Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction in mice.

Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild-type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a three-chamber social approach task, ultrasonic vocalization detection, elevated-plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic-like behaviors in offspring.

Low frequency oscillations in rat posterior parietal cortex are differentially activated by cues and distractors.

The posterior parietal cortex (PPC) is hypothesized to detect visual cues among competing distractors. Anatomical and neurophysiologic evidence indicates that the rat PPC is part of a network of brain areas involved in directed attention, specifically when new task parameters or conditions are introduced. Here, we test the hypothesis that changes in the local field potential (LFP) of the PPC of rats performing a sustained attention task reflect aspects of detection. Two event-related potentials were observed during detection: the P300 response and the contingent negative variation (CNV). Spectrogram analysis also indicated a detection-specific increase in alpha power in the retention interval of this task. This is consistent with observations from human studies, which indicate that tasks requiring a subject to withhold a response produced a pronounced synchronization of alpha rhythms during the delay, and desynchronization during retrieval. We also found cycles of alpha synchrony and desynchrony in response to a periodic distractor. These cycles were most pronounced in the initial trial block of the distractor when the false alarm rate was highest, and as task performance improved these cycles significantly diminished. This result suggests that alpha cycling in the PPC represent neural activity critical for learning to inhibit distractors. The occurrence of alpha synchronization and desynchronization to attention-demanding stimuli, in addition to the P300 and CNV responses observed during detection, is evidence that rat PPC is involved in sustained attention, particularly in the presence of distractors.

Ethanol-induced developmental neurodegeneration in secretin receptor-deficient mice.

Alcohol exposure during brain development induces neuronal cell death in the brain. Several neuroactive peptides have been shown to protect against alcohol-induced cell death. Secretin is a peptide hormone, and the secretin receptor is expressed in the gut and the brain. To explore a potential role of secretin signal against ethanol neurotoxicity during brain development, secretin receptor-deficient mice were exposed to ethanol on postnatal day 4. We identified significant ethanol-induced apoptosis in the external granular layer of the secretin receptor-deficient cerebellum and in the striatum after ethanol treatment. During the early postnatal period, there is a proliferation of granular cell progenitors that reside in the external granular layer. The results suggest that secretin signal plays a neuroprotective role of neuronal progenitor cells against the neurotoxicity of ethanol.

Theta reset produces optimal conditions for long-term potentiation.

Connections among theta rhythm, long-term potentiation (LTP) and memory in hippocampus are suggested by previous research, but definitive links are yet to be established. We investigated the hypothesis that resetting of local hippocampal theta to relevant stimuli in a working memory task produces optimal conditions for induction of LTP. The timings of the peak and trough of the first wave of reset theta were determined in initial sessions and used to time stimulation (4 pulses, 200 Hz) during subsequent performance. Stimulation on the peak of stimulus-reset theta produced LTP while stimulation on the trough did not. These results suggest that a memory-relevant stimulus produces a phase shift of ongoing theta rhythm that induces optimal conditions for the stimulus to undergo potentiation.