Rostral migratory stream

The rostral migratory stream (RMS) is a specialized migratory route found in the brain of some animals along which neuronal precursors that originated in the subventricular zone (SVZ) of the brain migrate to reach the main olfactory bulb (OB). The importance of the RMS lies in its ability to refine and even change an animal's sensitivity to smells, which explains its importance and larger size in the rodent brain as compared to the human brain, as our olfactory sense is not as developed. This pathway has been studied in the rodent, rabbit, and both the squirrel monkey and rhesus monkey. When the neurons reach the OB they differentiate into GABAergic interneurons as they are integrated into either the granule cell layer or periglomerular layer. Although it was originally believed that neurons could not regenerate in the adult brain, neurogenesis has been shown to occur in mammalian brains, including those of primates. However, neurogenesis is limited to the hippocampus and SVZ, and the RMS is one mechanism neurons use to relocate from these areas. The RMS was named and discovered by J. Altman in 1969 using 3H-thymidine autoradiography in the rat brain. He traced the migration of labeled cells from the SVZ, which is situated throughout the lateral walls of the lateral ventricles, rostrally to the main olfactory bulb. He also quantitatively studied the effect of age on the size of the RMS. There is still some ongoing debate about the extent of the RMS and adult SVZ neurogenesis of new neurons in humans. Vascular cells are known to play a prominent role in regulating proliferation of adult neural precursors. In the adult subgranular zone (SGZ), dense clusters of dividing cells were found to be anatomically close to the vasculature, especially capillaries. Contacts between adult SVZ neuronal precursors and blood vessels are unusually permeable and frequently devoid of astrocyte and pericyte interferences, suggesting that blood-derived cues are gaining direct access to adult neural precursors and their progeny. The vasculature also provides the substrate for new neuron migration after injury in the adult striatum.In the RMS, vascular cells are arranged parallel to the route of the migrating cells and provide a scaffolding. Glial cells are also associated with the blood vessels; communication between these cells may be important for RMS migration, for example, in BDNF (brain-derived neurotrophic factor), a growth factor that is thought to module RMS migration. Astrocytes form gap junctions and are closely associated with the vasculature and its basal lamina in the adult SVZ and subsequently in the RMS. They may serve as an interface to modulate influences of endothelial and circulation-derived factors as well as the availability of cytokines and growth factors in this system. In addition, astrocytes derived from the neurogenic hippocampus and SVZ, but not from the non-neurogenic spinal cord, promote proliferation and neuronal fate commitment of multipotent adult neural stem cells in culture, suggesting a role in the RMS. Astrocytes express a number of secreted and membrane-attached factors both in vitro and in vivo that are known to regulate proliferation and fate specification of adult neural precursors as well as neuronal migration, maturation, and synapse formation. In the adult SVZ, astrocytes express Robo receptors and regulate the rapid migration of SLIT1-expressing neuroblasts through the RMS. Additionally, it has been proposed that the neuroblasts themselves play a role in modulating the astrocytes through Slit-Robo interactions. In the absence of Slit, astrocytic processes do not align correctly, or create the 'tubes', instead running across the migrating neurons. Adult SVZ astrocytes also appear to release glutamate to regulate the survival of neuroblasts. Unique to the adult SVZ, ependymal cells lining the ventricular wall are in close association with neural precursors and their progeny, acting like a shield to protect the 'neurogenic niche', a zone in which stem cells are retained after embryonic development for the production of new cells of the nervous system. Ependymal cells actively regulate neuronal fate specification of adult neural precursors through release of Noggin. Beating of the cilia of ependymal cells appears to set up concentration gradients of guidance molecules, such as cytokines TNF-α (tumor necrosis factor) and IGF-1 (insulin-like growth factor), to direct migration of neuroblasts, such as in the RMS. Microglia also actively regulate adult neurogenesis. Under basal conditions, apoptotic corpses of newly generated neurons are rapidly phagocytosed from the niche by unactivated microglia in the adult SGZ. Under inflammatory conditions, reactivated microglia can have both beneficial and detrimental effects on different aspects of adult neurogenesis, depending on the balance between secreted molecules with pro- and anti-inflammatory action. In one study, the activation of microglia and recruitment of T cells were suggested to be required for enriched environment-induced SGZ neurogenesis, suggesting a possible role in the RMS. Cells in the RMS are believed to move by 'chain migration'. These neuroblasts are connected by membrane specializations including gap junctions and adherens junctions, moving along each other towards the olfactory bulb through glial tubes. The pathway and mechanisms behind this movement are a ventriculo-olfactory neurogenic system (VONS), a glial framework, and a chemotaxic cell signalling system. The olfactory system is made up in part of the RMS which stretches from the subventricular zone in the wall of the lateral ventricle, through the basal forebrain, to the olfactory bulb (OB). VONS is the name given to this pathway, and it consists of the subventricular zone, the RMS, the olfactory tract and the olfactory bulb. Developing neurons leave the subventricular zone and enter the RMS and travel caudally and ventrally along the undersurface of the caudate nucleus; this is referred to as the descending limb. Upon reaching the ventral side of the caudate nucleus, the neurons follow the rostral limb and travel ventrally and rostrally, entering the anterior olfactory cortex (AOC). The AOC gives rise to the olfactory tract, which ends in the olfactory bulb.