Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 311 (5765): 1290-1293

Copyright © 2006 by the American Association for the Advancement of Science

Combined Analog and Action Potential Coding in Hippocampal Mossy Fibers

Henrik Alle, and Jörg R. P. Geiger*

Abstract: In the mammalian cortex, it is generally assumed that the output information of neurons is encoded in the number and the timing of action potentials. Here, we show, by using direct patchclamp recordings from presynaptic hippocampal mossy fiber boutons, that axons transmit analog signals in addition to action potentials. Excitatory presynaptic potentials result from subthreshold dendritic synaptic inputs, which propagate several hundreds of micrometers along the axon and modulate action potential–evoked transmitter release at the mossy fiber–CA3 synapse. This combined analog and action potential coding represents an additional mechanism for information transmission in a major hippocampal pathway.

Independent Hertie Research Group, Max Planck Institute for Brain Research, D-60528 Frankfurt, Germany.

* To whom correspondence should be addressed. E-mail: geiger{at}

Activation of Axonal Receptors by GABA Spillover Increases Somatic Firing.
J. R. Pugh and C. E. Jahr (2013)
J. Neurosci. 33, 16924-16929
   Abstract »    Full Text »    PDF »
GnRH Neurons Elaborate a Long-Range Projection with Shared Axonal and Dendritic Functions.
M. K. Herde, K. J. Iremonger, S. Constantin, and A. E. Herbison (2013)
J. Neurosci. 33, 12689-12697
   Abstract »    Full Text »    PDF »
Dopaminergic modulation of axonal potassium channels and action potential waveform in pyramidal neurons of prefrontal cortex.
J. Yang, M. Ye, C. Tian, M. Yang, Y. Wang, and Y. Shu (2013)
J. Physiol. 591, 3233-3251
   Abstract »    Full Text »    PDF »
Matching Recall and Storage in Sequence Learning with Spiking Neural Networks.
J. Brea, W. Senn, and J.-P. Pfister (2013)
J. Neurosci. 33, 9565-9575
   Abstract »    Full Text »    PDF »
Differential GABAB-Receptor-Mediated Effects in Perisomatic- and Dendrite-Targeting Parvalbumin Interneurons.
S. A. Booker, A. Gross, D. Althof, R. Shigemoto, B. Bettler, M. Frotscher, M. Hearing, K. Wickman, M. Watanabe, A. Kulik, et al. (2013)
J. Neurosci. 33, 7961-7974
   Abstract »    Full Text »    PDF »
Selective Silencing of Individual Dendritic Branches by an mGlu2-Activated Potassium Conductance in Dentate Gyrus Granule Cells.
J. Brunner, J. Ster, S. Van-Weert, T. Andrasi, M. Neubrandt, C. Corti, M. Corsi, F. Ferraguti, U. Gerber, and J. Szabadics (2013)
J. Neurosci. 33, 7285-7298
   Abstract »    Full Text »    PDF »
Calcium-Dependent Isoforms of Protein Kinase C Mediate Glycine-Induced Synaptic Enhancement at the Calyx of Held.
Y. Chu, D. Fioravante, M. Thanawala, M. Leitges, and W. G. Regehr (2012)
J. Neurosci. 32, 13796-13804
   Abstract »    Full Text »    PDF »
Heterogeneity and independency of unitary synaptic outputs from hippocampal CA3 pyramidal cells.
T. Sasaki, N. Matsuki, and Y. Ikegaya (2012)
J. Physiol. 590, 4869-4880
   Abstract »    Full Text »    PDF »
Segregation of Axonal and Somatic Activity During Fast Network Oscillations.
T. Dugladze, D. Schmitz, M. A. Whittington, I. Vida, and T. Gloveli (2012)
Science 336, 1458-1461
   Abstract »    Full Text »    PDF »
