Astroglial cradle in the life of the synapse

Abstract

Astroglial perisynaptic sheath covers the majority of synapses in the central nervous system. This glial coverage evolved as a part of the synaptic structure in which elements directly responsible for neurotransmission (exocytotic machinery and appropriate receptors) concentrate in neuronal membranes, whereas multiple molecules imperative for homeostatic maintenance of the synapse (transporters for neurotransmitters, ions, amino acids, etc.) are shifted to glial membranes that have substantially larger surface area. The astrocytic perisynaptic processes act as an 'astroglial cradle' essential for synaptogenesis, maturation, isolation and maintenance of synapses, representing the fundamental mechanism contributing to synaptic connectivity, synaptic plasticity and information processing in the nervous system. Multiple components of the central synapseThe power of the brain lies in the intercellular connections; some tens of trillions of these connections create the neural web that is the substrate for information processing. The connectivity of neural networks is immensely plastic and it is constantly remodelled under the influence of the environment and experience; this remarkable plasticity underlies learning. Intercellular connections in the nervous system are represented by chemical and electrical synapses, with the former predominantly established between neurons and the latter between neuroglia. Chemical transmission in the brain is not confined to synapses, it also operates in a 'volume transmission' mode when neurotransmitters diffuse through interstitial space, finding their multiple targets between neurons and neuroglial cells.Synaptic structures evolved over the last approximately 600 million years, after the first diffuse nervous system appeared in primitive animals such as hydras and comb jellies; this first nervous system was composed from cells of a single cell type, the neurons, which establish a neuronal net through synaptic contacts. Subsequent evolution of the nervous system progressed by the way of great diversification and specialization of cells. The first glial-like cells emerged in nematodes, they became specialized in annelids and attained a high degree of morphological and functional heterogeneity in arthropods. In basal chordates, the new type of glial cells, the radial glia, replaced parenchymal glial cells, which signalled an advent of layered organization of the central nervous system (CNS). Increase in the size of the CNS instigated re-emergence and diversification of astrocytes and appearance of myelin [1]. The brain and the spinal cord of mammals contain hundreds of distinct types of neurons and many types of neuroglia. Similarly, there are many types of synapses established between neuronal terminals and effector organs in the periphery or between neuronal terminals and other neurons and between neurons and some NG2 glial cells [2] in the CNS as well as in sympathetic ganglia or enteric plexuses.Synapses in the CNS are composed of several distinct components (figure 1), which incl...

Astroglial calcium signalling in Alzheimer's disease

“…Atrophy of astroglial perisynaptic processes, which foster and maintain synaptic transmission (as embellished by the concept of the astroglial cradle - [109]) can be an important (if not the leading) mechanism of synaptic weakening and synaptic loss that signals the beginning of AD pathology [110]. General decrease in the astroglial homeostatic reserve reduces neuroprotection and may be detrimental for the neuro-vascular unit and may affect the glial ability to metabolically support neuronal networks.…”

The Special Case of Human Astrocytes

“…Some argued that glia existed merely to fill the otherwise empty spaces and provide a structural matrix, within which neurones are embedded [9], whereas some, however, went much further and assigned glia fundamental homeostatic functions [25] , whilst still others, most notably Carl Ludwig Schleich and Santiago Ramón y Cajal, suggested that glial cells control local blood flow, initiate sleep, and regulate information transfer in neuronal networks [8,14,26]. It is now apparent that astrocytes fulfil all of these operations and more, including the most fundamental neuronal attribute of synaptogenesis [27][28][29][30]. Similarly, the fundamental role of neuroglia in neurological diseases was highlighted by the most prominent neuropathologists, such as Franz Nissl, Carl Frommann, Ludwig Merzbacher, Alois Alzheimer, and Nicolas Achucarro [13,[31][32][33][34].…”

Astrocyte-Synapse Receptor Coupling in Tripartite Synapses: A Mechanism for Self-Observing Robots

“…They subdivide progressively to form finer and finer processes of up to 100.000 per astrocyte. Most of these processes interact with synapses, termed perisynaptic astrocytic processes (PSAPs) [19]. Fewer processes contact vessels, called perivascular astrocytic processes (PVAPs) [20].…”