Early-life stressful social experience (SSE) alters ultrasound vocalizations and impairs novel odor preference: Influence of histone dopaminylation.

Background And Aim: Rat pups emit ultrasound vocalizations (USVs) in response to negative/positive stimuli, the acoustic features of USVs are altered during the stressful and threatening situation. We hypothesize that maternal separation (MS) and/or stranger (St) exposure would alter acoustic features of USVs, neurotransmitter transmission, epigenetic status and impaired odor recognition later in life.

Method: Rat pups were left undisturbed in the home cage (a) control, (b) pups were separated from mother MS [postnatal day (PND) 5-10], (c) intrusion of stranger (St; social experience: SE) to the pups either in the presence of mother (M + P + St) or (d) absence of mother (MSP + St). USVs was recorded on PND10 in two context i) five minutes after MS, MS and St, mother with their pups and St, ii) five minutes after the pups reunited with their pups and/or removal of stranger. Novel odor preference test was conducted during their mid-adolescence on PND34, 35.

Results: Rat pups produced two complex USVs (frequency step-down: 38-48 kHz; and two syllable: 42-52 kHz) especially when the mother was absent and the stranger was present. Further, pups failed to recognize novel odor, which can be linked to an increased dopamine transmission, decreased transglutaminase (TGM)-2, increased histone trimethylation (H3K4me3) and dopaminylation (H3Q5dop) in the amygdala.

Conclusions: This result suggest that USVs act as acoustic code of different early-life stressful social experience, which appears to have long-term effect on odor recognition, dopaminergic activity and dopamine dependent epigenetic status.