Individual and additive effects of neuromodulators on the slow components of afterhyperpolarization currents in layer V pyramidal cells of the rat medial prefrontal cortex

The effects of 5-hydroxytryptamine (5-HT), noradrenaline (NA), dopamine (DA) and the muscarinic receptor agonist carbachol (CCh) on the voltage step-induced outward currents underlying afterhyperpolarization (AHP), consisting of a medium (I(mAHP)) and slow (I(sAHP)) component, were investigated in layer V pyramidal cells of the rat medial prefrontal cortex (mPFC). Whole-cell voltage clamp recordings were performed in vitro to quantitatively measure I(mAHP) and I(sAHP) and to examine their functional link to spike-frequency adaptation in the presence of agonists. CCh, 5-HT and NA all reduced the I(sAHP) and the spike adaptation, and, in some cells, replaced the I(sAHP) by the slow inward currents (I(sADP)) underlying the slow afterdepolarization (sADP). DA, however, failed to increase the frequency despite its comparable inhibition of the I(sAHP) over a range of concentrations. In order to test the neuromodulator agonists to see if they have additive actions on the I(sAHP), the effects of co-application of two agonists that increased spike-frequency, 5-HT+NA, 5-HT+CCh and CCh+NA, all at the concentration 30 microM were examined. Specific combinations that included CCh showed additive effects on the slow afterpolarization currents, possibly via both inhibition of I(sAHP) and generation of I(sADP). These findings suggest that neuromodulators have differential effects on the link between the I(sAHP) modulation and spike-frequency adaptation, and that they could exert additive effects on the slow aftercurrents following a strong excitation and, therefore, regulate the repetitive firing properties of the output cells of the rat mPFC.

[1]  R. Nicoll,et al.  Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro. , 1984, The Journal of physiology.

[2]  CR Yang,et al.  Dopamine D1 receptor actions in layers V-VI rat prefrontal cortex neurons in vitro: modulation of dendritic-somatic signal integration , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  Y. Watanabe,et al.  Cellular and subcellular localization of alpha-1 adrenoceptors in the rat visual cortex , 2006, Neuroscience.

[4]  Z. Rossetti,et al.  Noradrenaline and Dopamine Elevations in the Rat Prefrontal Cortex in Spatial Working Memory , 2005, The Journal of Neuroscience.

[5]  G. Hirst,et al.  The slow calcium‐dependent potassium current in a myenteric neurone of the guinea‐pig ileum. , 1985, The Journal of physiology.

[6]  G. Aston-Jones,et al.  Enhanced norepinephrine release in prefrontal cortex with burst stimulation of the locus coeruleus , 1996, Brain Research.

[7]  Y. Kawaguchi,et al.  Selective cholinergic modulation of cortical GABAergic cell subtypes. , 1997, Journal of neurophysiology.

[8]  M. Mesulam,et al.  Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6) , 1983, Neuroscience.

[9]  D. Jenkinson,et al.  Toxins in the characterization of potassium channels , 1989, Trends in Neurosciences.

[10]  P. Schwindt,et al.  Slow conductances in neurons from cat sensorimotor cortex in vitro and their role in slow excitability changes. , 1988, Journal of neurophysiology.

[11]  R. Nicoll,et al.  The coupling of neurotransmitter receptors to ion channels in the brain. , 1988, Science.

[12]  B. Lancaster,et al.  SK channels and the varieties of slow after‐hyperpolarizations in neurons , 2003, The European journal of neuroscience.

[13]  P. Pedarzani,et al.  An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Adams,et al.  Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons. , 1986, Journal of neurophysiology.

[15]  P. Goldman-Rakic,et al.  D1 dopamine receptors in prefrontal cortex: involvement in working memory , 1991, Science.

[16]  R. Nicoll,et al.  Cyclic adenosine 3',5'‐monophosphate mediates beta‐receptor actions of noradrenaline in rat hippocampal pyramidal cells. , 1986, The Journal of physiology.

[17]  D. Jaffe,et al.  Multiple effects of dopamine on layer V pyramidal cell excitability in rat prefrontal cortex. , 2001, Journal of neurophysiology.

[18]  G. Nomikos,et al.  Exposure to predator odor stress increases efflux of frontal cortex acetylcholine and monoamines in mice: Comparisons with immobilization stress and reversal by chlordiazepoxide , 2006, Brain Research.

[19]  S. Maier,et al.  Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex , 2003, Neuropsychopharmacology.

[20]  R. Nicoll,et al.  Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system. , 1990, Physiological reviews.

[21]  M. Molliver,et al.  Organization of raphe-cortical projections in rat: A quantitative retrograde study , 1984, Brain Research Bulletin.

[22]  R. Andrade,et al.  5-Hydroxytryptamine2 and 5-hydroxytryptamine1A receptors mediate opposing responses on membrane excitability in rat association cortex , 1991, Neuroscience.

[23]  R. Nicoll,et al.  Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus , 1982, Nature.

[24]  Johan F. Storm,et al.  Pka mediates the effects of monoamine transmitters on the K+ current underlying the slow spike frequency adaptation in hippocampal neurons , 1993, Neuron.

