Noradrenaline Increases mEPSC Frequency in Pyramidal Cells in Layer II of Rat Barrel Cortex via Calcium Release From Presynaptic Stores

Somatosensory cortex is innervated by afferents originating from the locus coeruleus which typically release noradrenaline. We tested if activation of presynaptic α(1)-adrenoceptors (AR) coupled to a G(q)-mediated signaling cascade resulted in calcium (Ca(2+)) release from stores and thereby increased spontaneous transmitter release in rat barrel cortex. Adding 1–100 μM noradrenaline (NA) or 5 μM cirazoline (CO), a α(1)-AR specific agonist, to the standard artificial cerebrospinal fluid increased the frequency of miniature excitatory postsynaptic currents (mEPSC) by 64 ± 7% in 51% of pyramidal cells in layer II (responders) with no effect on the amplitude. In 42 responders, the mEPSC frequency during control was significantly smaller (39 ± 2 vs. 53 ± 4 Hz) and upon NA exposure, the input resistance (R(in)) decreased (9 ± 7%) compared to non-responders. Experiments using CO and the antagonist prazosin revealed that NA acted via binding to α(1)-ARs, which was further corroborated by simultaneously blocking β- and α(2)-ARs with propranolol and yohimbine, which did not prevent the increase in mEPSC frequency. To verify elements in the signaling cascade, both the phospholipase C inhibitor edelfosine and the membrane permeable IP(3) receptor blocker 2-APB averted the increase in mEPSC frequency. Likewise, emptying Ca(2+) stores with cyclopiazonic acid or the chelation of intracellular Ca(2+) with BAPTA-AM prevented the frequency increase, suggesting that the frequency increase was caused by presynaptic store release. When group I metabotropic glutamate receptors were activated with DHPG, co-application of NA occluded a further frequency increase suggesting that the two receptor activations may not signal independently of each other. The increased mEPSC frequency in a subset of pyramidal cells results in enhanced synaptic noise, which, together with the reduction in R(in), will affect computation in the network.