Granule cells in the olfactory bulb (OB) are continually produced and added into the neuronal circuit in the adult brain. Sensory input to the OB plays a key role in the survival of newly generated granule cells. Here, we examined in the adult mice whether there is a time window after the generation of new granule cells when their survival is strongly influenced by sensory input. New granule ce...

The neuronal circuits of the cerebellar cortex are essential for motor and sensory learning, associative memory formation, and the vestibular ocular reflex. In children and young adults, tumors of the granule cell, the medulloblastomas, represent 40% of brain tumors. We report the differentiation of E14 ES cells into mature granule neurons by sequential treatment with secreted factors (WNT1, FG...

A substantial fraction of adult-generated granule cells in the dentate gyrus survive and integrate into the existing neuronal network. These newborn neurons must navigate the environment of the adult brain, a setting that is presumably less optimized for neuronal maturation compared with that in the developing brain. We used EGFP (enhanced green fluorescent protein) expression in newborn granul...

Mossy fiber sprouting is a form of synaptic reorganization in the dentate gyrus that occurs in human temporal lobe epilepsy and animal models of epilepsy. The axons of dentate gyrus granule cells, called mossy fibers, develop collaterals that grow into an abnormal location, the inner third of the dentate gyrus molecular layer. Electron microscopy has shown that sprouted fibers from synapses on ...

It is known that cerebellar granule cells are powerful inducers for the differentiation of Purkinje cells. However, the detailed mechanism of this regulation has not yet been clarified. Here, using cerebellar neuronal culture, we show that the activation of NMDA receptors expressed by granule cells triggers the signaling pathway for the dendritic differentiation of Purkinje cells. This signal h...

The developing cerebellum expresses genes which encode for both neurotrophins and their receptors. The present study was designed to determine at what stages during cerebellar granule cell neurogenesis neurotrophin family molecules may act. We report here that in purified, well-characterized granule cell cultures (Gao et al., 1991; 1992), none of the neurotrophins stimulated proliferation of gr...

Effects of formulation parameters on the fractional release profile of diclofenac sodium from matrices having the manufacturing formulation ingredients are studied. As a content of cetyl alcohol (rate controlling agent) in the matrix increases, the fractional release decreases. The fractional release increases either by increasing sucrose content outside the granule or by decreasing sucrose...

In the cerebellar circuit, Golgi cells are thought to contribute to information processing and integration via feedback mechanisms. In these mechanisms, dynamic modulation of Golgi cell excitability is necessary because GABA from Golgi cells causes tonic inhibition on granule cells. We studied the role and synaptic mechanisms of postsynaptic metabotropic glutamate receptor subtype 2 (mGluR2) at...

One potential mechanism of temporal lobe epilepsy is recurrent excitation of dentate granule cells through aberrant sprouting of their axons (mossy fibers), which is found in many patients and animal models. However, correlations between the extent of mossy fiber sprouting and seizure frequency are weak. Additional potential sources of granule cell recurrent excitation that would not have been ...

Wnt genes encode secreted proteins implicated in cell fate changes during development. To define specific cell populations in which Wnt genes act, we have examined Wnt expression in the cerebellum. This part of the brain has a relatively simple structure and contains well-characterized cell populations. We found that Wnt-3 is expressed during development of the cerebellum and that expression is...