Hypoxic-ischemic (HI) brain injury from perinatal asphyxia affects approximately 0.15% of live births in developed countries, leading to persistent cognitive and social communication impairments in 20–50% of surviving infants. Among these, 17% develop language disabilities by age two. A better understanding of how neonatal brain injury affects social communication is needed to effectively target these impairments and develop therapeutics. However, social communication in neonatal HI animal models is understudied. A recent study published in Behavioural Brain Research shows significant alterations in ultrasonic vocalizations (USVs) in neonatal mice following HI brain injury.

The study involved C57Bl/6 mice subjected to HI on postnatal day (P)9, with USVs recorded from P10 to P12 using the VocalMat automated tool as well as analysis of histological changes in the brain 4 weeks after injury. Multiple brain areas were affected by HI, with the hippocampus showing the largest neuronal damage. As for vocalizations, HI-injured mice emitted fewer USVs, with shorter durations and higher frequencies compared to sham-operated controls. These alterations were most pronounced at P10, particularly in the 50–75 kHz frequency range. Dams tend to respond better to longer calls with a lower frequency. Therefore, these alterations in the call profile might inhibit maternal care with pups being unable to produce distress calls. Additionally, the ratios of USV class types differed significantly between HI-injured and control mice. Further analysis showed that specific USV classes exhibited distinct changes in duration and frequency due to HI injuries. This altered vocal phenotype suggests possible emotional deficits, damage to the vocal circuitry in the brain, or both. Additionally, the damage in the striatum and hippocampus correlated with these USV alterations. This suggests that neonatal HI injury affects brain regions critical for vocal communication, highlighting USVs as a valuable tool for studying early social communication deficits.

Given that HI injury affects brain regions integral to USV production, such as the thalamus, hippocampus, hypothalamus, and cerebral cortex, the study shows the potential of USVs to model vocal and social behavior impairments. This novel approach could facilitate the development of targeted interventions to mitigate social communication disabilities in affected infants.

Original reference: Hermans, E.C. et al. Behav. Brain Res. 471, 115113 (2024)