The cerebral cortex comprises over three quarters of the brain, and serves as structural basis for the sophisticated perceptual and cognitive functions. It develops from common multipotent neural stem cells (NSCs) that line the neural tube. Development of the NSCs encompasses sequential phases of progenitor expansion, neurogenesis, and gliogenesis along with the progression of developmental stages. Interestingly, NSCs steadfastly march through all of these phases and give rise to specific neural cell types in a temporally defined and highly predictable manner. Herein, we delineate the intrinsic and extrinsic factors that dictate the progression and tempo of NSC differentiation during cerebral cortex development, and how epigenetic modifications contribute to the dynamic properties of NSCs.

SUMMARY1. The effects of local applications of prostaglandin E2 (PGE2) on the unit activity of fifty-one neurones in the organum vasculosum lamina terminalis (OVLT) region and fifty-eight neurones in the preoptic area (POA) were investigated in small tissue slices from the rat hypothalamus containing the OVLT and POA isolated from each other.2. Of these, thirty OVLT and twenty-eight POA neurones were warm sensitive and increased their discharge rate in response to a rise in tissue temperature. One OVLT neurone and one POA neurone were cold sensitive and showed the opposite type of responses to changes in temperature. The thermosensitivity of these neurones was still observed in a Ca21 free-high Mg2+ solution.3. Perfusion with PGE2 in doses between 1 and 250 nm changed the discharge rate in forty-two of fifty-one OVLT neurones and in thirty-two of fifty-eight POA neurones in a dose-dependent manner. The responses to PGE2 were not lost during synaptic blockade. The threshold dose of PGE2 to alter the discharge rate of the OVLT neurones (4-8+1-1 (S.E.M.) nM, n = 16) was significantly lower than that of the POA neurones (40 9 + 12 2 nm, n = 16).4. Fifteen of forty-two OVLT neurones exhibited the responses with a slower onset (latency 5-13 min) and a longer duration (20 min to 3 h), but such responses were observed in only one of thirty-two POA neurones.5. The responses of OVLT and POA neurones to PGE2 (50-250 nm) were reversibly blocked by a concurrent application of AH6809. a prostanoid EP, and/or a DP receptor antagonist.6. While there was no clear correlation between the type of thermosensitivity and the type of response to PGE2 among the POA neurones, a significantly higher incidence of inhibitory response to PGE2 was found among the warm-sensitive neurones in the OVLT region.7. The lower threshold responses to PGE2 and the higher incidence of PGE2 responsiveness among OVLT neurones are consistent with previous findings which showed that the highest density of PGE2 receptor binding and the highest pyrogenic sensitivity to microinjected PGE2 were observed in the OVLT region. The results MS 9526

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Adult neurogenesis persists throughout life in the dentate gyrus (DG) of the hippocampus, and its importance has been highlighted in hippocampus-dependent learning and memory. Adult neurogenesis consists of multiple processes: maintenance and neuronal differentiation of neural stem/precursor cells (NS/PCs), followed by survival and maturation of newborn neurons and their integration into existing neuronal circuitry. However, the mechanisms that govern these processes remain largely unclear. Here we show that DNA methyltransferase 1 (DNMT1), an enzyme responsible for the maintenance of DNA methylation, is highly expressed in proliferative cells in the adult DG and plays an important role in the survival of newly generated neurons. Deletion of Dnmt1 in adult NS/PCs (aNS/PCs) did not affect the proliferation and differentiation of aNS/PCs per se. However, it resulted in a decrease of newly generated mature neurons, probably due to gradual cell death after aNS/PCs differentiated into neurons in the hippocampus. Interestingly, loss of DNMT1 in post-mitotic neurons did not influence their survival. Taken together, these findings suggest that the presence of DNMT1 in aNS/PCs is crucial for the survival of newly generated neurons, but is dispensable once they accomplish neuronal differentiation in the adult hippocampus.

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