Importantly we present evidence for CUDC-907 1339928-25-4 neonatal overexposure to NRG1 inducing sensorimotor gating deficits in adulthood in agreement with previous data. PPI deficits as well as memory deficits are also reported in several transgenic NRG1 mouse lines as well as neonatal overexposure to EGF. Additionally, the finding of a long-term behavioral consequence of neonatal NRG1 over-exposure is convergent with previous reports and validates our use of this neonatal growth factor based peripheral injection paradigm. NRG3 overexposure during the neonatal period had lifelong effects on anxiety in adulthood as demonstrated by increased time spent in the center of the open field arena. This suggests that NRG3 is critical in the expansion of neurocircuitry involved in anxiogenesis during early postnatal development, however, further studies employing more sophisticated measures of anxiety such as elevated plus maze are warranted. Consistent with these observations, mice with decreased ErbB4 signaling show reduced anxiety levels in adulthood and mice hypomorphic for NRG3 are less anxious in response to nicotine withdrawal. While anxiety was not assessed in adult mice neonatally overexposed to NRG1, peripheral exposure to NRG1 in adult mice induces an anxiolytic phenotype, therefore, it is possible that NRG3 may also have temporally regulated effects. It is likely the neurotrophic actions of neuregulins are highly dependent upon the developmental stage of exposure, the duration of exposure and which cell types the growth factors act upon. NRG3 specifically binds to and activates ErbB4 receptors, which are exclusively expressed on inhibitory interneurons where they regulate synaptic plasticity. Consistent with overexposure to NRG1 during early development, peripheral injection of NRG3 in neonates led to social deficits in adulthood. During early neonatal development, serotonin plays a fundamental role in modulating anxiety and social behaviors. While neurotransmitter levels were not assessed in the present study, it is probable that NRG3 is important in regulating 5-HT and dopaminergic neurotransmission as has been previously demonstrated for NRG1. Additionally, 5-HT and dopamine are also important regulators of impulse control which is influenced by NRG3 expression levels in mice. The circuitry that drives social behaviors appears to be particularly sensitive to manipulation during early postnatal life with many studies demonstrating that aberrations during this critical period are linked to long lasting deficits.