[25]  Barbara E. Jones,et al.  Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study , 1977, Brain Research.

[26]  T. Robbins,et al.  Distinct Changes in Cortical Acetylcholine and Noradrenaline Efflux during Contingent and Noncontingent Performance of a Visual Attentional Task , 2001, The Journal of Neuroscience.

[27]  M. Sarter,et al.  Sustained Visual Attention Performance-Associated Prefrontal Neuronal Activity: Evidence for Cholinergic Modulation , 2000, The Journal of Neuroscience.

[28]  J. Connor,et al.  Specific involvement of Ca(2+)-calmodulin kinase II in cholinergic modulation of neuronal responsiveness. , 1992, Journal of neurophysiology.

[29]  P. Celada,et al.  Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: involvement of serotonin and GABA. , 2004, Cerebral cortex.

[30]  H. Fibiger,et al.  Conditioned and Unconditioned Stimuli Increase Frontal Cortical and Hippocampal Acetylcholine Release: Effects of Novelty, Habituation, and Fear , 1996, The Journal of Neuroscience.

[31]  W. Chen,et al.  Different mechanisms underlying the repolarization of narrow and wide action potentials in pyramidal cells and interneurons of cat motor cortex , 1996, Neuroscience.

[32]  M. Sarter,et al.  Modulators in concert for cognition: Modulator interactions in the prefrontal cortex , 2007, Progress in Neurobiology.

[33]  Michael E. Hasselmo,et al.  Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection , 2005, Brain Research Reviews.

[34]  F. Bloom,et al.  Nonrepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  H. Saito,et al.  Effects of conditioned fear stress on 5-HT release in the rat prefrontal cortex , 1995, Pharmacology Biochemistry and Behavior.

[36]  A. Arnsten,et al.  Adrenergic pharmacology and cognition: focus on the prefrontal cortex. , 2007, Pharmacology & therapeutics.

[37]  Jeremy K Seamans,et al.  Mechanisms of dopamine activation of fast-spiking interneurons that exert inhibition in rat prefrontal cortex. , 2002, Journal of neurophysiology.

[38]  O. Lindvall,et al.  The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method. , 1974, Acta physiologica Scandinavica. Supplementum.

[39]  J. Lund,et al.  Dopamine and the neural circuitry of primate prefrontal cortex: implications for schizophrenia research. , 1992, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[40]  R. Andrade,et al.  Serotonergic regulation of calcium‐activated potassium currents in rodent prefrontal cortex , 2005, The European journal of neuroscience.

[41]  Yan Dong,et al.  Dopamine D1-Class Receptors Selectively Modulate a Slowly Inactivating Potassium Current in Rat Medial Prefrontal Cortex Pyramidal Neurons , 2003, The Journal of Neuroscience.

[42]  Y. Kawaguchi,et al.  Groupings of nonpyramidal and pyramidal cells with specific physiological and morphological characteristics in rat frontal cortex. , 1993, Journal of neurophysiology.

[43]  Dany Arsenault,et al.  Gain modulation by serotonin in pyramidal neurones of the rat prefrontal cortex , 2005, The Journal of physiology.

[44]  D. Jaffe,et al.  Dopamine Decreases the Excitability of Layer V Pyramidal Cells in the Rat Prefrontal Cortex , 1998, The Journal of Neuroscience.

[45]  Edith Hamel,et al.  5-HT3 Receptors Mediate Serotonergic Fast Synaptic Excitation of Neocortical Vasoactive Intestinal Peptide/Cholecystokinin Interneurons , 2002, The Journal of Neuroscience.

[46]  P. Schwindt,et al.  Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro. , 1988, Journal of neurophysiology.

[47]  R. Nicoll,et al.  Dopamine decreases the calcium-activated afterhyperpolarization in hippocampal CA1 pyramidal cells , 1986, Brain Research.

[48]  P. Sah,et al.  Independent roles of calcium and voltage‐dependent potassium currents in controlling spike frequency adaptation in lateral amygdala pyramidal neurons , 2005, The European journal of neuroscience.

[49]  S. Maier,et al.  Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus , 2005, Nature Neuroscience.

[50]  P. Schwindt,et al.  Norepinephrine selectively reduces slow Ca2+- and Na+-mediated K+ currents in cat neocortical neurons. , 1989, Journal of neurophysiology.

[51]  Pankaj Sah,et al.  Physiological Role of Calcium-Activated Potassium Currents in the Rat Lateral Amygdala , 2002, The Journal of Neuroscience.

[52]  S. Haj-Dahmane,et al.  Ionic mechanism of the slow afterdepolarization induced by muscarinic receptor activation in rat prefrontal cortex. , 1998, Journal of neurophysiology.

[53]  N. Gorelova,et al.  Dopamine D1/D5 receptor activation modulates a persistent sodium current in rat prefrontal cortical neurons in vitro. , 2000, Journal of neurophysiology.

[54]  K. Pribram,et al.  Arousal, activation, and effort in the control of attention. , 1975, Psychological review.

[55]  S. Sesack,et al.  Ultrastructural localization of serotonin2A receptors in the middle layers of the rat prelimbic prefrontal cortex , 2003, Neuroscience.