TY - JOUR
T1 - Extracellular Ca 2+ acts as a mediator of communication from neurons to glia
AU - Torres, Arnulfo
AU - Wang, Fushun
AU - Xu, Qiwu
AU - Fujita, Takumi
AU - Dobrowolski, Radoslaw
AU - Willecke, Klaus
AU - Takano, Takahiro
AU - Nedergaard, Maiken
PY - 2012/1/24
Y1 - 2012/1/24
N2 - Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca 2+] e) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca 2+buffer diazo-2 {N-[2-[2-[2- [bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl] -N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca 2+] e or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca 2+ triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca 2+ signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in [Ca 2+] e may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability.
AB - Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca 2+] e) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca 2+buffer diazo-2 {N-[2-[2-[2- [bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl] -N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca 2+] e or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca 2+ triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca 2+ signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in [Ca 2+] e may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability.
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U2 - 10.1126/scisignal.2002160
DO - 10.1126/scisignal.2002160
M3 - Article
C2 - 22275221
AN - SCOPUS:84863036116
VL - 5
JO - Science's STKE : signal transduction knowledge environment
JF - Science's STKE : signal transduction knowledge environment
SN - 1937-9145
IS - 208
ER -