Close apposition of neurones and astroglia the tripartite synapse

In the grey matter, astrocytes are closely associated with neuronal membranes and specifically with synaptic regions, so that in many cases astroglial membranes completely or partially enwrap presynaptic terminals as well as postsynaptic structures. In the hippocampus, for example, ~60 per cent of all axon-dendritic synapses are surrounded by astroglial membranes. These astrocyte-synapse contacts show peculiar specificity: astroglial membranes enwrap about 80 per cent of large perforated synapses (which are probably the most functionally active), whereas only about half of small (known as macular) synapses are covered by glial membranes. In the cerebellum, glial-synaptic relations are even more intimate, as nearly all of the synapses formed by parallel fibres on the dendrites of Purkinje neurone are covered by the membranes of Bergmann glial cells; each individual Bergmann cell enwraps between 2000 and 6000 synaptic contacts. The terminal strictures of astrocytes, which cover the synaptic regions, have a rather complex morphology: the Bergmann glial cells, for example, send specialized appendages, which cover several synapses and form a relatively independent compartment (Figure 6.1). This cover is quite intimate as the distance between glial membranes and synaptic structures in cerebellum and hippocampus is as close as 1 ^m. The very intimate morphological apposition of astrocytes and synaptic structures allow the former to be exposed to the neurotransmitters released from the synaptic terminals. Functionally, the processes of astroglial cells are endowed with neurotransmitter receptors, and most importantly, the modalities of receptors expressed by astroglial membranes precisely match the neurotransmitters released at the synapses they cover. In this respect, astrocytes in fact have a complement of receptors very similar to that of their neuronal neighbour. In the cerebellum, for example, the Purkinje neurone/Bergmann glia pair receives several synaptic inputs, which use as neurotransmitters glutamate, ATP, noradrenalin, histamine and GABA; both neurone and glial cell express receptors specific for these substances (see Chapter 5). In the cortex, both pyramidal neurones and neighbouring astroglial

Glial Neurobiology: A Textbook Alexei Verkhratsky and Arthur Butt © 2007 John Wiley & Sons, Ltd ISBN 978-0-470-01564-3 (HB); 978-0-470-51740-6 (PB)

Tripartite Synapse

Figure 6.1 Close morphological contacts between Bergmann glial cells and Purkinje neurones in cerebellum. Left panel shows a three-dimensional reconstruction of an appendage extending from the process of the Bergmann glial cell. Electron micrographs of four sections contributing to the reconstruction (designated 1-4) are shown on the right; glial compartments appear black (from the injected dye). The location of these sections in the reconstruction is indicated by the labelled arrows. (1) Region directly contacting synapses. (2) Glial compartments without direct synaptic contacts. (3) Bulging glial structure containing a mitochondrion. (4) The stalk of the appendage. Note how completely the glial membranes enwrap the synaptic terminal in panel (1). (Modified from Grosche J, Matyash V, Moller T, Verkhratsky A, Reichenbach A, Kettenmann H (1999) Microdomains for neuron-glia interaction: parallel fiber signaling to Bergmann glial cells. Nat Neurosci 2, 139-143)

Figure 6.1 Close morphological contacts between Bergmann glial cells and Purkinje neurones in cerebellum. Left panel shows a three-dimensional reconstruction of an appendage extending from the process of the Bergmann glial cell. Electron micrographs of four sections contributing to the reconstruction (designated 1-4) are shown on the right; glial compartments appear black (from the injected dye). The location of these sections in the reconstruction is indicated by the labelled arrows. (1) Region directly contacting synapses. (2) Glial compartments without direct synaptic contacts. (3) Bulging glial structure containing a mitochondrion. (4) The stalk of the appendage. Note how completely the glial membranes enwrap the synaptic terminal in panel (1). (Modified from Grosche J, Matyash V, Moller T, Verkhratsky A, Reichenbach A, Kettenmann H (1999) Microdomains for neuron-glia interaction: parallel fiber signaling to Bergmann glial cells. Nat Neurosci 2, 139-143)

cells express glutamate and purinoreceptors, whereas in the basal ganglia neurones and astrocytes are sensitive to dopamine. In the ability to sense neurotransmitter release, therefore, the astroglial cell closely resembles the postsynaptic neurone.

The close morphological relations between astrocytes and synapses as well as functional expression of relevant receptors in the astroglial cells prompted the appearance of a new concept of synaptic organization known as the 'tripartite synapse'. According to this concept, synapses are built from three equally important parts, the presynaptic terminal, the postsynaptic neuronal membrane and the surrounding astrocyte (Figure 6.2). Neurotransmitter released from the presynaptic terminal activates receptors in both the postsynaptic neuronal membrane and the perisynaptic astroglial membranes. This results in the generation of a postsynaptic potential in the neurone and a Ca2+ signal in the astrocyte. The latter may prop-

Presynaptic terminal

Presynaptic terminal

Tripartite Neurone

Figure 6.2 The tripartite synapse. The concept of the tripartite synapse assumes that it is constructed from a presynaptic terminal, the postsynaptic neuronal membrane, and surrounding astrocyte processes. The neurotransmitter released from the presynaptic terminal interacts with specific receptors located in both the postsynaptic neuronal membrane and in the astroglial membrane. Astrocytes may signal back to neurones by releasing 'gliotransmitters'

Figure 6.2 The tripartite synapse. The concept of the tripartite synapse assumes that it is constructed from a presynaptic terminal, the postsynaptic neuronal membrane, and surrounding astrocyte processes. The neurotransmitter released from the presynaptic terminal interacts with specific receptors located in both the postsynaptic neuronal membrane and in the astroglial membrane. Astrocytes may signal back to neurones by releasing 'gliotransmitters'

agate through the astroglial cell body or through astrocytic syncytium; this Ca2+ signal may also trigger release of 'glio' transmitters from astrocytes, which in turn will signal onto both pre- and postsynaptic neuronal membrane.

This concept of the tripartite synapse, which predicts bi-directional neuronal glial communication, has received strong experimental support, as both neurone-to-glia and glia-to-neurone signalling can be observed in the nervous system.

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  • aman
    How do CNS drugs bind to receptors in postsynaptic cells?
    5 years ago

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