Astrocyte Calcium Signal and Gliotransmission in Human Brain Tissue

Abstract

Brain function is recognized to rely on neuronal activity and signaling processes between neurons, whereas astrocytes are generally considered to play supportive roles for proper neuronal function. However, accumulating evidence indicates that astrocytes sense and control neuronal and synaptic activity, indicating that neuron and astrocytes reciprocally communicate. While this evidence has been obtained in experimental animal models, whether this bidirectional signaling between astrocytes and neurons occurs in human brain remains unknown. We have investigated the existence of astrocyte-neuron communication in human brain tissue, using electrophysiological and Ca(2+) imaging techniques in slices of the cortex and hippocampus obtained from biopsies from epileptic patients. Cortical and hippocampal human astrocytes displayed spontaneous Ca(2+) elevations that were independent of neuronal activity. Local application of transmitter receptor agonists or nerve electrical stimulation transiently elevated Ca(2+) in astrocytes, indicating that human astrocytes detect synaptic activity and respond to synaptically released neurotransmitters, suggesting the existence of neuron-to-astrocyte communication in human brain tissue. Electrophysiological recordings in neurons revealed the presence of slow inward currents (SICs) mediated by NMDA receptor activation. The frequency of SICs increased after local application of ATP that elevated astrocyte Ca(2+). Therefore, human astrocytes are able to release the gliotransmitter glutamate, which affect neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of reciprocal signaling between neurons and astrocytes in human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in human brain function.

Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

“…Transport of neurotransmitters and glucose by astrocytes governs the composition of the extracellular space surrounding neurons, thus directly influencing neuronal electrical activity and glucose-sensing capacity (30,59,60), both of which are affected by early changes in nutritional status. Glial coverage of POMC neurons in the arcuate nucleus was increased in offspring of mothers fed a HFD, and this was associated with a decrease in miniature inhibitory postsynaptic current (mIPSC) frequency.…”

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

“…In brief, the foundation of bidirectional communication is that astrocytes both respond to (Porter and McCarthy, 1996) and release (Parpura et al, 1994) transmitter, which ultimately impacts synaptic plasticity and behavior (Parpura et al, 2012). Additionally, bidirectional communication was also recently observed in human brain preparations (Navarrete et al, 2013). Increased [Ca þþ ] i is both necessary and sufficient for most forms of astrocytic transmitter release (Parpura et al, 1994).…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…Human and rodent astrocytes also differ with regards to their transcripts (Miller et al, 2010) as do in fact astrocytes from different brain regions (Doyle et al, 2008; Rodriguez et al, 2014; Yeh et al, 2009). Nonetheless, experiments in acute slices from the human cortex and hippocampus have documented astroglial Ca 2+ signals in response to excitatory afferent stimulation or application of glutamate, cannabinoid, and purinergic receptor agonists (Navarrete et al, 2013). Furthermore, the gene expression patterns for major glutamate transporters and several subtypes of mGluRs appear generally compatible between human and mouse adult brain astrocytes (Sun et al, 2013).…”