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Extracellular Environment of CNS Neurons - A.R. Gardner-Medwin Refs: From Neuron to Brain (Nicholls, Martin & Wallace) Chapters on glia and (in earlier editions) on extracellular environment. Sections on csf and blood-brain barrier in most textbooks. Learning Objectives: Understand mechanisms by which the composition of the micro-environment in the CNS is :(a) regulated in the long term by the blood-brain barrier (b) altered by neural activity in both normal and pathological situations (c) buffered in special circumstances by diffusion and glial function Understand how the size of the extracellular space has been measured experimentally, why it often comes to appear abnormally small in histological and EM pictures, and how it is altered by neurological and osmotic disturbances. Understand the relation between the cerebrospinal fluid (csf) and the microenvironment of the brain: parallel regulating mechanisms, bulk flow of fluid out of the brain (cf. lymphatic drainage in other systems), free but very slow diffusional equilibration. Understand the principal functions of the csf: reduced gravitational effects on the brain, lubrication, limited volume adjustment to cope with swelling, limited homeostasis. Understand why glial physiology was first studied in invertebrates, what special physiological membrane properties have been identified in glial cells (in vertebrates, particularly in astrocytes) and how these may play a role in short term homeostasis countering neurally induced disturbances of the micro-environment. Understand how the ionic composition of the micro-environment can be measured experimentally with ion-selective microelectrodes and how both these measurements and glial membrane potentials change during disturbances such as epilepsy, or even during normal physiological activity. Understand how positive feedback processes (such as K+ induced K+ release) can lead to severe dysfunction of neural tissue, as for example in the transient neural disorder called Spreading Cortical Depression (probably contributing to migraine), and how these effects may be countered by homeostatic buffering mechanisms, such as the K+ spatial buffer mechanism in glial cells.