Effects of Axonal Topology on the Somatic Modulation of Synaptic Outputs.
T. Sasaki, N. Matsuki, and Y. Ikegaya (2012)
J. Neurosci. 32, 2868-2876
   Abstract »    Full Text »    PDF »
Neural Representations of Courtship Song in the Drosophila Brain.
S. Tootoonian, P. Coen, R. Kawai, and M. Murthy (2012)
J. Neurosci. 32, 787-798
   Abstract »    Full Text »    PDF »
GABA Is Depolarizing in Hippocampal Dentate Granule Cells of the Adolescent and Adult Rats.
P.-H. Chiang, P.-Y. Wu, T.-W. Kuo, Y.-C. Liu, C.-F. Chan, T.-C. Chien, J.-K. Cheng, Y.-Y. Huang, C.-D. Chiu, and C.-C. Lien (2012)
J. Neurosci. 32, 62-67
   Abstract »    Full Text »    PDF »
The Energetics of CNS White Matter.
J. J. Harris and D. Attwell (2012)
J. Neurosci. 32, 356-371
   Abstract »    Full Text »    PDF »
NMDA Receptor Agonists Fail To Alter Release from Cerebellar Basket Cells.
J. R. Pugh and C. E. Jahr (2011)
J. Neurosci. 31, 16550-16555
   Abstract »    Full Text »    PDF »
Somatic Membrane Potential and Kv1 Channels Control Spike Repolarization in Cortical Axon Collaterals and Presynaptic Boutons.
A. J. Foust, Y. Yu, M. Popovic, D. Zecevic, and D. A. McCormick (2011)
J. Neurosci. 31, 15490-15498
   Abstract »    Full Text »    PDF »
Ivy and Neurogliaform Interneurons Are a Major Target of {micro}-Opioid Receptor Modulation.
E. Krook-Magnuson, L. Luu, S.-H. Lee, C. Varga, and I. Soltesz (2011)
J. Neurosci. 31, 14861-14870
   Abstract »    Full Text »    PDF »
Peptide Neuromodulation of Synaptic Dynamics in an Oscillatory Network.
S. Zhao, A. F. Sheibanie, M. Oh, P. Rabbah, and F. Nadim (2011)
J. Neurosci. 31, 13991-14004
   Abstract »    Full Text »    PDF »
Effect of presynaptic membrane potential on electrical vs. chemical synaptic transmission.
C. G. Evans, B. C. Ludwar, T. Kang, and E. C. Cropper (2011)
J Neurophysiol 106, 680-689
   Abstract »    Full Text »    PDF »
Effect of Holding Potential on the Dynamics of Homosynaptic Facilitation.
C. G. Evans, B. C. Ludwar, J. Askanas, and E. C. Cropper (2011)
J. Neurosci. 31, 11039-11043
   Abstract »    Full Text »    PDF »
Biphasic action of axonal GABA-A receptors on presynaptic calcium influx.
B. M. Stell (2011)
J Neurophysiol 105, 2931-2936
   Abstract »    Full Text »    PDF »
Sparse But Highly Efficient Kv3 Outpace BKCa Channels in Action Potential Repolarization at Hippocampal Mossy Fiber Boutons.
H. Alle, H. Kubota, and J. R. P. Geiger (2011)
J. Neurosci. 31, 8001-8012
   Abstract »    Full Text »    PDF »
Somatic Depolarization Enhances GABA Release in Cerebellar Interneurons via a Calcium/Protein Kinase C Pathway.
B. Bouhours, F. F. Trigo, and A. Marty (2011)
J. Neurosci. 31, 5804-5815
   Abstract »    Full Text »    PDF »
Axon Physiology.
D. Debanne, E. Campanac, A. Bialowas, E. Carlier, and G. Alcaraz (2011)
Physiol Rev 91, 555-602
   Abstract »    Full Text »    PDF »
Astrocytes Shape Axonal Signaling.
D. Debanne and S. Rama (2011)
Science Signaling 4, pe11
   Abstract »    Full Text »    PDF »
Action-Potential Modulation During Axonal Conduction.
T. Sasaki, N. Matsuki, and Y. Ikegaya (2011)
Science 331, 599-601
   Abstract »    Full Text »    PDF »
Morphological and electrical properties of oligodendrocytes in the white matter of the corpus callosum and cerebellum.
Y. Bakiri, R. Karadottir, L. Cossell, and D. Attwell (2011)
J. Physiol. 589, 559-573
