Noradrenergic suppression of synaptic transmission may influence cortical signal-to-noise ratio.

Norepinephrine has been proposed to influence signal-to-noise ratio within cortical structures, but the exact cellular mechanisms underlying this influence have not been described in detail. Here we present data on a cellular effect of norepinephrine that could contribute to the influence on signal-to-noise ratio. In brain slice preparations of the rat piriform (olfactory) cortex, perfusion of norepinephrine causes a dose-dependent suppression of excitatory synaptic potentials in the layer containing synapses among pyramidal cells in the cortex (layer Ib), while having a weaker effect on synaptic potentials in the afferent fiber layer (layer Ia). Effects of norepinephrine were similar in dose-response characteristics and laminar selectivity to the effects of the cholinergic agonist carbachol, and combined perfusion of both agonists caused effects similar to an equivalent concentration of a single agonist. In a computational model of the piriform cortex, we have analyzed the effect of noradrenergic suppression of synaptic transmission on signal-to-noise ratio. The selective suppression of excitatory intrinsic connectivity decreases the background activity of modeled neurons relative to the activity of neurons receiving direct afferent input. This can be interpreted as an increase in signal-to-noise ratio, but the term noise does not accurately characterize activity dependent on the intrinsic spread of excitation, which would more accurately be described as interpretation or retrieval. Increases in levels of norepinephrine mediated by locus coeruleus activity appear to enhance the influence of extrinsic input on cortical representations, allowing a pulse of norepinephrine in an arousing context to mediate formation of memories with a strong influence of environmental variables.

[1]  J. Cowan,et al.  Excitatory and inhibitory interactions in localized populations of model neurons. , 1972, Biophysical journal.

[2]  F. Bloom,et al.  The action of norepinephrine in the rat hippocampus. II. Activation of the input pathway. , 1974, Brain research.

[3]  F. Bloom,et al.  The action of norepinephrine in the rat hippocampus. III. Hippocampal cellular responses to locus coeruleus stimulation in the awake rat , 1976, Brain Research.

[4]  F. Bloom,et al.  The action of norepinephrine in the rat hippocampus. IV. The effects of locus coeruleus stimulation on evoked hippocampal unit activity , 1976, Brain Research.

[5]  U. Meyer,et al.  Centrifugal cholinergic connections in the olfactory system of rats , 1977, Neuroscience.

[6]  S. Mewaldt,et al.  The effects and interactions of scopolamine, physostigmine and methamphetamine on human memory , 1979, Pharmacology Biochemistry and Behavior.

[7]  D J Woodward,et al.  Modulatory actions of norepinephrine in the central nervous system. , 1979, Federation proceedings.

[8]  D. Woodward,et al.  Interaction of norepinephrine with cerebrocortical activity evoked by stimulation of somatosensory afferent pathways in the rat , 1980, Experimental Neurology.

[9]  T. Dunwiddie,et al.  Noradrenergic responses in rat hippocampus: Evidence for mediation by α and β receptors in the in vitro slice , 1981, Brain Research.

[10]  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.

[11]  M. Segal.  The action of norepinephrine in the rat hippocampus: Intracellular studies in the slice preparation , 1981, Brain Research.

[12]  F. Bloom,et al.  Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  F E Bloom,et al.  Noradrenergic and serotonergic fibers innervate complementary layers in monkey primary visual cortex: an immunohistochemical study. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Nicoll,et al.  Noradrenergic modulation of dendrodendritic inhibition in the olfactory bulb , 1982, Nature.

[15]  S. Sara,et al.  Memory retrieval enhanced by amphetamine after a long retention interval. , 1982, Behavioral and neural biology.

[16]  T. Dunwiddie,et al.  Anticonvulsant and Proconvulsant Actions of Alpha‐ and Beta‐Noradrenergic Agonists onEpileptiform Activity in Rat Hippocampus In Vitro , 1983, Epilepsia.

[17]  A. Sillito,et al.  Cholinergic modulation of the functional organization of the cat visual cortex , 1983, Brain Research.

[18]  L. Hartley,et al.  The Effect of Beta Adrenergic Blocking Drugs on Speakers' Performance and Memory , 1983, British Journal of Psychiatry.

