Electroencephalographic and early communicative abnormalities in Brattleboro rats

Abstract

Reductions in the levels of the neuropeptide vasopressin (VP) and its receptors have been associated with schizophrenia. VP is also critical for appropriate social behaviors in humans as well as rodents. One of the prominent symptoms of schizophrenia is asociality and these symptoms may develop prodromally. A reduction in event-related potential (ERP) peak amplitudes is an endophenotype of schizophrenia. In this study, we use the Brattleboro (BRAT) rat to assess the role of VP deficiency in vocal communication during early development and on auditory ERPs during adulthood. BRAT rats had similar vocal communication to wild-type littermate controls during postnatal days 2 and 5 but the time between vocalizations was increased and the power of the vocalizations was reduced beginning at postnatal day 9. During adulthood, BRAT rats had deficits in auditory ERPs including reduced N40 amplitude and reduced low and high gamma intertrial coherence. These results suggest that the role of VP on vocal communication is an age-dependent process. Additionally, the deficits in ERPs indicate an impairment of auditory information processing related to the reduction in VP. Therefore, manipulation of the VP system could provide a novel mechanism for treatment for negative symptoms of schizophrenia.

Differential sensitivity of the Brattleboro rat to glutamatergic and dopaminergic perturbation

“…This inconsistency is likely due to differences in the method of PPI measurement. For example, we previously demonstrated that BRAT rats are insensitive to alterations in prepulse intensity, but do display differences in sensitivity to prepulse interval [61]. Consistent with previous studies, MK801 caused a reduction in PPI [62] and caused socially induced USVs (Table 1).…”

“…BRAT rats did not have baseline PPI impairments, consistent with some previously published reports [44,61] but inconsistent with others [29,54,55]. This inconsistency is likely due to differences in the method of PPI measurement.…”

Atypical Social Development in Vasopressin-Deficient Brattleboro Rats

“…The Brattleboro mutation also affects USVs. Infant Hom Brattleboro pups emit fewer maternal separation-induced 40 kHz USVs ( Lin et al, 2013 ; Varga et al, 2015 ). Here, we demonstrate that USV deficits of Hom Brattleboro rats persist into the juvenile stage and include prosocial vocalizations.…”

“…These rats have a single base pair deletion in exon 2 of the Avp gene that disrupts the production of AVP ( Schmale and Richter, 1984 ). The behavior of adult homozygous Brattleboro (Hom) rats has been well studied, and deficits have been found in the major functions assigned to AVP, including social behaviors such as social recognition/discrimination ( Engelmann and Landgraf, 1994 ; Feifel et al, 2009 ) and social interactions ( Lin et al, 2013 ). Studies on the behavioral development of Brattleboro rats have been confined to early postnatal life (first 2 weeks of life; Zelena et al, 2008 ; Lin et al, 2013 ).…”

“…The behavior of adult homozygous Brattleboro (Hom) rats has been well studied, and deficits have been found in the major functions assigned to AVP, including social behaviors such as social recognition/discrimination ( Engelmann and Landgraf, 1994 ; Feifel et al, 2009 ) and social interactions ( Lin et al, 2013 ). Studies on the behavioral development of Brattleboro rats have been confined to early postnatal life (first 2 weeks of life; Zelena et al, 2008 ; Lin et al, 2013 ). Infant Hom rats exhibit decreased aggregation ( Schank, 2009 ) and emit fewer maternal separation-induced USVs ( Varga et al, 2015 ), suggesting that the development of social behaviors might be affected by the Brattleboro mutation.…”