Layer-Specific Noradrenergic Modulation of Inhibition in Cortical Layer II/III

Abstract

Norepinephrine (NE) is released in the neocortex after activation of the locus coeruleus of the brain stem in response to novel, salient, or fight-or-flight stimuli. The role of adrenergic modulation in sensory cortices is not completely understood. We investigated the possibility that NE modifies the balance of inhibition acting on 2 different γ-aminobutyric acid (GABA)ergic pathways. Using patch-clamp recordings, we found that the application of NE induces an α(1) adrenergic receptor-mediated decrease of the amplitude of inhibitory postsynaptic currents (IPSCs) evoked by stimulation of layer I (LI-eIPSCs) and a β and α(2) receptor-mediated increase in the amplitude of IPSCs evoked by stimulation of layer II/III (LII/III-eIPSCs). Analysis of minimal stimulation IPSCs, IPSC kinetics, and sensitivity to the GABA(A) receptor subunit-selective enhancer zolpidem corroborated the functional difference between LI- and LII/III-eIPSCs, suggestive of a distal versus somatic origin of LI- and LII/III-eIPSCs, respectively. These findings suggest that NE shifts the balance between distal and somatic inhibition to the advantage of the latter. We speculate that such shift modifies the balance of sensory-specific and emotional information in the integration of neural input to the upper layers of the auditory cortex.