Short communicationAcoustic prepulse inhibition in male and female prairie voles: Implications for models of neuropsychiatric illness
Introduction
The prairie vole (Microtus ochrogaster) has been used extensively in research on monogamy and pair-bonding due to its robust affiliative behaviors [1,2] and the relationship of the neuropeptides oxytocin and vasopressin with such behaviors [3]. Despite this strong rationale for use as a model studying social behaviors, voles have been underutilized to model social deficits in neuropsychiatric illnesses, likely due to their high behavioral and genetic heterogeneity compared to other laboratory rodents [2]. However, as recent treatments for schizophrenia and autism spectrum disorder (ASD) have targeted oxytocin as a potential therapeutic target [[4], [5], [6], [7]], the prairie vole may offer valuable insight into the neurochemistry of such mental illnesses [6,[8], [9], [10]].
The ability of the nervous system to filter out irrelevant stimuli (e.g. sensory gating) is a fundamental feature of attention and is compromised in neuropsychiatric disorders [[11], [12], [13], [14]]. Sensory gating can be seen throughout the animal kingdom, from simple invertebrates to humans [15]. The fundamentally conserved nature of sensory gating allows the systematic comparison of animal models to more complex human conditions. Prepulse inhibition (PPI), a measure of the ability to inhibit response to a startling stimulus if preceded by a weaker non-startling stimulus, is commonly used as a biomarker for disorders with dysfunctional sensory gating, such as schizophrenia, where patients show significantly less inhibition than controls [16].
In this paper, we characterize sensory gating behavior in prairie voles using the PPI procedure, a necessary first step towards modeling social and attentional deficits in ASD and schizophrenia. Habituation to the startle reflex, which is also compromised in schizophrenic patients, was assessed in the short-term (within-session) and long-term (over multiple sessions). We also compared male and female voles to determine if there were sex differences, as has been found in some strains of rodents and in humans [17,18]. Finally, we compared voles with an inbred mouse line, C57BL/6J, to determine differences in individual variability in startle responsiveness.
Section snippets
Prairie voles
The prairie vole colony was established in 2005, derived from field-caught prairie voles in Illinois. Genetic diversity was maintained through generous outside donations (2007, 2008, 2014, 2015). Voles weighed between 25–40 g and were postnatal day (P) 39–40 at time of testing. Animals were group housed with same sex littermates (2–4/cage) in temperature and humidity controlled rooms with a 14:10 light/dark cycle (lights on at 8:00 AM). Female voles were housed in a different colony room than
Male and female prairie voles show robust acoustic prepulse inhibition
There were no differences in prepulse inhibition between males and females (repeated measures ANOVA, between group effect of sex F(1,86) = 0.078, P = 0.780) (Fig. 1a). Given the lack of a sex difference, males (n = 51) and females (n = 37) were combined into one group for analysis. With males and females collapsed, each prepulse amplitude resulted in significant inhibition of the startle response compared to pulse alone (Table 1). There was a significant reduction in startle response
Discussion
Expanding upon a previous report in the literature using PPI in prairie voles [21], we found a robust inhibition of startle response to an acoustic pulse by an acoustic prepulse. Perkeybile et al. reported cross-modal potentiation (acoustic startle pulse and tactile prepulse) of startle in voles, but inhibition with a pulse and prepulse of the same modality (acoustic). We found intact PPI at all levels of prepulse tested, with PPI increasing with magnitude of prepulse. A concern for future
Funding
This work was supported by VA Biomedical Laboratory Research & Development (BLR&D) Career Development Award (CDA) # IK2 BX002712, Portland VA Research Foundation, Brain & Behavior Foundation NARSAD Award, Collins Medical Trust, and NIH EXITO Institutional Core, #UL1GM118964 to MML; NIH T32 5T32AA007468-29 and NIH T32 5T32HL083808-10 to CEJ; and NIH T32 5T32AA007468-32 to TMN.
Competing financial interests
The authors declare no competing financial interests.
Acknowledgements
The authors would like to thank Dr. Ky Dehlinger and the animal care staff at the Portland VA Veterinary Medical Unit. The authors would also like to thank Dr. Robert Hitzemann for generously donating equipment for prepulse inhibition testing. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.
References (31)
- et al.
The prairie vole: an emerging model organism for understanding the social brain
Trends Neurosci.
(2010) Association between arginine vasopressin 1a receptor (AVPR1a) promoter region polymorphisms and prepulse inhibition
Psychoneuroendocrinology
(2009)- et al.
Oxytocin and vasopressin neural networks: implications for social behavioral diversity and translational neuroscience
Neurosci. Biobehav. Rev.
(2017) - et al.
The lonely mouse: verification of a separation-induced model of depression in female mice
Behav. Brain Res.
(2010) Peripheral mechanosensory neuron dysfunction underlies tactile and behavioral deficits in mouse models of ASDs
Cell
(2016)Sensory gating in young children with autism: relation to age, IQ, and EEG gamma oscillations
Neurosci. Lett.
(2008)- et al.
P50 suppression among schizophrenia and normal comparison subjects: a methodological analysis
Biol. Psychiatry
(1997) Men are more inhibited than women by weak prepulses
Biol. Psychiatry
(1993)- et al.
Sex differences in the acoustic startle response and prepulse inhibition in Wistar rats
Behav. Brain Res.
(1999) Strain and age differences in acoustic startle responses and effects of nicotine in rats
Pharmacol. Biochem. Behav.
(1995)
The relationship of age to prepulse inhibition and habituation of the acoustic startle response
Biol. Psychol.
Sex differences in prepulse inhibition of the acoustic startle response
Personal. Individ. Diff.
Sensorimotor gating changes across the estrous cycle in female rats
Physiol. Behav.
Estrogen increases prepulse inhibition of acoustic startle in rats
Eur. J. Pharmacol.
Hormonal correlates of sexual behavior and ovulation in male-induced and postpartum estrus in female prairie voles
Physiol. Behav.
Cited by (3)
Loss of sleep when it is needed most – Consequences of persistent developmental sleep disruption: A scoping review of rodent models
2023, Neurobiology of Sleep and Circadian RhythmsCitation Excerpt :Cage manipulation includes cage-shaking using an orbital shaker (Jones et al., 2019a; Lord et al., 2022) or insertion of novel objects to force locomotion (Li et al., 2017). Cage manipulation presents the opportunity for potential automated disruption that is either continuous, targeting only the light-phase (when rodents are most likely to be asleep), and/or using closed loop delivery of disruption based on EEG/EMG activity (Jones et al., 2019a, 2019b, 2020, 2021; Lord et al., 2022; Bian et al., 2022; Feng et al., 2000; Nagai et al., 2021). An animal's cage includes its light source, the developmental chronic circadian disruption (DCCD) paradigm mimics severe shift-work with the light cycle advances dramatically every other or every fourth day (Smarr et al., 2017; Ameen et al., 2022).
Early life sleep disruption alters glutamate and dendritic spines in prefrontal cortex and impairs cognitive flexibility in prairie voles
2021, Current Research in Neurobiology
- 1
These authors contributed equally.