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Habituation and Prepulse Inhibition of Acoustic Startle in Rodents
Published on: September 1, 2011
Neonatal hippocampal Tat injections: developmental effects on prepulse inhibition (PPI) of the auditory startle
Sylvia Fitting1, Rosemarie M Booze, Charles F Mactutus
1Department of Psychology, University of South Carolina, Columbia, SC 29208, USA. fitting@sc.edu
Insights
HIV-1 Tat toxin exposure in neonatal rats alters sensorimotor gating (PPI) in a sex-specific manner. These developmental brain effects persist with age, indicating potential long-term impacts of vertical HIV transmission.
Area of Science:
- Neuroscience
- Developmental Biology
- Infectious Diseases
Background:
- Children living with HIV and AIDS (2.2 million) are primarily infected through mother-to-child transmission.
- HIV-1 infection timing may influence the onset and progression of central nervous system (CNS) disease.
- HIV's brain effects are hypothesized to be mediated by viral toxins like Tat and gp120.
Purpose of the Study:
- To characterize the developmental effects of the HIV-1 Tat toxin on prepulse inhibition (PPI) of the auditory startle response (ASR).
- To investigate potential sex-specific differences in the impact of Tat on sensorimotor gating.
- To assess the persistence of Tat-induced effects on PPI from early development into adulthood.
Main Methods:
- Intrahippocampal administration of Tat or saline to neonatal (postnatal day 1) Sprague-Dawley rat pups.
- Longitudinal testing of PPI at postnatal days 30, 60, and 90, using various inter-stimulus intervals (ISIs).
- Cross-sectional testing at day 90 to evaluate age-related effects and the impact of repeated testing.
Main Results:
- Tat administration altered PPI in a sex-dependent manner.
- Male rats showed a leftward shift in ISI for maximal inhibition on days 30 and 60, but not 90.
- Female rats exhibited altered peak ASR latency across multiple ISIs at all testing ages, indicating less PPI modulation.
Conclusions:
- Neonatal hippocampal Tat exposure induces alterations in sensorimotor gating (PPI) in rats.
- The observed effects are sex-specific and suggest differential developmental trajectories.
- Adverse Tat effects are maintained with age, with diminished longitudinal effects attributed to repeated testing rather than recovery.
Abstract:
The current estimate of children (<15 years) living with HIV and AIDS is 2.2 million. The major source of infection occurs through vertical transmission of the virus from mother to child during delivery [UNAIDS/WHO, 2005. AIDS Epidemic Update. UNAIDS, Geneva]. Recent studies have shown that timing of HIV-1 infection might be related to the onset and rate of progression of CNS disease. The effects of HIV on the brain are thought to be mediated indirectly through the viral toxins Tat and gp120. This study characterized developmental effects on PPI following intrahippocampal administration of Tat. On postnatal day (P)1, one male and one female pup from each of eight Sprague-Dawley litters were bilaterally injected with 50 microg Tat or saline (1 microl volume). Animals were tested for PPI of the auditory startle response (ASR) (ISIs of 0, 8, 40, 80, 120, and 4000 ms, six trial blocks, Latin-square design) on days 30, 60 and 90. Tat altered PPI and the pattern of alterations was different for males and females. For males, a leftward shift was evident in the ISI for maximal inhibition of the response on day 30 and on day 60 (chi(2)(1)=4.7, p< or =.03, and chi(2)(1)=5.3, p< or =.02, respectively), but not on day 90. For females, Tat altered peak ASR latency across PPI trials (8-120 ms) at all days of testing (30, 60, and 90 days of age), as indexed by orthogonal component analyses, indicating less modulation of PPI by ISI. Data collected from a second group that were tested only once at 90 days of age, suggested that the observed adverse Tat effects for males and females early in development were maintained with age. Thus, the diminishing TAT effect on PPI at day 90 in a longitudinal study design was attributed to repeated testing, rather than 'recovery of function'. Collectively, the data suggested that hippocampal Tat injections in neonatal rats produced alterations in the pre-attentive process of sensorimotor gating, as indexed by PPI.
