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Time and Time Again: Temporal Processing Demands Implicate Perceptual and Gating Deficits in the HIV-1 Transgenic Rat

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Abstract

HIV-1-associated neurocognitive disorders (HAND) afflict up to 50 % of HIV-1+ individuals, despite the effectiveness of combination antiretroviral therapy (CART) in reducing the prevalence of more severe neurocognitive impairment. Alterations in brainstem auditory evoked potentials (BAEP), a measure of temporal processing, are one of the earliest neurological abnormalities of HIV-1-positive individuals. Prepulse inhibition (PPI) of the auditory startle response (ASR), a measure of sensorimotor gating, was studied in HIV-1 transgenic (Tg) rats, which express 7 of the 9 HIV-1 genes. Ovariectomized female Fischer HIV-1 Tg and control rats (ns = 41–42) were tested for PPI at three test periods, with at least 2 months separating each test period, using auditory and visual prepulses, an auditory startle stimulus, and interstimulus intervals (ISI) ranging from 0 to 4000 msec. Auditory and visual prepulse trial blocks were presented in counterbalanced order. For both auditory and visual prepulses, HIV-1 Tg animals exhibited a flatter ISI function, which did not sharpen with age, as it did in controls. Over time, auditory prepulses precipitated a temporal shift in peak inhibition in HIV-1 Tg animals relative to controls, whereas with visual prepulses, both groups displayed peak inhibition at the 40 msec ISI. A lack of perceptual sharpening with age and a relative insensitivity to the temporal dimension of sensorimotor gating are evident in the HIV-1 Tg rat prior to clinical signs of wasting. Deficits in sensorimotor gating may not only provide an early subtle diagnostic marker of HAND, but may also afford a key target for development of potential therapeutics.

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Acknowledgments

This research was supported by the National Institute on Drug Abuse [RMB, Grant DA013137; CFM, Grant DA031604] and by the National Institute of Child Health and Human Development [CFM, Grant HD043680].

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The authors declare that they have no conflict of interest.

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  1. Department of Psychology, Behavioral Neuroscience Program, University of South Carolina, 1512 Pendleton Street, Columbia, SC, 29208, USA

    Landhing M. Moran, Rosemarie M. Booze & Charles F. Mactutus

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  1. Landhing M. Moran
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Correspondence to Charles F. Mactutus.

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Moran, L.M., Booze, R.M. & Mactutus, C.F. Time and Time Again: Temporal Processing Demands Implicate Perceptual and Gating Deficits in the HIV-1 Transgenic Rat. J Neuroimmune Pharmacol 8, 988–997 (2013). https://doi.org/10.1007/s11481-013-9472-6

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