[19]  Role of norepinephrine in seizurelike activity of hippocampal pyramidal cells maintained in vitro: alteration by 6-hydroxydopamine lesions of norepinephrine-containing systems. , 1983, Canadian journal of physiology and pharmacology.

[20]  F. Bloom,et al.  Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. , 1983, Physiological reviews.

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

[22]  S. Sara,et al.  The locus coeruleus and cognitive function: Attempts to relate noradrenergic enhancement of signal/noise in the brain to behavior , 1985 .

[23]  L. Haberly.  Neuronal circuitry in olfactory cortex: anatomy and functional implications , 1985 .

[24]  Michael Frotscher,et al.  Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: A combined light and electron microscopic study , 1985, The Journal of comparative neurology.

[25]  Gary Aston-Jones,et al.  Behavioral functions of locus coeruleus derived from cellular attributes , 1985 .

[26]  G. Collins,et al.  Excitatory and inhibitory effects of dopamine on synaptic transmission in the rat olfactory cortex slice , 1985, Brain Research.

[27]  R. Nicoll,et al.  Actions of noradrenaline recorded intracellularly in rat hippocampal CA1 pyramidal neurones, in vitro. , 1986, The Journal of physiology.

[28]  W. Singer,et al.  Modulation of visual cortical plasticity by acetylcholine and noradrenaline , 1986, Nature.

[29]  R. Wong,et al.  Cellular and synaptic properties of amygdala-kindled pyriform cortex in vitro. , 1986, Journal of neurophysiology.

[30]  F. Schottler,et al.  Role of dorsomedial thalamic nucleus and piriform cortex in processing olfactory information , 1987, Behavioural Brain Research.

[31]  Roger A. Nicoll,et al.  Norepinephrine decreases synaptic inhibition in the rat hippocampus , 1988, Brain Research.

[32]  T. Dunwiddie,et al.  Noradrenergic depression of synaptic responses in hippocampus of rat: Evidence for mediation by alpha1-receptors , 1988, Neuropharmacology.

[33]  D. Johnston,et al.  Noradrenergic enhancement of long-term potentiation at mossy fiber synapses in the hippocampus. , 1988, Journal of neurophysiology.

[34]  L. Haberly,et al.  Characterization of synaptically mediated fast and slow inhibitory processes in piriform cortex in an in vitro slice preparation. , 1988, Journal of neurophysiology.

[35]  C. Montigny,et al.  Electrophysiological characterization of adrenoceptors in the rat dorsal hippocampus. I. Receptors mediating the effect of microiontophoretically applied norepinephrine , 1988, Brain Research.

[36]  J. Bower,et al.  Olfactory cortex: model circuit for study of associative memory? , 1989, Trends in Neurosciences.

[37]  S. Sara,et al.  Idazoxan, an α-2 antagonist, facilitates memory retrieval in the rat , 1989 .

[38]  L. Haberly,et al.  Deep neurons in piriform cortex. II. Membrane properties that underlie unusual synaptic responses. , 1989, Journal of neurophysiology.

[39]  J. D. McGaugh,et al.  Concurrent muscarinic and β-adrenergic blockade in rats impairs place-learning in a water maze and retention of inhibitory avoidance , 1990, Brain Research.

[40]  P. Brennan,et al.  Olfactory recognition: a simple memory system. , 1990, Science.

[41]  R. Gaykema,et al.  Cortical projection patterns of the medial septum‐diagonal band complex , 1990, The Journal of comparative neurology.

[42]  J D Cohen,et al.  A network model of catecholamine effects: gain, signal-to-noise ratio, and behavior. , 1990, Science.

[43]  N. Weinberger,et al.  Cholinergic modulation of responses to single tones produces tone‐specific receptive field alterations in cat auditory cortex , 1990, Synapse.

[44]  J. Sarvey,et al.  Muscarinic receptor activation facilitates the induction of long-term potentiation (LTP) in the rat dentate gyrus , 1990, Neuroscience Letters.

[45]  Hans-Ulrich Dodt,et al.  Actions of noradrenaline on neocortical neurons in vitro , 1991, Brain Research.

[46]  D. Wilson,et al.  Olfactory associative conditioning in infant rats with brain stimulation as reward: II. Norepinephrine mediates a specific component of the bulb response to reward. , 1991, Behavioral Neuroscience.

