Enhancement of Signal-to-Noise Ratio and Phase Locking for Small Inputs by a Low-Threshold Outward Current in Auditory Neurons

Neurons possess multiple voltage-dependent conductances specific for their function. To investigate how low-threshold outward currents improve the detection of small signals in a noisy background, we recorded from gerbil medial superior olivary (MSO) neurons in vitro. MSO neurons responded phasically, with a single spike to a step current injection. When bathed in dendrotoxin (DTX), most cells switched to tonic firing, suggesting that low-threshold potassium currents (IKLT) participated in shaping these phasic responses. Neurons were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the “noise”), together with a larger but still subthreshold postsynaptic conductance, EPSG (the “signal”). DTX reduced the signal-to-noise ratio (SNR), defined as the ratio of probability to fire in response to the EPSG and the probability to fire spontaneously in response to noise. The reduction was mainly attributable to the increase of spontaneous firing in DTX. The spike-triggered reverse correlation indicated that, for spike generation, the neuron with IKLTrequired faster inward current transients. This narrow temporal integration window contributed to superior phase locking of firing to periodic stimuli before application of DTX. A computer model including Hodgkin-Huxley type conductances for spike generation and forIKLT (Rathouz and Trussell, 1998) showed similar response statistics. The dynamic low-threshold outward current increased SNR and the temporal precision of integration of weak subthreshold signals in auditory neurons by suppressing false positives.

[1]  L A JEFFRESS,et al.  A place theory of sound localization. , 1948, Journal of comparative and physiological psychology.

[2]  J. Goldberg,et al.  Response of binaural neurons of dog superior olivary complex to dichotic tonal stimuli: some physiological mechanisms of sound localization. , 1969, Journal of neurophysiology.

[3]  H. L. Bryant,et al.  Spike initiation by transmembrane current: a white‐noise analysis. , 1976, The Journal of physiology.

[4]  M. Liberman,et al.  Auditory-nerve response from cats raised in a low-noise chamber. , 1978, The Journal of the Acoustical Society of America.

[5]  M. Liberman Single-neuron labeling in the cat auditory nerve. , 1982, Science.

[6]  D. Oertel Synaptic responses and electrical properties of cells in brain slices of the mouse anteroventral cochlear nucleus , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  G K Martin,et al.  Effects of reaction time performance on single-unit activity in the central auditory pathway of the rhesus macaque , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  William H. Press,et al.  Numerical recipes in C. The art of scientific computing , 1987 .

[9]  E. Rubel,et al.  Embryogenesis of arborization pattern and topography of individual axons in N. Laminaris of the chicken brain stem , 1986, The Journal of comparative neurology.

[10]  F. A. Seiler,et al.  Numerical Recipes in C: The Art of Scientific Computing , 1989 .

[11]  M. Konishi,et al.  A circuit for detection of interaural time differences in the brain stem of the barn owl , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  P. Manis,et al.  Outward currents in isolated ventral cochlear nucleus neurons , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  T. Sejnowski,et al.  Simulations of cortical pyramidal neurons synchronized by inhibitory interneurons. , 1991, Journal of neurophysiology.

[14]  M. Liberman Central projections of auditory‐nerve fibers of differing spontaneous rate. I. Anteroventral cochlear nucleus , 1991, The Journal of comparative neurology.

[15]  I. Raman,et al.  The kinetics of the response to glutamate and kainate in neurons of the avian cochlear nucleus , 1992, Neuron.

[16]  Eve Marder,et al.  The dynamic clamp: artificial conductances in biological neurons , 1993, Trends in Neurosciences.

[17]  M. Liberman Central projections of auditory nerve fibers of differing spontaneous rate, II: Posteroventral and dorsal cochlear nuclei , 1993, The Journal of comparative neurology.

[18]  William R. Softky,et al.  The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  A. Reyes,et al.  Membrane properties underlying the firing of neurons in the avian cochlear nucleus , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  William R. Softky,et al.  Sub-millisecond coincidence detection in active dendritic trees , 1994, Neuroscience.

