Although the basic structure and connectivity of the brain are completed by the time of birth, the brain undergoes substantial development during the postnatal period. Evidence indicates that a number of diseases begin during this developmental period, many months after birth. These include various forms of anxiety and mood disorders (depression, attention deficit and hyperactivity disorders (ADHD) and certain forms of mental retardation.

Our group is interested in developmental processes that are involved in establishing adult behavior (temperament, mood etc.) and how these processes go awry in neuropsychiatric diseases, specifically in anxiety disorders and fragile X syndrome.

Several lines of evidence indicate that the level of fear/anxiety (e.g. reaction to stressful stimuli, environment or situation) is established during postnatal development and once the level is set, it is stable through life. Both genetic and environmental factors shape the individual level of fear/anxiety. In our research we extensively use mouse targeted mutants that have an increased or decreased anxiety related behavior. For example the mouse mutants deficient in the serotonin 1A (5-HT1A) receptor and tumor necrosis factor alpha (TNF) have elevated and reduced levels of anxiety, respectively. Another mouse strain, that is a model of the fragile X syndrome, has a characteristic hyperactivity similar to that seen in ADHD and autism. These mutants are used to elucidate the molecular and cellular mechanisms underlying anxiety, hyperactivity and other psychiatric symptoms.

The work in our laboratory is currently focused on the following projects:

* 5-HT1A receptor-mediated regulation of hippocampal morphogenesis during postnatal development. Data indicate that a developmental delay of the ventral hippocampus is responsible, at least partly, for the increased fear related behavior of 5-HT1A receptor deficient mice.
* The neurobiological basis of the reduced anxiety of TNF deficient mice seems to be associated with an accelerated development of the ventral hippocampus. Reduced anxiety, similarly to increased anxiety, is maladaptive and may underlie conditions such as risk taking behavior.
* We are also interested in the long-term effects of antidepressant and psychostimulant use in children and adolescents. Our data suggest that these drugs have a significant impact on the developing brain in mice, manifested in behavioral abnormalities in adulthood.
* The hyperactivity of fragile X deficient mice seems to be related to the abnormal regulation of a specific dopamine receptor. We are studying the underlying mechanism and try to normalize dopamine neurotransmission during postnatal development to rescue the behavioral phenotype of the mutant mice.

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