Astrocyte Regulation of Synaptic Behavior

Abstract

Astrocytes regulate multiple aspects of neuronal and synaptic function from development through to adulthood. Instead of addressing each function independently, this review provides a comprehensive overview of the different ways astrocytes modulate neuronal synaptic function throughout life, with a particular focus on recent findings in each area. It includes the emerging functions of astrocytes, such as a role in synapse formation, as well as more established roles, including the uptake and recycling of neurotransmitters. This broad approach covers the many ways astrocytes and neurons constantly interact to maintain the correct functioning of the brain. It is important to consider all of these diverse functions of astrocytes when investigating how astrocyte-neuron interactions regulate synaptic behavior to appreciate the complexity of these ongoing interactions.

Glia in mammalian development and disease

“…Work over the past decade has overwhelmingly demonstrated that astrocytes, which were once thought to function only as supporting cells for neurons, play diverse and essential regulatory roles in the developing and adult CNS (reviewed by Allen, 2014). Astrocytes are the most abundant cell type in the vertebrate CNS, and are classified as protoplasmic (gray matter) or fibrous (white matter).…”

“…More recently, it has become apparent that astrocytes also powerfully control the formation, strength and turnover of synapses. Since the first demonstrations nearly two decades ago that astrocytes are required for the formation of functional synapses in retinal ganglion cells, there has been great progress in identifying the numerous proteins released by astrocytes that control excitatory synapse formation and function (reviewed by Clarke and Barres, 2013;Allen, 2014). These include astrocytesecreted proteins that trigger the formation of postsynaptically silent synapses (e.g.…”

“…Synapse remodeling refers to the elimination (or 'pruning') of unnecessary synapses and the strengthening of remaining synapses. Extensive work in the last decade has revealed that both microglia and astrocytes are essential players in the elimination of CNS synapses during development, and that Schwann cells eliminate excess axons and synapses in the developing PNS (Allen, 2014;Schafer and Stevens, 2015). Importantly, in all cases, synapse elimination by glia has been found to be activity dependent; that is, weak synapses are selectively pruned, and strong synapses are spared.…”

Functioning of Circuits Connecting Thalamus and Cortex

“…The functional significance of this is unclear, but to the extent that glial sheaths control transmitter availability [e.g., (3,118)], such a process would be absent in glomeruli. A final point is that synapses from interneuronal axons are also often found in glomeruli, but these make conventional, simple synapses, unlike their dendritic counterparts.…”

“…Much of this has to do with the modulator properties of this pathway and its ability to activate metabotropic glutamate receptors. At least four independent sites of action of the pathway have so far been demonstrated, and these are outlined in Figure 9 [1] The IPSP activated indirectly in thalamic relay cells via the local GABAergic cells tends to be larger than and can swamp the direct EPSP (85); [2] cortical activation of presynaptic metabotropic glutamate receptors on retinal terminals reduces transmitter release and thus the gain of retinogeniculate transmission (51,86); [3] layer 6 input onto thalamocortical target cells in layer 4 often produces sustained hyperpolarization through activation of postsynaptic group II metabotropic glutamate receptors (90); and [4] layer 6 input to layer 4 cells activates metabotropic glutamate receptors presynaptically on thalamocortical terminals to reduce transmitter release and down regulate thalamocortical EPSPs (92). Note that each of these actions would result in a reduction of the gain of thalamocortical transmission, and in this regard, it is more consistent with the recent demonstration that reaches a similar conclusion from optogenetic control of the pathway (115).…”