Ultrasonic vocalization emission is altered following neonatal hypoxic-ischemic brain injury in mice

Neonatal hypoxic-ischemic (HI) brain injury leads to cognitive impairments including social communication disabilities. Current treatments do not sufficiently target these impairments, therefore new tools are needed to examine social communication in models for neonatal brain injury. Ultrasonic vocalizations (USVs) during early life show potential as a measurement for social development and reflect landmark developmental stages in neonatal mice. However, changes in USV emission early after HI injury have not been found yet. Our current study examines USV patterns and classes in the first 3 days after HI injury. C57Bl/6 mice were subjected to HI on postnatal day (P)9 and USVs were recorded between P10 and P12. Audio files were analyzed using the VocalMat automated tool. HI-injured mice emitted less USVs, for shorter durations, and at a higher frequency compared to control (sham-operated) littermates. The HI-induced alterations in USVs were most distinct at P10 and in the frequency range of 50-75 kHz. At P10 HI-injured mouse pups also produced different ratios of USV class types compared to control littermates. Moreover, alterations in the duration and frequency were specific to certain USV classes in HI animals compared to controls. Injury in the striatum and hippocampus contributed most to alterations in USV communication after HI. Overall, neonatal HI injury leads to USV alterations in newborn mice which could be used as a tool to study early HI-related social communication deficits.