title: Pre- and postsynaptic effects of norepinephrine on γ-aminobutyric acid-mediated synaptic transmission in layer 2/3 of the rat auditory cortex.
abstract: Noradrenergic terminals from the locus coeruleus release norepinephrine (NE) throughout most brain areas, including the auditory cortex, where they affect neural processing by modulating numerous cellular properties including the inhibitory γ-aminobutyric acid (GABA)ergic transmission. We recently demonstrated that NE affects GABAergic signaling onto cortical pyramidal cells in a complex manner. In this study, we used a combination of patch-clamp recording and immunohistochemical techniques to identify the synaptic site and the location of the adrenergic receptors involved in the modulation of GABAergic signaling in cortical layer 2/3 of the rat. Our results showed that NE increases the frequency of spike-independent miniature inhibitory postsynaptic currents (mIPSCs), as well as the probability of release of unitary inhibitory postsynaptic currents (IPSCs) obtained with patch-clamp pair-recordings. The pharmacology of mIPSCs and the identification of adrenergic receptors in neurons containing the GABAergic marker parvalbumin (PV) suggest that NE increases the presynaptic probability of GABA release by activating α(2) - and β-receptors on PV-positive neurons. On the contrary, bath-applied NE or phenylephrine, decreased the current mediated by pressure application of the GABA(A) -receptor agonist muscimol, as well as the amplitude-but not the frequency-of mIPSCs, indicating that activation of postsynaptic α(1) adrenoceptors reversibly depressed GABAergic currents. We speculate that while a generalized postsynaptic decrease of GABAergic inhibition might decrease the synaptic activation threshold for pyramidal neurons corresponding to an alert state, NE might promote perception and sensory binding by facilitating lateral inhibition as well as the production of γ-oscillations by a selective enhancement of perisomatic inhibition.
authors: University of Texas at Dallas, School of Behavioral and Brain Sciences, Richardson, Texas 75080, USA.
authors: Humberto
authors: H
authors: Salgado
authors: Francisco
authors: F
authors: Garcia-Oscos
authors: Laura
authors: L
authors: Martinolich
authors: Shawn
authors: S
authors: Hall
authors: Robert
authors: R
authors: Restom
authors: Kuei Y
authors: KY
authors: Tseng
authors: Marco
authors: M
authors: Atzori
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D009638:Norepinephrine