Local Ca2+ detection and modulation of synaptic release by astrocytes

Abstract

Astrocytes communicate with synapses by means of intracellular calcium ([Ca(2+)](i)) elevations, but local calcium dynamics in astrocytic processes have never been thoroughly investigated. By taking advantage of high-resolution two-photon microscopy, we identify the characteristics of local astrocyte calcium activity in the adult mouse hippocampus. Astrocytic processes showed intense activity, triggered by physiological transmission at neighboring synapses. They encoded synchronous synaptic events generated by sparse action potentials into robust regional (∼12 μm) [Ca(2+)](i) elevations. Unexpectedly, they also sensed spontaneous synaptic events, producing highly confined (∼4 μm), fast (millisecond-scale) miniature Ca(2+) responses. This Ca(2+) activity in astrocytic processes is generated through GTP- and inositol-1,4,5-trisphosphate-dependent signaling and is relevant for basal synaptic function. Thus, buffering astrocyte [Ca(2+)](i) or blocking a receptor mediating local astrocyte Ca(2+) signals decreased synaptic transmission reliability in minimal stimulation experiments. These data provide direct evidence that astrocytes are integrated in local synaptic functioning in adult brain.

Rapid stimulus-evoked astrocyte Ca 2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo

“…The majority of the fast, high-frequency signals could be identified only after superposition of data points recorded during a stimulation train, which might explain why fast astrocytic Ca 2+ signals have so seldom been reported in vivo (9) and emphasizes the relevance of the method of analysis applied here. Our results are consistent with work in hippocampal slices (16,17). In somatosensory cortex, previous findings suggested that only 5% of astrocyte somas had fast Ca 2+ responses in vivo (9).…”

“…Furthermore, uncaging of Ca 2+ in astrocytes triggers vascular responses in brain slices through specific Ca 2+ -dependent pathways with a protracted time course (14, 15). More recently, stimulation of single presynaptic neurons in hippocampal slices was shown to evoke fast, brief, local Ca 2+ elevations in astrocytic processes that were essential for local synaptic functioning in the adult brain (16,17). This work prompted us to reexamine the characteristics of fast, brief astrocytic Ca 2+ signals in vivo with special regard to neurovascular coupling, i.e., the association between local increases in neural activity and the concomitant rise in local blood flow, which constitutes the physiological basis for functional neuroimaging.…”

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

“…Ca 2+ signals can trigger the release of gliotransmitters (glutamate, D-serine, ATP), which in turn regulate synaptic transmission [2]. Through these mechanisms, astrocytes have been proposed to play a critical role in modulating synaptic transmission [9,10], plasticity properties [11][12][13], and longterm potentiation (LTP) [14], consistent with evidence suggesting that astrocytic Ca 2+ transients can occur in spatially restricted areas [15,16]. However, other studies have also proposed different mechanisms to account for a contribution of astrocytes to plasticity and memory [17,18].…”

Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation

“…Ip3r2 mice were maintained as a heterozygous line and genotypes were determined using previously reported mutant allele-specific primers (Li et al 2005). Female C57BL/6J (Charles River) or Ip3r2 -/-mice with wild-type littermates (Ip3r2 +/+ ; Li et al 2005;Di Castro et al 2011) were surgically prepared at eight to ten weeks of age.…”