title: Calcium signals in the nucleus accumbens: activation of astrocytes by ATP and succinate.
abstract: BACKGROUND
  Accumulating evidence suggests that glial signalling is activated by different brain functions. However, knowledge regarding molecular mechanisms of activation or their relation to neuronal activity is limited. The purpose of the present study is to identify the characteristics of ATP-evoked glial signalling in the brain reward area, the nucleus accumbens (NAc), and thereby to explore the action of citric acid cycle intermediate succinate (SUC).
  
  
  RESULTS
  We described the burst-like propagation of Ca2+ transients evoked by ATP in acute NAc slices from rat brain. Co-localization of the ATP-evoked Ca2+ signalling with immunoreactivities of the astroglia-specific gap junction forming channel protein connexin43 (Cx43) and the glial fibrillary acidic protein (GFAP) indicated that the responsive cells were a subpopulation of Cx43 and GFAP immunoreactive astrocytes. The ATP-evoked Ca2+ transients were present under the blockade of neuronal activity, but were inhibited by Ca2+ store depletion and antagonism of the G protein coupled purinergic P2Y1 receptor subtype-specific antagonist MRS2179. Similarly, Ca2+ transients evoked by the P2Y1 receptor subtype-specific agonist 2-(Methylthio)adenosine 5'-diphosphate were also blocked by MRS2179. These characteristics implied that intercellular Ca2+ signalling originated from the release of Ca2+ from internal stores, triggered by the activation of P2Y1 receptors. Inhibition by the gap junction blockers carbenoxolone and flufenamic acid and by an antibody raised against the gating-associated segment of Cx43 suggested that intercellular Ca2+ signalling proceeded through gap junctions. We demonstrated for the first time that extracellular SUC also evoked Ca2+ transients (EC50 = 50-60 μM) in about 15% of the ATP-responsive NAc astrocytes. By contrast to glial cells, electrophysiologically identified NAc neurons surrounded by ATP-responsive astrocytes were not activated simultaneously.
  
  
  CONCLUSIONS
  We concluded, therefore, that ATP- and SUC-sensitive Ca2+ transients appear to represent a signalling layer independent of NAc neurons. This previously unrecognised glial action of SUC, a major cellular energy metabolite, may play a role in linking metabolism to Ca2+ signalling in astrocytic networks under physiological and pathological conditions such as exercise and metabolic diseases.
authors.affiliation: Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeriút 59-67, 1025 Budapest, Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Molnár
authors.forename: Arpád
authors.initials: A
authors.lastname: Dobolyi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nyitrai
authors.forename: Péter
authors.initials: P
authors.lastname: Barabás
authors.forename: László
authors.initials: L
authors.lastname: Héja
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Emri
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
authors.forename: Julianna
authors.initials: J
authors.lastname: Kardos
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002952:Citric Acid Cycle / Q000502:physiology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D019802:Succinic Acid / Q000494:pharmacology*
chemical_list: D000255:Adenosine Triphosphate; D019802:Succinic Acid