Axonal Speeding: Shaping Synaptic Potentials in Small Neurons by the Axonal Membrane Compartment

The role of the axonal membrane compartment in synaptic integration is usually neglected. We show here that in interneurons of the cerebellar molecular layer, where dendrites are so short that the somatodendritic domain can be considered isopotential, the axonal membrane contributes a significant part of the cell input capacitance. We examine the impact of axonal membrane on synaptic integration by cutting the axon with two-photon illumination. We find that the axonal compartment acts as a sink for signals generated at fast conductance synapses, thus increasing the initial decay rate of corresponding synaptic potentials over the value predicted from the resistance-capacitance (RC) product of the cell membrane; signals generated at slower synapses are much less affected. This mechanism sharpens the spike firing precision of fast glutamatergic inputs without resorting to multisynaptic pathways.

[1]  A. Marty,et al.  Developmental Changes in Parvalbumin Regulate Presynaptic Ca2+ Signaling , 2005, The Journal of Neuroscience.

[2]  Rafael Yuste,et al.  Multiphoton stimulation of neurons. , 2002, Journal of neurobiology.

[3]  Henrik Jörntell,et al.  Properties of Somatosensory Synaptic Integration in Cerebellar Granule Cells In Vivo , 2006, The Journal of Neuroscience.

[4]  C. Koch,et al.  A brief history of time (constants). , 1996, Cerebral cortex.

[5]  J M Bower,et al.  Quantitative Golgi study of the rat cerebellar molecular layer interneurons using principal component analysis , 1998, The Journal of comparative neurology.

[6]  T. Sears,et al.  The effects of single afferent impulses on the probability of firing of external intercostal motoneurones in the cat , 1982, The Journal of physiology.

[7]  M Migliore,et al.  Dendritic potassium channels in hippocampal pyramidal neurons , 2000, The Journal of physiology.

[8]  Richard Miles,et al.  EPSP Amplification and the Precision of Spike Timing in Hippocampal Neurons , 2000, Neuron.

[9]  B. Sakmann,et al.  Spine Ca2+ Signaling in Spike-Timing-Dependent Plasticity , 2006, The Journal of Neuroscience.

[10]  H. Gerschenfeld,et al.  Inhibitory synaptic currents in stellate cells of rat cerebellar slices. , 1993, The Journal of physiology.

[11]  D. McCormick,et al.  Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential , 2006, Nature.

[12]  Alain Marty,et al.  Multivesicular Release at Single Functional Synaptic Sites in Cerebellar Stellate and Basket Cells , 1998, The Journal of Neuroscience.

[13]  H. Lecar,et al.  Voltage and Patch Clamping with Microelectrodes , 1985, Springer New York.

[14]  W. Rall.  Time constants and electrotonic length of membrane cylinders and neurons. , 1969, Biophysical journal.

[15]  Henrik Jörntell,et al.  Reciprocal Bidirectional Plasticity of Parallel Fiber Receptive Fields in Cerebellar Purkinje Cells and Their Afferent Interneurons , 2002, Neuron.

[16]  D. Debanne,et al.  Action-potential propagation gated by an axonal IA-like K+ conductance in hippocampus , 1997, Nature.

[17]  N. Spruston,et al.  Action potential initiation and backpropagation in neurons of the mammalian CNS , 1997, Trends in Neurosciences.

[18]  A. Marty,et al.  Coexistence of Excitatory and Inhibitory GABA Synapses in the Cerebellar Interneuron Network , 2003, The Journal of Neuroscience.

[19]  D. Pinkel,et al.  Supporting Online Material Materials and Methods Figs. S1 and S2 Tables S1 and S2 References Combined Analog and Action Potential Coding in Hippocampal Mossy Fibers , 2022 .

[20]  Mehmet Fatih Yanik,et al.  Neurosurgery: Functional regeneration after laser axotomy , 2004, Nature.

[21]  B. Kampa,et al.  Synaptic integration in dendritic trees. , 2005, Journal of neurobiology.

[22]  D. Johnston,et al.  Axonal Action-Potential Initiation and Na+ Channel Densities in the Soma and Axon Initial Segment of Subicular Pyramidal Neurons , 1996, The Journal of Neuroscience.

[23]  C. Pouzat,et al.  Developmental Regulation of Basket/Stellate Cell→Purkinje Cell Synapses in the Cerebellum , 1997, The Journal of Neuroscience.

[24]  Idan Segev,et al.  Space-Clamp Problems When Voltage Clamping Branched Neurons With Intracellular Microelectrodes , 1985 .

[25]  J. Nadal,et al.  Optimal Information Storage and the Distribution of Synaptic Weights Perceptron versus Purkinje Cell , 2004, Neuron.

