Cholinergic control of cortical network interactions enables feedback‐mediated attentional modulation

Attention increases our ability to detect behaviorally relevant stimuli. At the neuronal level this is supported by increased firing rates of neurons representing the attended object. In primary visual cortex an attention‐mediated activity increase depends on the presence of the neuromodulator acetylcholine. Using a spiking network model of visual cortex we have investigated how acetylcholine interacts with biased feedback to enable attentional processing. Although acetylcholine affects cortical processing in a multitude of manners, we restricted our analysis to four of its main established actions. These were (i) a reduction in firing rate adaptation by reduction in M‐currents (muscarinic), (ii) an increase in thalamocortical synaptic efficacy by nicotinic presynaptic receptors, (iii) a reduction in lateral interactions by muscarinic presynaptic receptors, and (iv) an increase in inhibitory drive by muscarinic receptors located on inhibitory interneurons. We found that acetylcholine contributes to feedback‐mediated attentional modulation, mostly by reducing intracortical interactions and also to some extent by increasing the inhibitory drive. These findings help explain why acetylcholine is necessary for top–down‐driven attentional modulation, and suggest a close interdependence of cholinergic and feedback drive in mediating cognitive function.

[1]  Jude F. Mitchell,et al.  Differential Attention-Dependent Response Modulation across Cell Classes in Macaque Visual Area V4 , 2007, Neuron.

[2]  X. Wang,et al.  Synaptic Basis of Cortical Persistent Activity: the Importance of NMDA Receptors to Working Memory , 1999, The Journal of Neuroscience.

[3]  M. Silver,et al.  Cholinergic Enhancement Augments Magnitude and Specificity of Visual Perceptual Learning in Healthy Humans , 2010, Current Biology.

[4]  Harvey A Swadlow,et al.  Task difficulty modulates the activity of specific neuronal populations in primary visual cortex , 2008, Nature Neuroscience.

[5]  Louise S. Delicato,et al.  Acetylcholine contributes through muscarinic receptors to attentional modulation in V1 , 2008, Nature.

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

[7]  M. Hawken,et al.  Gain Modulation by Nicotine in Macaque V1 , 2007, Neuron.

[8]  D. Whitteridge,et al.  Innervation of cat visual areas 17 and 18 by physiologically identified X‐ and Y‐ type thalamic afferents. I. Arborization patterns and quantitative distribution of postsynaptic elements , 1985, The Journal of comparative neurology.

[9]  Maurizio Mattia,et al.  Finite-size dynamics of inhibitory and excitatory interacting spiking neurons. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[10]  B. Connors,et al.  Differential Regulation of Neocortical Synapses by Neuromodulators and Activity , 1997, Neuron.

[11]  R. Desimone,et al.  Selective attention gates visual processing in the extrastriate cortex. , 1985, Science.

[12]  A. Thiele,et al.  A novel electrode–pipette design for simultaneous recording of extracellular spikes and iontophoretic drug application in awake behaving monkeys , 2006, Journal of Neuroscience Methods.

[13]  S. Epstein,et al.  Background gamma rhythmicity and attention in cortical local circuits: a computational study. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  S. Cruikshank,et al.  Differential modulation of auditory thalamocortical and intracortical synaptic transmission by cholinergic agonist , 2000, Brain Research.

[15]  A. Burkhalter,et al.  A Polysynaptic Feedback Circuit in Rat Visual Cortex , 1997, The Journal of Neuroscience.

[16]  E. Rolls,et al.  Neurodynamics of biased competition and cooperation for attention: a model with spiking neurons. , 2005, Journal of neurophysiology.

[17]  D. A. Brown,et al.  Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone , 1980, Nature.

[18]  D. McCormick,et al.  Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. , 1985, Journal of neurophysiology.

[19]  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.

[20]  Pietro Pietrini,et al.  Selective Effects of Cholinergic Modulation on Task Performance during Selective Attention , 2008, Neuropsychopharmacology.

[21]  Paul Antoine Salin,et al.  Spontaneous GABAA receptor-mediated inhibitory currents in adult rat somatosensory cortex. , 1996, Journal of neurophysiology.

