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Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, are observed in neurodevelopmental and neuropsychiatric disorders. Despite the large PPI literature, the majority of studies characteristically employ tests with one interstimulus interval (ISI), of one modality, at one age. In the context of the auditory startle response (ASR), the present study examined (1) the profile for the ontogeny of PPI through adulthood in Long-Evans hooded rats with a reasonably comprehensive ISI function, (2) whether the ontogenetic profile for PPI is sensitive to modality of the prepulse stimulus, as a within-session variable, and (3) whether the maturation of PPI differs for males and females. Despite the basic effect of more pronounced PPI in adult relative to preweanling animals, each sensory modality displayed a unique ontogenetic profile for PPI, without any compelling evidence for major differences between males and females, in accordance with the known temporal course of peripheral and central maturational profiles of sensory systems in the rat. The context for assessing auditory PPI (auditory and tactile vs. auditory and visual prepulses) influenced the overall startle response, i.e., a shift in the height of the entire profile, but did not significantly impact the auditory PPI profile per se. The translational relevance of preclinical sensorimotor assessments to patients with neurodevelopmental and/or neuropsychiatric disorders depends partly on an understanding of the ontogeny of sensorimotor gating in different sensory systems, and can be strengthened with the use of a reasonably comprehensive number of ISIs to provide relatively precise and defined response functions.

Pediatric AIDS caused by human immunodeficiency virus type 1 (HIV-1) remains one of the leading worldwide causes of childhood morbidity and mortality. HIV-1 proteins, such as Tat and gp120, are believed to play a crucial role in the neurotoxicity of pediatric HIV-1 infection. Detrimental effects on development, behavior, and neuroanatomy follow neonatal exposure to the HIV-1 viral toxins Tat1-72 and gp120. The present study investigated the neurobehavioral effects induced by the HIV-1 neurotoxic protein Tat1-86, which encodes the first and second exons of the Tat protein. In addition, the potential effects of HIV-1 toxic proteins Tat1-86 and gp120 on inflammatory pathways were examined in neonatal brains. Vehicle, 25 μg Tat1-86 or 100 ng gp120 was injected into the hippocampus of male Sprague-Dawley pups on postnatal day 1 (PD1). Tat1-86 induced developmental neurotoxic effects, as witnessed by delays in eye opening, delays in early reflex development and alterations in prepulse inhibition (PPI) and between-session habituation of locomotor activity. Overall, the neurotoxic profile of Tat1-86 appeared more profound in the developing nervous system in vivo relative to that seen with the first exon encoded Tat1-72 (Fitting et al., 2008b), as noted on measures of eye opening, righting reflex, and PPI. Neither the direct PD1 CNS injection of the viral HIV-1 protein variant Tat1-86, nor the HIV-1 envelope protein gp120, at doses sufficient to induce neurotoxicity, necessarily induced significant expression of the inflammatory cytokine IL-1β or inflammatory factors NFκ-β and Iκ-β. The findings agree well with clinical observations that indicate delays in developmental milestones of pediatric HIV-1 patients, and suggest that activation of inflammatory pathways is not an obligatory response to viral protein-induced neurotoxicity that is detectable with behavioral assessments. Moreover, the amino acids encoded by the second tat exon may have unique actions on the developing hippocampus.