[26]  Wade G. Regehr,et al.  Quantal events shape cerebellar interneuron firing , 2002, Nature Neuroscience.

[27]  A. Marty,et al.  Presynaptic Effects of NMDA in Cerebellar Purkinje Cells and Interneurons , 1999, The Journal of Neuroscience.

[28]  A. Konnerth,et al.  Synaptic‐ and agonist‐induced excitatory currents of Purkinje cells in rat cerebellar slices. , 1991, The Journal of physiology.

[29]  K. J Suter,et al.  Reliable control of spike rate and spike timing by rapid input transients in cerebellar stellate cells , 2004, Neuroscience.

[30]  B. Clark,et al.  Activity-Dependent Recruitment of Extrasynaptic NMDA Receptor Activation at an AMPA Receptor-Only Synapse , 2002, The Journal of Neuroscience.

[31]  B Sakmann,et al.  Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  I. Llano,et al.  Modulation by K+ channels of action potential‐evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons , 1999, The Journal of physiology.

[33]  Y Yarom,et al.  Electrotonic Coupling Interacts with Intrinsic Properties to Generate Synchronized Activity in Cerebellar Networks of Inhibitory Interneurons , 1999, The Journal of Neuroscience.

[34]  I. Llano,et al.  Spatial heterogeneity of intracellular Ca2+ signals in axons of basket cells from rat cerebellar slices , 1997, The Journal of physiology.

[35]  D. Protti,et al.  Calcium Currents and Calcium Signaling in Rod Bipolar Cells of Rat Retinal Slices , 1998, The Journal of Neuroscience.

[36]  D. Debanne,et al.  Long‐term synaptic plasticity between pairs of individual CA3 pyramidal cells in rat hippocampal slice cultures , 1998, The Journal of physiology.

[37]  E Neher,et al.  Fast scanning and efficient photodetection in a simple two-photon microscope , 1999, Journal of Neuroscience Methods.

[38]  M. Jackson,et al.  Passive current flow and morphology in the terminal arborizations of the posterior pituitary. , 1993, Journal of neurophysiology.

[39]  A. Marty,et al.  Control of interneurone firing pattern by axonal autoreceptors in the juvenile rat cerebellum , 2006, The Journal of physiology.

[40]  D. Durand,et al.  The somatic shunt cable model for neurons. , 1984, Biophysical journal.

[41]  D. Johnston,et al.  Active properties of neuronal dendrites. , 1996, Annual review of neuroscience.

[42]  N. Spruston,et al.  Determinants of Voltage Attenuation in Neocortical Pyramidal Neuron Dendrites , 1998, The Journal of Neuroscience.

[43]  Michael Häusser,et al.  Feed‐forward inhibition shapes the spike output of cerebellar Purkinje cells , 2005, The Journal of physiology.

[44]  Tiago Branco,et al.  The site of action potential initiation in cerebellar Purkinje neurons , 2005, Nature Neuroscience.

[45]  M. Scanziani,et al.  Enforcement of Temporal Fidelity in Pyramidal Cells by Somatic Feed-Forward Inhibition , 2001, Science.

[46]  Matteo Carandini,et al.  Somatosensory Integration Controlled by Dynamic Thalamocortical Feed-Forward Inhibition , 2005, Neuron.

[47]  B. Barbour.  Synaptic currents evoked in purkinje cells by stimulating individual granule cells , 1993, Neuron.

[48]  B. Sakmann,et al.  Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons , 1995, Neuron.

[49]  M B Jackson,et al.  Cable analysis with the whole-cell patch clamp. Theory and experiment. , 1992, Biophysical journal.

[50]  E E Fetz,et al.  Relation between shapes of post‐synaptic potentials and changes in firing probability of cat motoneurones , 1983, The Journal of physiology.

[51]  Y. Yarom,et al.  Jittery trains induced by synaptic-like currents in cerebellar inhibitory interneurons. , 2002, Journal of neurophysiology.

[52]  J. Eccles,et al.  The interpretation of spike potentials of motoneurones , 1957, The Journal of physiology.

[53]  Arnd Roth,et al.  Submillisecond AMPA Receptor-Mediated Signaling at a Principal Neuron–Interneuron Synapse , 1997, Neuron.

[54]  C. Pouzat,et al.  Somatic Recording of GABAergic Autoreceptor Current in Cerebellar Stellate and Basket Cells , 1999, The Journal of Neuroscience.

[55]  W Rall,et al.  Dendritic location of synapses and possible mechanisms for the monosynaptic EPSP in motoneurons. , 1967, Journal of neurophysiology.