Neural mechanisms underlying stress resilience in Ahi1 knockout mice: relevance to neuropsychiatric disorders.

The Abelson helper integration site 1 (AHI1) gene has a pivotal role in brain development. Studies by our group and others have demonstrated association of AHI1 with schizophrenia and autism. To elucidate the mechanism whereby alteration in AHI1 expression may be implicated in the pathogenesis of neuropsychiatric disorders, we studied Ahi1 heterozygous knockout (Ahi1(+/-)) mice. Although their performance was not different from wild-type mice on tests that model classical schizophrenia-related endophenotypes, Ahi1(+/-) mice displayed an anxiolytic-like phenotype across different converging modalities. Using behavioral paradigms that involve exposure to environmental and social stress, significantly decreased anxiety was evident in the open field, elevated plus maze and dark-light box, as well as during social interaction in pairs. Assessment of core temperature and corticosterone secretion revealed a significantly blunted response of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis in Ahi1(+/-) mice exposed to environmental and visceral stress. However, response to centrally acting anxiogenic compounds was intact. On resting-state functional MRI, connectivity of the amygdala with other brain regions involved in processing of anxiogenic stimuli and inhibitory avoidance learning, such as the lateral entorhinal cortex, ventral hippocampus and ventral tegmental area, was significantly reduced in the mutant mice. Taken together, our data link Ahi1 under-expression with a defect in the process of threat detection. Alternatively, the results could be interpreted as representing an anxiety-related endophenotype, possibly granting the Ahi1(+/-) mouse relative resilience to various types of stress. The current knockout model highlights the contribution of translational approaches to understanding the genetic basis of emotional regulation and its associated neurocircuitry, with possible relevance to neuropsychiatric disorders.

[The mission of the Director General of the Ministry of Health]. / Les missions de la direction générale de la santé (DGS).

In France, the health and solidarity department of Employment and solidarity Ministry have just been re-organised. The Directory General of the department of Health is experiencing a complete revision of its functions and organisation. This article presents the public health context which has been taken into account for this new organisation and explains its main principles and strategic orientations. The new organisation chart is clarified. It is made up by two departments and seven under-directions. Up to now, control and administrative supervision were predominant among Health General Direction functions. They are now oriented to administrate missions prioritizing the function of health doctrines' elaboration, of programmation, animation and coordination. As the guarantor of sanitary security, the Health General Direction has also to impulse a new partnership which does not only include health professional, social and health organisation and the economic actors: citizen in general and service users in particular have to be included to promote health democracy.