NPY signaling through Y1 receptors modulates thalamic oscillations

Neuropeptide Y is the ligand of a family of G-protein coupled receptors (Y(1) to Y(6)). In the thalamus, exogenous and endogenously released NPY can shorten the duration of thalamic oscillations in brain slices from P13 to P15 rats, an in vitro model of absence seizures. Here, we examine which Y receptors are involved in this modulation. Application of the Y(1) receptor agonist Leu(31)Pro(34)NPY caused a reversible reduction in the duration of thalamic oscillations (-26.6+/-7.8%), while the Y(2) receptor agonist peptideYY((3-36)) and the Y(5) receptor agonist BWX-46 did not exert a significant effect. No Y receptor agonist affected oscillation period. Application of antagonists of Y(1), Y(2) and Y(5) receptors (BIBP3226, BIIE0246 and L152,806, respectively) produced results consistent with those obtained from agonists. BIBP3226 caused a reversible disinhibition, an effect that increases oscillation duration (18.2+/-9.7%) while BIIE0246 and L152,806 had no significant effect. Expression of NPY is limited to neurons in the reticular thalamic nucleus (nRt), but Y(1) receptors are expressed in both nRt and adjacent thalamic relay nuclei. Thus, intra-nRt or nRt to relay nucleus NPY release could cause Y(1) receptor mediated inhibition of thalamic oscillations.