In rat hippocampal slices, Perea and Araque  showed that astrocytes not only respond differently to glutamate and acetylcholine, but also to glutamate released from the Schaeffer collaterals compared to glutamate from the alveus terminals. disease, epilepsy, and schizophrenia. work has been utilized and where helpful, other reviews have been referenced to provide the reader with understanding on topics beyond the scope of this work. ASTROCYTES AS DIVERSE NEURAL CIRCUIT ELEMENTS A pervading thought in neuroscience, and more specifically, glia research, is usually that neuroglia outnumber neurons 10:1 . Recent evidence, however, shows that this number may be vastly overestimated. Using isotropic fractionation of human brain samples combined with NeuN nuclei labelling, research now establishes the ratio of neuronal to non-neuronal cells is usually closer to 1:1 . This ratio is in line with other studies . Interestingly, these studies also found that this ratio varies throughout the brain. In cerebral cortex, there is an increase in glia relative to neurons whereas in the cerebellum it is the opposite [2,3]. While the exact reasons for these shifts in glial populations are unknown, it has been suggested that increased neuronal size and coinciding metabolic demand explains the need for increased glial support [2,3]. Indeed, cortical regions show increased glia: neuron ratios across animal species, suggesting that glia may be of evolutionary importance. Similarly, using a combination of glial fibrillary acidic protein (GFAP) and S100 calcium binding protein B (S100B), markers primarily expressed in astrocytes, at least nine different astrocyte populations may be identified that are phenotypically diverse, but region specific to the extent that they may be used to delineate different anatomical regions in the brain . The unique morphology and excitability of astrocytes allows them to taken on several structural functions in the CNS that include maintenance of the blood brain barrier, ion homeostasis, and regulation of neuron-neuron communication . This heterogeneity gives a level of versatility to the astrocyte that allows it to have profound effects on the surrounding neuronal network. A novel study recently published supports the potential evolutionary role of astrocytes in promoting cognitive ability. Using cultured human glial progenitor cells engrafted into neonatal mice, Han et al . exhibited that these glial progenitors differentiate to Pramipexole dihydrochloride become astrocytes and show enhanced function. These glia differentiated into mature astrocytes, integrated into the Rabbit Polyclonal to AKAP2 existing host astroglial network, exhibited faster propagation of Ca2+ signaling, and promoted LTP. Furthermore, these human glia chimeric mice exhibited increased cognitive ability as exhibited by improved performance in the Barnes maze, object-location tasks, alongside contextual and tone fear conditioning tasks . These studies support the notion that astrocytes are heterogeneous elements contributing to cognitive function, either through homeostatic maintenance or other mechanisms. Anatomically, astroglial are stereotypically identified by their Pramipexole dihydrochloride star-shaped morphology. However, as mentioned above, they also exhibit substantial heterogeneity that may explain their expansive functions Pramipexole dihydrochloride within the nervous system . While astrocytes may be classified based on morphology, this can often be difficult due to their wide variation in appearance. Thus, the most widely used methods of identifying astrocytes are the molecular marker, GFAP and Pramipexole dihydrochloride S100B [8,9]. Both markers have been shown to be sensitive to the major astrocyte types, protoplasmic and fibrous . Protoplasmic astrocytes are commonly found in grey matter and are characterized by their fine, almost cloudlike, processes enveloping neuronal synapses. Fibrous astrocytes, found in white matter, differ in that they exhibit thin and defined processes which are unbranched and whose end-feet meet neuronal nodes of Ranvier. While the aforementioned markers and morphologic phenotypes are useful for broad characterization of astrocytes, other classes of astroglia exist. ASTROCYTES AND COMMUNICATION Calcium Waves and Astrocyte Excitability Astrocytes had long been considered passive members of the CNS without electrical activity. It wasnt until the 1990s when new techniques in Ca2+ imaging revealed them as excitable, albeit in ways different from the neuron. The earliest studies exhibited how cultured hippocampal astrocytes responded to glutamate with increases in intracellular calcium , or that mechanical stimulation of a single astrocyte in a primary glial culture could increase intracellular calcium concentration . In both instances, specific increases in intracellular calcium were propagated to cells in the surrounding cultures providing us with some of the earliest evidence of communication between astrocytes. Gap junctions between local astrocytes in addition to extracellular adenosine triphosphate (ATP) link this activity to the surrounding glia and onward in.