[22]  P. H. Schiller,et al.  State dependent activity in monkey visual cortex , 2004, Experimental Brain Research.

[23]  R. Desimone,et al.  Neural mechanisms of spatial selective attention in areas V1, V2, and V4 of macaque visual cortex. , 1997, Journal of neurophysiology.

[24]  D. Prince,et al.  GABAA receptor‐mediated currents in interneurons and pyramidal cells of rat visual cortex , 1998, The Journal of physiology.

[25]  B. Ermentrout Neural networks as spatio-temporal pattern-forming systems , 1998 .

[26]  Louise S. Delicato,et al.  Attention Reduces Stimulus-Driven Gamma Frequency Oscillations and Spike Field Coherence in V1 , 2010, Neuron.

[27]  L. Chelazzi Serial attention mechanisms in visual search: A critical look at the evidence , 1999, Psychological research.

[28]  D. Whitteridge,et al.  Arborisation pattern and postsynaptic targets of physiologically identified thalamocortical afferents in striate cortex of the macaque monkey , 1989, The Journal of comparative neurology.

[29]  A. Thiele,et al.  Attention – oscillations and neuropharmacology , 2009, The European journal of neuroscience.

[30]  N. Weinberger,et al.  Specific auditory memory induced by nucleus basalis stimulation depends on intrinsic acetylcholine , 2008, Neurobiology of Learning and Memory.

[31]  J. Fellous,et al.  A role for NMDA-receptor channels in working memory , 1998, Nature Neuroscience.

[32]  L. Descarries,et al.  Cholinergic innervation in adult rat cerebral cortex: A quantitative immunocytochemical description , 2000, The Journal of comparative neurology.

[33]  C. Aoki,et al.  Differential expression of muscarinic acetylcholine receptors across excitatory and inhibitory cells in visual cortical areas V1 and V2 of the macaque monkey , 2006, The Journal of comparative neurology.

[34]  G. Stuart,et al.  Cholinergic Inhibition of Neocortical Pyramidal Neurons , 2005, The Journal of Neuroscience.

[35]  M. Feinberg,et al.  Specificity in inhibitory systems associated with prefrontal pathways to temporal cortex in primates. , 2007, Cerebral cortex.

[36]  John Duncan,et al.  A neural basis for visual search in inferior temporal cortex , 1993, Nature.

[37]  D. J. Felleman,et al.  Distributed hierarchical processing in the primate cerebral cortex. , 1991, Cerebral cortex.

[38]  A. Destexhe Kinetic Models of Synaptic Transmission , 1997 .

[39]  Carrie J. McAdams,et al.  Effects of Attention on Orientation-Tuning Functions of Single Neurons in Macaque Cortical Area V4 , 1999, The Journal of Neuroscience.

[40]  Evan S. Schaffer,et al.  Inhibitory Stabilization of the Cortical Network Underlies Visual Surround Suppression , 2009, Neuron.

[41]  A. BROWN,et al.  Beta-Polymorphs of Uranium and Thorium Disilicides , 1959, Nature.

[42]  A. Thiele,et al.  Acetylcholine dynamically controls spatial integration in marmoset primary visual cortex. , 2005, Journal of neurophysiology.

[43]  Andreas V. M. Herz,et al.  A Universal Model for Spike-Frequency Adaptation , 2003, Neural Computation.

[44]  R. Desimone,et al.  High-Frequency, Long-Range Coupling Between Prefrontal and Visual Cortex During Attention , 2009, Science.

[45]  J. Berger-Sweeney,et al.  Cholinergic regulation of cortical development and plasticity. New twists to an old story. , 1998, Perspectives on developmental neurobiology.

[46]  A. Thiele,et al.  Cholinergic modulation of response properties and orientation tuning of neurons in primary visual cortex of anaesthetized Marmoset monkeys , 2006, The European journal of neuroscience.

[47]  S. Epstein,et al.  Gamma oscillations mediate stimulus competition and attentional selection in a cortical network model , 2008, Proceedings of the National Academy of Sciences.