[47]  N. Weinberger,et al.  Acetylcholine Modulation of Cellular Excitability Via Muscarinic Receptors: Functional Plasticity in Auditory Cortex , 1991 .

[48]  D. Wilson,et al.  Neural correlates of conditioned odor avoidance in infant rats. , 1991, Behavioral neuroscience.

[49]  D. Madison,et al.  Synaptic localization of adrenergic disinhibition in the rat hippocampus , 1991, Neuron.

[50]  M. Hasselmo,et al.  Selective suppression of afferent but not intrinsic fiber synaptic transmission by 2-amino-4-phosphonobutyric acid (AP4) in piriform cortex , 1991, Brain Research.

[51]  J. Cohen,et al.  Context, cortex, and dopamine: a connectionist approach to behavior and biology in schizophrenia. , 1992, Psychological review.

[52]  W. Singer,et al.  Agonists of cholinergic and noradrenergic receptors facilitate synergistically the induction of long-term potentiation in slices of rat visual cortex , 1992, Brain Research.

[53]  M. Hasselmo,et al.  Cholinergic suppression specific to intrinsic not afferent fiber synapses in rat piriform (olfactory) cortex. , 1992, Journal of neurophysiology.

[54]  G M Shepherd,et al.  Noradrenergic inhibition of synaptic transmission between mitral and granule cells in mammalian olfactory bulb cultures , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  J. Bower,et al.  Differential Effects of Norepinephrine on Synaptic Transmission in Layers 1A and 1B of Rat Olfactory Cortex , 1993 .

[56]  M. Hasselmo,et al.  Acetylcholine and memory , 1993, Trends in Neurosciences.

[57]  J. Lisman,et al.  Heightened synaptic plasticity of hippocampal CA1 neurons during a Cholinergically induced rhythmic state , 1993, Nature.

[58]  G. Aghajanian,et al.  Pyramidal cells in piriform cortex receive a convergence of inputs from monoamine activated GABAergic interneurons , 1993, Brain Research.

[59]  D. Wilson,et al.  Role of the amygdala complex in early olfactory associative learning. , 1993, Behavioral neuroscience.

[60]  B. Gähwiler,et al.  Presynaptic inhibition of excitatory synaptic transmission mediated by alpha adrenergic receptors in area CA3 of the rat hippocampus in vitro , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[61]  M. Hasselmo,et al.  Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[62]  Bao-Ming Li,et al.  Delayed-response deficit induced by local injection of the alpha 2-adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys. , 1994, Behavioral and neural biology.

[63]  M. Hasselmo,et al.  Selective suppression of intrinsic but not afferent fiber synaptic transmission by baclofen in the piriform (olfactory) cortex , 1994, Brain Research.

[64]  R. Sullivan,et al.  Norepinephrine and posttraining memory consolidation in neonatal rats , 1994 .

[65]  M. Hasselmo,et al.  Modulation of the input/output function of rat piriform cortex pyramidal cells. , 1994, Journal of neurophysiology.

[66]  R. Sullivan,et al.  The locus coeruleus, norepinephrine, and memory in newborns , 1994, Brain Research Bulletin.

[67]  M. Hasselmo.  Neuromodulation and cortical function: modeling the physiological basis of behavior , 1995, Behavioural Brain Research.

[68]  M. Hasselmo,et al.  Dynamics of learning and recall at excitatory recurrent synapses and cholinergic modulation in rat hippocampal region CA3 , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[69]  M. Ohno,et al.  Concurrent blockade of β-adrenergic and muscarinic receptors disrupts working memory but not reference memory in rats , 1995, Physiology & Behavior.

[70]  M. Hasselmo,et al.  Cholinergic modulation of activity-dependent synaptic plasticity in the piriform cortex and associative memory function in a network biophysical simulation , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[71]  M. Hasselmo,et al.  Suppression of synaptic transmission may allow combination of associative feedback and self-organizing feedforward connections in the neocortex , 1996, Behavioural Brain Research.

[72]  Cholinergic modulation of inhibitory synaptic transmission in the piriform cortex , 1997 .

[73]  M. Hasselmo,et al.  Modulation of inhibition in a model of olfactory bulb reduces overlap in the neural representation of olfactory stimuli , 1997, Behavioural Brain Research.