| In the rat dentate gyrus, unlike most mammalian brain regions, neurons and glia continue to be produced well into adulthood. This unusual pattern of development makes the dentate gyrus an interesting and useful system in which to study the factors that regulate neurogenesis. The work presented here examines and characterizes the regulation of neurogenesis in the adult rat dentate gyrus using {dollar}sp3{dollar}H-thymidine autoradiography combined with immunohistochemistry.; Dividing cells in the adult rat dentate gyrus ({dollar}sp3{dollar}H-thymidine labeled cells 1 hour after injection) did not express the specific neuronal marker, neuron specific enolase (NSE), whereas some dividing cells expressed the glial marker, glial fibrillary acidic protein (GFAP), indicating that immature precursors and glia, but not mature neurons, divide in this region. However, the majority of newly born cells were NSE-immunoreactive 3-4 weeks after cell division, indicating that many immature precursors differentiate into neurons during this time. Some cells were born locally in the granule cell layer while others arose from the hilus and migrated to the granule cell layer.; The rate of neurogenesis in the adult rat dentate gyrus was found to be dependent upon the levels of circulating adrenal steroids; corticosterone significantly decreased cell birth in the dentate gyrus, while removal of endogenous adrenal steroids increased the birth of neurons.; Further studies demonstrated that neurogenesis in the adult dentate gyrus of the rat is regulated by afferent input, via NMDA receptors. Activation of NMDA receptors rapidly decreased cell birth, whereas deactivation of NMDA receptors, through removal of perforant path input or pharmacological blockade, increased cell birth in this region. Many cells born following acute NMDA receptor blockade differentiated into mature neurons, which produced an increase in the overall density of neurons in the granule cell layer.; Since both adrenal steroids and excitatory amino acids are increased in response to stress, these results present a possible mechanism through which environmental factors could determine the number and age of neurons in the adult dentate gyrus, a brain region involved in defensive behavior and spatial learning. |
