Human genetic data on psychiatric disorders repeatedly demonstrate the
involvement of various genes that are associated with neural development and
neurogenesis. Neurogenesis is a biological process that is critical in brain development
and continues throughout life. Neurogenesis is a multi-step process starting from the
division of neural stem cells/progenitor cells, leading to self-renewal and simultaneously
to the production of lineage-committed cells, including neurons and glial cells. Minor
defects in the neurogenesis process, such as production of fewer new neurons and
malformation of neural circuits, could represent phenotypes of psychiatric disorders at
molecular and cellular levels in animal models (here termed as “microphenotypes”).
However, microphenotypes are not easily used as biomarkers. We have focused on a
physiological condition, sensorimotor gating deficits, that can be scored by a prepulse
inhibition (PPI) test. Impaired PPI is considered to be one of the compelling endophenotypes (biological
markers) of mental disorders such as schizophrenia, autism, and other neurodevelopmental disorders.
Because the neural circuit for PPI involves the hippocampus, a unique brain region where neurogenesis occurs
postnatally, we hypothesize that an impairment of preadolescent neurogenesis is critical for the onset of
sensorimotor gating defects. To test this hypothesis, we investigated a critical period of neurogenesis that can
affect PPI. In this paradigm, we introduced an enriched environment to restore neurogenesis, thereby
recovering PPI deficits in mice. We noted impairments in the maturation of newborn neurons in the
hippocampal dentate gyrus (DG) and GABAergic neurons in the hippocampus, which could be considered as
microphenotypes associated with PPI defects. More precise genetically controlled neurogenesis models (with
precise time points or periods) are needed to be studied in further investigation to support our hypothesis.