Three-Dimensional Relationships between Hippocampal Synapses and Astrocytes

Abstract

Recent studies show that glutamate transporter-mediated currents occur in astrocytes when glutamate is released from hippocampal synapses. These transporters remove excess glutamate from the extracellular space, thereby facilitating synaptic input specificity and preventing neurotoxicity. Little is known about the position of astrocytic processes at hippocampal synapses. Serial electron microscopy and three-dimensional analyses were used to investigate structural relationships between astrocytes and synapses in stratum radiatum of hippocampal area CA1 in the mature rat in vivo and in slices. Only 57 +/- 11% of the synapses had astrocytic processes apposed to them. Of these, the astrocytic processes surrounded less than half (0.43 +/- 22) of the synaptic interface. Other studies suggest that astrocytes extend processes toward higher concentrations of glutamate; thus the presence of astrocytic processes at particular hippocampal synapses might signal which ones are releasing glutamate. The distance between nearest neighboring synapses was usually (approximately 95%) <1 microgram. Astrocytic processes occurred along the extracellular path between 33% of the neighboring synapses, neuronal processes occurred along the path between another 66% of the neighboring synapses, and only 1% of the synapses were close enough such that neither astrocytic nor neuronal processes occurred between them. These morphological arrangements suggest that the glutamate released at approximately two-thirds of hippocampal synapses might diffuse to other synapses, unless neuronal glutamate transporters are more effective than previously reported. The findings also suggest that physiological recordings made from hippocampal astrocytes do not uniformly sample the glutamate released from all hippocampal synapses.

Glycine Uptake Regulates Hippocampal Network Activity via Glycine Receptor-Mediated Tonic Inhibition

“…Glia has been shown to contain B2 mM glycine (Berger et al, 1977), which enables glia to participate in the control of glycine concentration. Furthermore, two-thirds of the axon-dendritic spines in CA1 region are associated with astrocytic processes (Ventura and Harris, 1999), suggesting a wide distribution and close colocalization of glial cells with neurons. In fact, potassium can stimulate the spontaneous release of glycine from astrocytes through a Ca 2 + -independent mechanism (Holopainen and Kontro, 1989).…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…In the rat neocortex only 29 to 56% of excitatory synapses are enwrapped by astrocytic processes, with variable extent of the immediate contact (Bernardinelli et al, 2014a; Reichenbach et al, 2010). In contrast, in layer IV of the somatosensory cortex in adult mice 90% of spines are in contact with astrocytes (Bernardinelli et al, 2014a) whereas in the rat hippocampus this number is ∼62 to 90% (Ventura and Harris, 1999; Witcher et al, 2007). It appears that astrocytic processes approach preferentially synapses that have complex (e.g.…”

The adenosine kinase hypothesis of epileptogenesis

“…This manipulation led to the loss of the A 1 R mediated tonic inhibition in hippocampal slices (Pascual et al, 2005) indicating that under physiological conditions astrocytic release of ATP (and subsequent cleavage by ectonucleotidases) is a major source of extracellular adenosine. Since each astrocyte contacts thousands of synapses (Ventura and Harris, 1999), it is conceivable that astrocytic release of ATP has the function to set a global adenosine-mediated inhibitory tone within a neuronal network, while presynaptic release of ATP from neurons (see above) and its conversion to adenosine may have the function to selectively potentiate individual synaptic transmission within a globally inhibited network.…”