Anales RANF

P.54 ROLE OF ASTROCYTIC ADENOSINE A 2A RECEPTORS IN THE FACILITATION OF SYNAPTIC PLASTICITY IN CORTICO- STRIATAL SYNAPSES D. Rial 1,2 , N. Gonçalves 1 , F. Queiroz 1 , H.B. Silva 1 , S. Schiffmann 2 , J.F Chen 3 , A. Tomé 1 , R.A. Cunha 1 . 1 University of Coimbra, Coimbra, Portugal; 2 Université Libre de Bruxelles (ULB), Brussels, Belgium; 3 Boston University, Boston, USA. Adenosine A 2A receptors (A 2A R) control numerous striatal functions (locomotion, habits, addiction). A 2A R are mainly located in striatal medium spiny neurons (MSN), which are driven by cortical glutamatergic projection and modulated by dopaminergic inputs. We now tested if and how A 2A R control cortico-striatal plasticity, by comparing the amplitude of long-term potentiation (LTP) in cortico-striatal slices (% basal), in the absence and in the presence of the selective A 2A R antagonist, SCH58261 (50 nM) in 4 mouse lines: wild type (WT), global A 2A R knockout (g-KO), striatum-A 2A R-KO (st-KO with selective A 2A R elimination in MSNs) and forebrain-A 2A R-KO mice (fb-KO, with A 2A R elimination in glutamatergic and GABAergic neurons). In WT, LTP amplitude was 127+4% and SCH58261 inhibited LTP by -57±4% (n=4). To gauge the cellular site of action of A 2A R, we found that the effect of SCH58261 (n=4) on LTP was: 1-blunted in g-KO; 2-preserved in st-KO (-58±5%); 3-attenuated in fb-KO (-24±7%); 4-attenuated in WT mice injected in the pre-motor cortex with lentivirus expressing an sh-RNA to down-regulate A 2A R in glutamatergic terminals (-18±1%). Atropine (1 µ M) did not affect the effect of SCH58261 on LTP (-6±4%, n=4), excluding the involvement of cholinergic modulation. Notably, the blockade of astrocytic glutamate uptake with DL- TBOA (50 µ M) attenuated the effect of SCH58261 on LTP (-24±12%, n=4) in WT and blunted the effect of SCH58261 in fb-KO (n=4). This prompts the novel hypothesis that astrocytic A 2A R play a prominent role in the control of cortico-striatal plasticity. Support: Fundacion LaCaixa, CENTRO-01-0246-FEDER-000010 and FCT (PTDC/SAU-TOX/122005/2010, POCI-01-0145-FEDER-031274, DARPA (09-68- ESR-FP-010) and BELSPO.