Convergence and divergence of neurotransmitter action in human cerebral cortex.

Abstract

The postsynaptic actions of acetylcholine, adenosine, yaminobutyric acid, histamine, norepinephrine, and serotonin were analyzed in human cortical pyramidal cells maintained in vitro. The actions of these six putative neurotransmitters converged onto three distinct potassium currents.Application of acetylcholine, histamine, norepinephrine, or serotonin all increased spiking by reducing spike-frequency adaptation, in part by reducing the current that underlies the slow afterhyperpolarization. In addition, application of muscarinic receptor agonists to all neurons or of serotonin to middle-layer cells substantially reduced or blocked the Mcurrent (a K+ current that is voltage and time dependent).Inhibition of neuronal firing was elicited by adenosine, baclofen (a yaminobutyric acid type B receptor agonist), or serotonin and appeared to be due to an increase in the same potassium current by all three agents. These data reveal that individual neuronal currents in the human cerebral cortex are under the control of several putative neurotransmitters and that each neurotransmitter may exhibit more than one postsynaptic action. The specific anatomical connections of these various neurotransmitter systems, as well as their heterogeneous distribution of postsynaptic receptors and responses, allows each to make a specific contribution to the modulation of cortical activity.

Functional Specificity of Gαqand Gα11in the Cholinergic and Glutamatergic Modulation of Potassium Currents and Excitability in Hippocampal Neurons

“…Beside modulating sI AHP , muscarinic and mGluR agonists induce a depolarization of the membrane potential in CA1 neurons. The underlying current has been ascribed to the inhibition of at least two types of K ϩ currents: the voltage-dependent M current (Brown and Adams, 1980;Halliwell and Adams, 1982;McCormick and Williamson, 1989) and a voltage-independent leak current (Madison et al, 1987;Guerineau et al, 1994). More recently, a cation nonselective current has been proposed to be mainly responsible for the depolarization generated by muscarinic and mGluR agonists in cortical and hippocampal neurons (Crepel et al, 1994;Greene et al, 1994;Guerineau et al, 1995;HajDahmane andAndrade, 1997, 1999).…”

Neuronal Activity of Histaminergic Tuberomammillary Neurons During Wake–Sleep States in the Mouse

“…An increase in histaminergic transmission enhances W, whereas its blockade causes somnolence (for review, see Lin, 2000). HA induces a switch in neuronal firing mode from rhythmic burst to single spike activity in thalamic relay neurons (McCormick and Williamson, 1991) and an increase in spiking by reducing spikefrequency adaptation (McCormick and Williamson, 1989). In addition, HA stimulates cholinergic neurons of the brainstem and basal forebrain (Khateb et al, 1995;Lin et al, 1996;Crochet and Sakai, 1999;Koyama and Sakai, 2000) and serotonergic neurons of the DRN (Sakai and Crochet, 2000;Brown et al, 2002), both implicated in waking and attention.…”

Cholinergic Inhibition of Neocortical Pyramidal Neurons

“…Studies using intracellular current-clamp recordings have generally found mAChR activation to be excitatory, producing depolarizing responses in neurons and facilitating action potential generation (Krnjevic et al, 1971;McCormick andPrince, 1985, 1986;Schwindt et al, 1988;Halliwell, 1989;Andrade, 1991;Metherate et al, 1992;Wang and McCormick, 1993;Gloveli et al, 1999;Egorov et al, 2002Egorov et al, , 2003. These direct excitatory effects have been attributed to mAChR-mediated inhibition of potassium conductances (Krnjevic et al, 1971;Schwindt et al, 1988;McCormick and Williamson, 1989;McCormick, 1990;Nishikawa et al, 1994), although more recent data suggest that ACh may also increase activation of a nonselective cation conductance (Andrade, 1991;Andrade, 1996, 1998;Klink and Alonso, 1997;Shalinsky et al, 2002;Egorov et al, 2003).…”