ABSTRACT
Aging, Alzheimer’s disease and many degenerative diseases are accompanied by serious cognitive deficits, particularly impaired learning and memory loss. This decline in old age is a consequence of changes in brain anatomy, morphology and volume and functional deficits. Nervous tissue, particularly in the hippocampus and cortex, is subject to various degenerative processes including a decreased number and efficacy of synapses, a decrease in transmitter release, neuronal loss, astrogliosis, changes in astrocytic morphology, demyelination, deposits of β-amyloid and changes in extracellular matrix proteins1-4. These and other changes affect not only the efficacy of signal transmission at synapses, but also the functioning of glia and extrasynaptic (Volume’) transmission mediated by the diffusion of transmitters as well as other substances through the volume of the extracellular space (ECS)5-10. This mode of communication without synapses provides a mechanism of long-range information processing in functions such as vigilance, sleep, chronic pain, hunger, depression, long-term potentiation (LTP), longterm depression (LTD), memory formation and other plastic changes in the central nervous system (CNS)7,11,12.
