Neuropathological studies, using a variety of techniques, have reported a decrease in Purkinje cell (PC) density in the cerebellum in autism. We have used a systematic sampling technique that significantly reduces experimenter bias and variance to estimate PC densities in the postmortem brains of eight clinically well-documented individuals with autism, and eight age- and gender-matched controls. Four cerebellar regions were analyzed: a sensorimotor area comprised of hemispheric lobules IV–VI, crus I & II of the posterior lobe, and lobule X of the flocculonodular lobe. Overall PC density was thus estimated using data from all three cerebellar lobes and was found to be lower in the cases with autism as compared to controls, an effect that was most prominent in crus I and II (p<0.05). Lobule X demonstrated a trend towards lower PC density in only the males with autism (p = 0.05). Brain weight, a correlate of tissue volume, was found to significantly contribute to the lower lobule X PC density observed in males with autism, but not to the finding of lower PC density in crus I & II. Therefore, lower crus I & II PC density in autism is more likely due to a lower number of PCs. The PC density in lobule X was found to correlate with the ADI-R measure of the patient's use of social eye contact (R2 = −0.75, p = 0.012). These findings support the hypothesis that abnormal PC density may contribute to selected clinical features of the autism phenotype.

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There is considerable evidence that co-infection with the sexually transmitted pathogen Neisseria gonorrhoeae (Gc) can increase the likelihood of both transmitting and acquiring HIV-1 worldwide. However, less information is available on how host immune response to co-infection differs with immune response to HIV-1 infection alone. To evaluate HIV-1 burden effects on host response to co-infection with Gc, we performed gene-expression profiling of human PBMCs infected over a broad range of viral titers (HIV-1 series) and upon exposure to a single infectious dose of Gc (HIV-1/Gc series). The transcriptional profiles differed substantially between each series (P < 0.0001). Major shifts in the transcriptional landscape were identified in contour plots based on fold stimulation and hierarchical clustering. Prominent regions of transcriptional activity were evaluated for statistical enrichment to identify up-regulated pathways associated with immune response, infection and T-cell stimulation. Notably, gene enrichment was dependent on HIV-1 burden and shifted during co-infection to reveal a disproportionate effect on lymphocyte signaling, apoptosis and proteasome activity. Further evaluation of these findings may help to better understand the role of viral burden in defining cellular contribution to host immune response upon co-infection with secondary sexually transmitted pathogens.

Sensory gating is a way by which the brain manages sensory information flow. For optimal allocation of neural resources, it is important to be able to screen out (or "gate") irrelevant sensory information when another stimulus is being processed. Sensorimotor gating more generally refers to the overall process of modulation of the motor responses to sensory stimuli. Impaired sensorimotor gating is seen in a variety of neurobehavioral disorders including schizophrenia, autism and sensory processing disorder. The degree of sensorimotor gating can be studied behaviorally by indexing prepulse inhibition (PPI). PPI reflects the degree of suppression of a startle response to an intense sensory stimulus when it is preceded by a more modest sensory stimulus. The neural circuitry underlying PPI has been shown to include dopaminergic and cholinergic systems. We previously found that histaminergic H1 receptors also play important roles in sensorimotor gating: the acute administration of the histamine H1 antagonist, pyrilamine, significantly reverses the PPI impairment caused by the NMDA glutamate antagonist, dizocilpine (MK-801). The current study was conducted to determine the anatomic bases for histaminergic and cholinergic regulation of the effect of NMDA antagonism on PPI. Using autoradiography, we found that pyrilamine treatment decreased H1 receptor binding in the anterior cingulate, which correlated with PPI improvement. Furthermore, we found that pyrilamine treatment resulted in increased α7-nicotinic acetylcholine receptor binding in the insular cortex, which also correlated with PPI improvement. These findings shed light on the interaction between histamine and acetylcholine signaling in a distributed network of PPI modulation.