801) in awake, conscious rats. Twenty Wistar rats were stereotaxically implanted with electrodes, aimed at dorsal hippocampus, amygdala, thalamus and frontal cortex. Rats received the following drugs: saline (s.c.), 0.01 and 0.1 mg/kg MK-801 (s.c.); EtOH, 0.75 g/kg (i.p.); 0.75 kg EtOH plus 0.01 mg/kg MK-801; 0.75 g/kg EtOH plus 0.10 mg/kg MK-801. Five minutes of EEG was collected and event-related potentials (ERPs) recorded in response to an auditory "oddball" paradigm. Spectral analysis revealed that MK-801 (0.1 m/kg) produced significant increases in low frequency EEG components, at all sites (1-6 Hz) and decreases in higher frequencies (16-32 Hz). Whereas ethanol (0.75 g/kg) produced decreases in power in all frequency bands. The combined administration of EtOH and MK-801 produced some antagonistic effects on the EEG in the low frequency range. Evaluation of ERPs revealed that MK-801 (0.1 mg/kg) produced significant decreases in amplitude of the N1 and P2 components in the cortex, decreases in the P1 and N2 in the thalamus and a profound decrease in the P3 components in hippocampus and amygdala. Ethanol was also found to produce decreases in the N1 component in cortex. The administration of MK-801 and ethanol together did not produce significant interactions on ERPs. These studies suggest that antagonism of the NMDA receptor by MK-801 may produce some effects similar to those of ethanol, however, their combined administration did not produce synergistic effects within these dose ranges.

Combined effects of ethanol and MK 801 on locomotor activity in the rat.

The present study examined the effects of ethanol (0.75 g/kg IP) alone and in combination with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK 801 (0.1 mg/kg SC) on the locomotor activity of rats. Sixteen rats were treated with vehicle plus saline, MK 801 plus saline, vehicle plus ethanol, and MK 801 plus ethanol. Locomotor activity was quantified for a period of 12 hours following drug administration. Ethanol was found to significantly decrease locomotor activity whereas MK 801 significantly increased locomotion during the first 2 hours postdrug. In addition, there was a significant additive interaction between ethanol and MK 801 during this time period. Two to four hours postdrug, MK 801 was observed to significantly decrease locomotion. Four to six hours postdrug, ethanol-treated rats had significantly increased locomotor activity whereas MK 801-treated rats displayed significantly decreased locomotion. No significant interaction was found between ethanol and MK 801 4 to 6 hours postdrug. No significant effects of any of the drugs on locomotor activity were observed from 6 to 12 hours postdrug. These results suggest that ethanol and MK 801 produce a pattern of effects on locomotor activity which depend on the time elapsed following drug administration.