AUTHOR=Choy Julian M. C. , Agahari Fransiscus A. , Li Li , Stricker Christian 

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

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=12

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2018.00213

DOI=10.3389/fncel.2018.00213

ISSN=1662-5102

ABSTRACT=<p>Somatosensory cortex is innervated by afferents originating from the <italic>locus coeruleus</italic> which typically release noradrenaline. We tested if activation of presynaptic α<sub>1</sub>-adrenoceptors (AR) coupled to a G<sub>q</sub>-mediated signaling cascade resulted in calcium (Ca<sup>2+</sup>) 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<sub>1</sub>-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 <italic>vs.</italic> 53 ± 4 Hz) and upon NA exposure, the input resistance (<italic>R</italic><sub>in</sub>) decreased (9 ± 7%) compared to non-responders. Experiments using CO and the antagonist prazosin revealed that NA acted via binding to α<sub>1</sub>-ARs, which was further corroborated by simultaneously blocking β- and α<sub>2</sub>-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<sub>3</sub> receptor blocker 2-APB averted the increase in mEPSC frequency. Likewise, emptying Ca<sup>2+</sup> stores with cyclopiazonic acid or the chelation of intracellular Ca<sup>2+</sup> 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 <italic>R</italic><sub>in</sub>, will affect computation in the network.</p>