Prefrontal cortex-dependent innate behaviors are altered by selective knockdown of Gad1 in neuropeptide Y interneurons.

GABAergic dysfunction has been implicated in a variety of neurological and psychiatric disorders, including anxiety disorders. Anxiety disorders are the most common type of psychiatric disorder during adolescence. There is a deficiency of GABAergic transmission in anxiety, and enhancement of GABA transmission through pharmacological means reduces anxiety behaviors. GAD67-the enzyme responsible for GABA production-has been linked to anxiety disorders. One class of GABAergic interneurons, Neuropeptide Y (NPY) expressing cells, is abundantly found in brain regions associated with anxiety and fear learning, including prefrontal cortex, hippocampus and amygdala. Additionally, NPY itself has been shown to have anxiolytic effects, and loss of NPY+ interneurons enhances anxiety behaviors. A previous study showed that knockdown of Gad1 from NPY+ cells led to reduced anxiety behaviors in adult mice. However, the role of GABA release from NPY+ interneurons in adolescent anxiety is unclear. Here we used a transgenic mouse that reduces GAD67 in NPY+ cells (NPYGAD1-TG) through Gad1 knockdown and tested for effects on behavior in adolescent mice. Adolescent NPYGAD1-TG mice showed enhanced anxiety-like behavior and sex-dependent changes in locomotor activity. We also found enhancement in two other innate behavioral tasks, nesting construction and social dominance. In contrast, fear learning was unchanged. Because we saw changes in behavioral tasks dependent upon prefrontal cortex and hippocampus, we investigated the extent of GAD67 knockdown in these regions. Immunohistochemistry revealed a 40% decrease in GAD67 in NPY+ cells in prefrontal cortex, indicating a significant but incomplete knockdown of GAD67. In contrast, there was no decrease in GAD67 in NPY+ cells in hippocampus. Consistent with this, there was no change in inhibitory synaptic transmission in hippocampus. Our results show the behavioral impact of cell-specific interneuron dysfunction and suggest that GABA release by NPY+ cells is important for regulating innate prefrontal cortex-dependent behavior in adolescents.

Predictive value of hearing assessment by the auditory brainstem response following universal newborn hearing screening.

OBJECTIVE: This study set out to determine the accuracy with which tone pip ABR and click ABR, carried out in babies referred from universal newborn hearing screening, is able to predict the hearing outcome as determined by follow-up hearing tests. STUDY SAMPLE: The cohort of babies studied were all babies referred for hearing assessment from the universal newborn hearing screen in Sheffield, UK for the period January 2002 to September 2007, who were found to have a significant hearing impairment. DESIGN: The results of hearing assessment following referral from the newborn hearing screen were collected together with those of follow-up tests carried out up to an age when behavioural testing had established ear- and frequency-specific thresholds at 0.5, 1, 2 and 4 kHz. RESULTS: The standard deviation of the difference between the follow up and the tone pip ABR thresholds was 10.5 dB for the 4-kHz tone pip, 16.8 dB for the 1-kHz tone pip, and ranged between 21.7 and 24.7 dB for click ABR. CONCLUSIONS: The results of the study show that tone pip ABR following referral from newborn hearing screening has a similar accuracy to that reported in older subjects, and is a much better predictor compared to click ABR.