[48]  E. Miller,et al.  Suppression of visual responses of neurons in inferior temporal cortex of the awake macaque by addition of a second stimulus , 1993, Brain Research.

[49]  H. Spitzer,et al.  Increased attention enhances both behavioral and neuronal performance. , 1988, Science.

[50]  R. Nicoll,et al.  Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices , 1990, Neuron.

[51]  B. C. Motter Focal attention produces spatially selective processing in visual cortical areas V1, V2, and V4 in the presence of competing stimuli. , 1993, Journal of neurophysiology.

[52]  C. Aoki,et al.  Muscarinic acetylcholine receptors in macaque V1 are most frequently expressed by parvalbumin‐immunoreactive neurons , 2008, The Journal of comparative neurology.

[53]  M. Hasselmo,et al.  Noradrenergic suppression of synaptic transmission may influence cortical signal-to-noise ratio. , 1997, Journal of neurophysiology.

[54]  D. Prince,et al.  GABA A receptor-mediated currents in interneurons and pyramidal cells of rat visual cortex , 1998 .

[55]  Pieter R. Roelfsema,et al.  Object-based attention in the primary visual cortex of the macaque monkey , 1998, Nature.

[56]  A.,et al.  Spontaneous GABA * Receptor-Mediated Inhibitory Currents in Adult Rat Somatosensory Cortex , 2002 .

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

[58]  A. Thiele,et al.  Attention alters spatial integration in macaque V1 in an eccentricity-dependent manner , 2007, Nature Neuroscience.

[59]  Lisa M. Giocomo,et al.  Cholinergic modulation of cortical function , 2007, Journal of Molecular Neuroscience.

[60]  Katherine M. Armstrong,et al.  Selective gating of visual signals by microstimulation of frontal cortex , 2003, Nature.

[61]  P. Tiesinga,et al.  Role of interneuron diversity in the cortical microcircuit for attention. , 2008, Journal of neurophysiology.

[62]  Kevan A C Martin,et al.  Synaptic connection from cortical area V4 to V2 in macaque monkey , 2006, The Journal of comparative neurology.

[63]  R. Desimone,et al.  The Role of Neural Mechanisms of Attention in Solving the Binding Problem , 1999, Neuron.

[64]  D. McCormick,et al.  Mechanisms of action of acetylcholine in the guinea‐pig cerebral cortex in vitro. , 1986, The Journal of physiology.

[65]  R. Desimone,et al.  Modulation of Oscillatory Neuronal Synchronization by Selective Visual Attention , 2001, Science.

[66]  Y. Frégnac,et al.  Involvement of nicotinic and muscarinic receptors in the endogenous cholinergic modulation of the balance between excitation and inhibition in the young rat visual cortex. , 2009, Cerebral cortex.

[67]  L. Descarries,et al.  Acetylcholine innervation of sensory and motor neocortical areas in adult cat: a choline acetyltransferase immunohistochemical study , 1996, Journal of Chemical Neuroanatomy.

[68]  C. Sánchez-Camacho,et al.  Basal forebrain cholinergic system of the anuran amphibian Rana perezi: Evidence for a shared organization pattern with amniotes , 2006, The Journal of comparative neurology.

[69]  Aaron R. Seitz,et al.  A unified model for perceptual learning , 2005, Trends in Cognitive Sciences.

[70]  P. Goldman-Rakic,et al.  Preface: Cerebral Cortex Has Come of Age , 1991 .

[71]  Fumitaka Kimura,et al.  Cholinergic modulation of cortical function: A hypothetical role in shifting the dynamics in cortical network , 2000, Neuroscience Research.

[72]  C. Stevens,et al.  Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[73]  Paul H. E. Tiesinga,et al.  Attentional modulation of firing rate and synchrony in a model cortical network , 2005, Journal of Computational Neuroscience.

[74]  N. Spruston,et al.  Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons. , 1995, The Journal of physiology.

[75]  D. Amit,et al.  Model of global spontaneous activity and local structured activity during delay periods in the cerebral cortex. , 1997, Cerebral cortex.