title: Time and time again: temporal processing demands implicate perceptual and gating deficits in the HIV-1 transgenic rat.
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.
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, University of South Carolina, 1512 Pendleton Street, Columbia, SC 29208, USA.
authors.forename: Landhing M
authors.initials: LM
authors.lastname: Moran
authors.forename: Rosemarie M
authors.initials: RM
authors.lastname: Booze
authors.forename: Charles F
authors.initials: CF
authors.lastname: Mactutus
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000818:Animals; D001307:Auditory Perception / Q000235:genetics*; D005260:Female; D015497:HIV-1 / Q000235:genetics*; D010775:Photic Stimulation / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D055139:Sensory Gating / Q000235:genetics*; D013997:Time Factors; D014796:Visual Perception / Q000235:genetics*