Ischemic-LTP in striatal spiny neurons of both direct and indirect pathway requires the activation of D1-like receptors and NO/soluble guanylate cyclase/cGMP transmission

Sara Arcangeli, Alessandro Tozzi, Michela Tantucci, Cristiano Spaccatini, Antonio De Iure, Cinzia Costa, Massimiliano Di Filippo, Barbara Picconi, Carmen Giampà, Francesca Romana Fusco, Salvatore Amoroso, Paolo Calabresi

Research output: Contribution to journalArticlepeer-review

Abstract

Striatal medium-sized spiny neurons (MSNs) are highly vulnerable to ischemia. A brief ischemic insult, produced by oxygen and glucose deprivation (OGD), can induce ischemic long-term potentiation (i-LTP) of corticostriatal excitatory postsynaptic response. Since nitric oxide (NO) is involved in the pathophysiology of brain ischemia and the dopamine D1/D5-receptors (D1-like-R) are expressed in striatal NOS-positive interneurons, we hypothesized a relation between NOS-positive interneurons and striatal i-LTP, involving D1R activation and NO production. We investigated the mechanisms involved in i-LTP induced by OGD in corticostriatal slices and found that the D1-like-R antagonist SCH-23390 prevented i-LTP in all recorded MSNs. Immunofluorescence analysis confirmed the induction of i-LTP in both substance P-positive, (putative D1R-expressing) and adenosine A2A-receptor-positive (putative D2R-expressing) MSNs. Furthermore, i-LTP was dependent on a NOS/cGMP pathway since pharmacological blockade of NOS, guanylate-cyclase, or PKG prevented i-LTP. However, these compounds failed to prevent i-LTP in the presence of a NO donor or cGMP analog, respectively. Interestingly, the D1-like-R antagonism failed to prevent i-LTP when intracellular cGMP was pharmacologically increased. We propose that NO, produced by striatal NOS-positive interneurons via the stimulation of D1-like-R located on these cells, is critical for i-LTP induction in the entire population of MSNs involving a cGMP-dependent pathway.

Original languageEnglish
Pages (from-to)278-286
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume33
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • D1 dopamine receptor
  • in vitro ischemia
  • ischemic-LTP
  • nitric oxide
  • NOS-positive interneuron

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

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