Wednesday, February 23, 2011

Granule Cells (Development)

The granule cells are a type of neuron found in the granular layer of the cerebellum and dentate gyrus of the hippocampus, in the olfactory bulb, and layer IV of the cerebral cortex. Granule cells in different brain regions are both functionally and anatomically dissimilar: the only thing they have in common is that they are very small. Olfactory bulb granule cells are GABAergic and axonless, while granule cells in the dentate gyrus have long axons that project to the entorhinal cortex. Layer 4 granule cells of the cerebral cortex receive driving inputs from thalamus and convey driving inputs largely to supragranular layers 2-3, but also to infragranular layers of the cerebral cortex.

Development of granule cells in the dentate gyrus

The granule cells in the dentate gyrus are distinguished by their late time of formation during brain development. In rats, approximately 85% of the granule cells are generated after birth. In humans, it is estimated that granule cells begin to be generated during gestation weeks 10.5 to 11, and continue being generated during the second and third trimesters, after birth and all the way into adulthood. The germinal sources of granule cells and their migration pathways have been studied during rat brain development. The oldest granule cells are generated in a specific region of the hippocampal neuroepithelium and migrate into the primordial dentate gyrus around embryonic days (E) 17/18, and then settle as the outermost cells in the forming granular layer. Next, dentate precursor cells move out of this same area of the hippocampal neuroepithelium and, retaining their mitotic capacity, invade the hilus (core) of the forming dentate gyrus. This dispersed germinal matrix is the source of granule cells from that point on.

The newly generated granule cells accumulate under the older cells that began to settle in the granular layer. As more granule cells are produced, the layer thickens and the cells are stacked up according to age - the oldest being the most superficial and the youngest being deeper. The granule cell precursors remain in a subgranular zone that becomes progressively thinner as the dentate gyrus grows, but these precursor cells are retained in adult rats. These sparsely scattered cells constantly generate granule cell neurons which add to the total population. Thus, granule cells in the dentate gyrus are possibly the only known population of neurons in the brain that are constantly increasing their numbers. In 2010, it was shown that the balance between neural stem cells (NSCs) and neural progenitor cells (NPCs) is maintained by an interaction between the epidermal growth factor receptor signaling pathway and Notch signaling pathway.