[21]  P X Joris,et al.  Enhancement of neural synchronization in the anteroventral cochlear nucleus. II. Responses in the tuning curve tail. , 1994, Journal of neurophysiology.

[22]  T. Fujita,et al.  Developmental change in fast Na channel properties in embryonic chick ventricular heart cells. , 1995, Canadian journal of physiology and pharmacology.

[23]  Kurt Wiesenfeld,et al.  Stochastic resonance and the benefits of noise: from ice ages to crayfish and SQUIDs , 1995, Nature.

[24]  Sergey M. Bezrukov,et al.  Noise-induced enhancement of signal transduction across voltage-dependent ion channels , 1995, Nature.

[25]  O. Prospero-Garcia,et al.  Reliability of Spike Timing in Neocortical Neurons , 1995 .

[26]  P. H. Smith,et al.  Structural and functional differences distinguish principal from nonprincipal cells in the guinea pig MSO slice. , 1995, Journal of neurophysiology.

[27]  I. Forsythe,et al.  Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  A. Reyes,et al.  In vitro analysis of optimal stimuli for phase-locking and time-delayed modulation of firing in avian nucleus laminaris neurons , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  B. Robertson,et al.  Novel effects of dendrotoxin homologues on subtypes of mammalian Kv1 potassium channels expressed in Xenopus oocytes , 1996, FEBS letters.

[30]  J. Rothman,et al.  Enhancement of neural synchronization in computational models of ventral cochlear nucleus bushy cells , 1996 .

[31]  L. Trussell,et al.  Characterization of outward currents in neurons of the avian nucleus magnocellularis. , 1998, Journal of neurophysiology.

[32]  S. Schmid,et al.  Alterations in channel density and kinetic properties of the sodium current in retinal ganglion cells of the rat during in vivo differentiation , 1998, Neuroscience.

[33]  J. D. Hunter,et al.  Resonance effect for neural spike time reliability. , 1998, Journal of neurophysiology.

[34]  B. Robertson,et al.  Identification of residues in dendrotoxin K responsible for its discrimination between neuronal K+ channels containing Kv1.1 and 1.2 alpha subunits. , 1999, European journal of biochemistry.

[35]  Christof Koch,et al.  Detecting and Estimating Signals in Noisy Cable Structures, II: Information Theoretical Analysis , 1999, Neural Computation.

[36]  L. Trussell,et al.  Synaptic mechanisms for coding timing in auditory neurons. , 1999, Annual review of physiology.

[37]  L. Trussell,et al.  Time Course and Permeation of Synaptic AMPA Receptors in Cochlear Nuclear Neurons Correlate with Input , 1999, The Journal of Neuroscience.

[38]  D. Jaeger,et al.  The Control of Rate and Timing of Spikes in the Deep Cerebellar Nuclei by Inhibition , 2000, The Journal of Neuroscience.

[39]  P. Joris,et al.  Detection of synchrony in the activity of auditory nerve fibers by octopus cells of the mammalian cochlear nucleus. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[40]  J. McGee,et al.  Contributions of ion conductances to the onset responses of octopus cells in the ventral cochlear nucleus: simulation results. , 2000, Journal of neurophysiology.

[41]  D. Oertel,et al.  Potassium currents in octopus cells of the mammalian cochlear nucleus. , 2001, Journal of neurophysiology.

[42]  L. Carney,et al.  A phenomenological model for the responses of auditory-nerve fibers: I. Nonlinear tuning with compression and suppression. , 2001, The Journal of the Acoustical Society of America.

[43]  M. Ferragamo,et al.  Octopus cells of the mammalian ventral cochlear nucleus sense the rate of depolarization. , 2002, Journal of neurophysiology.

[44]  William H. Press,et al.  Numerical recipes in C , 2002 .

[45]  John Rinzel,et al.  Influence of subthreshold nonlinearities on signal-to-noise ratio and timing precision for small signals in neurons: minimal model analysis. , 2003, Network.

[46]  W. F. Hopkins,et al.  Properties of voltage-gated K+ currents expressed inXenopus oocytes by mKv1.1, mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin-binding site in mKv1.1 , 1994, Pflügers Archiv.