title: 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.
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.
authors.affiliation: Clinica Neurologica, Università di Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Arcangeli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tozzi
authors.forename: Michela
authors.initials: M
authors.lastname: Tantucci
authors.forename: Cristiano
authors.initials: C
authors.lastname: Spaccatini
authors.forename: Antonio
authors.initials: A
authors.lastname: de Iure
authors.forename: Cinzia
authors.initials: C
authors.lastname: Costa
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Filippo
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.forename: Carmen
authors.initials: C
authors.lastname: Giampà
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Fusco
authors.forename: Salvatore
authors.initials: S
authors.lastname: Amoroso
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D006152:Cyclic GMP / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050641:Receptors, Dopamine D5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D001552:Benzazepines; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D050641:Receptors, Dopamine D5; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D005947:Glucose; D010100:Oxygen