   Abstract »    Full Text »    PDF »
Axonal GABAA Receptors Increase Cerebellar Granule Cell Excitability and Synaptic Activity.
J. R. Pugh and C. E. Jahr (2011)
J. Neurosci. 31, 565-574
   Abstract »    Full Text »    PDF »
P/Q and N Channels Control Baseline and Spike-Triggered Calcium Levels in Neocortical Axons and Synaptic Boutons.
Y. Yu, C. Maureira, X. Liu, and D. McCormick (2010)
J. Neurosci. 30, 11858-11869
   Abstract »    Full Text »    PDF »
Granule Cells in the CA3 Area.
J. Szabadics, C. Varga, J. Brunner, K. Chen, and I. Soltesz (2010)
J. Neurosci. 30, 8296-8307
   Abstract »    Full Text »    PDF »
The Sushi Domains of GABAB Receptors Function as Axonal Targeting Signals.
B. Biermann, K. Ivankova-Susankova, A. Bradaia, S. Abdel Aziz, V. Besseyrias, J. P. Kapfhammer, M. Missler, M. Gassmann, and B. Bettler (2010)
J. Neurosci. 30, 1385-1394
   Abstract »    Full Text »    PDF »
Atypical Functional Properties of GluK3-Containing Kainate Receptors.
D. Perrais, F. Coussen, and C. Mulle (2009)
J. Neurosci. 29, 15499-15510
   Abstract »    Full Text »    PDF »
Selective Expression of Ligand-Gated Ion Channels in L5 Pyramidal Cell Axons.
J. M. Christie and C. E. Jahr (2009)
J. Neurosci. 29, 11441-11450
   Abstract »    Full Text »    PDF »
Energy-Efficient Action Potentials in Hippocampal Mossy Fibers.
H. Alle, A. Roth, and J. R. P. Geiger (2009)
Science 325, 1405-1408
   Abstract »    Full Text »    PDF »
Two Distinct Mechanisms Mediate Potentiating Effects of Depolarization on Synaptic Transmission.
B. Ch. Ludwar, C. G. Evans, J. Jing, and E. C. Cropper (2009)
J Neurophysiol 102, 1976-1983
   Abstract »    Full Text »    PDF »
Mechanisms underlying short-term modulation of transmitter release by presynaptic depolarization.
T. Hori and T. Takahashi (2009)
J. Physiol. 587, 2987-3000
   Abstract »    Full Text »    PDF »
Subthreshold Glutamate Release from Mitral Cell Dendrites.
J. B. Castro and N. N. Urban (2009)
J. Neurosci. 29, 7023-7030
   Abstract »    Full Text »    PDF »
System A Transporter SAT2 Mediates Replenishment of Dendritic Glutamate Pools Controlling Retrograde Signaling by Glutamate.
M. Jenstad, A. Z. Quazi, M. Zilberter, C. Haglerod, P. Berghuis, N. Saddique, M. Goiny, D. Buntup, S. Davanger, F.-M. S. Haug, et al. (2009)
Cereb Cortex 19, 1092-1106
   Abstract »    Full Text »    PDF »
The GABAB1a Isoform Mediates Heterosynaptic Depression at Hippocampal Mossy Fiber Synapses.
N. Guetg, R. Seddik, R. Vigot, R. Turecek, M. Gassmann, K. E. Vogt, H. Brauner-Osborne, R. Shigemoto, O. Kretz, M. Frotscher, et al. (2009)
J. Neurosci. 29, 1414-1423
   Abstract »    Full Text »    PDF »
Target-Cell Specificity of Kainate Autoreceptor and Ca2+-Store-Dependent Short-Term Plasticity at Hippocampal Mossy Fiber Synapses.
R. Scott, T. Lalic, D. M. Kullmann, M. Capogna, and D. A. Rusakov (2008)
J. Neurosci. 28, 13139-13149
   Abstract »    Full Text »    PDF »
Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus.
J. F. Atherton, D. L. Wokosin, S. Ramanathan, and M. D. Bevan (2008)
J. Physiol. 586, 5679-5700
   Abstract »    Full Text »    PDF »
Analog Modulation of Mossy Fiber Transmission Is Uncoupled from Changes in Presynaptic Ca2+.
R. Scott, A. Ruiz, C. Henneberger, D. M. Kullmann, and D. A. Rusakov (2008)
J. Neurosci. 28, 7765-7773
   Abstract »    Full Text »    PDF »
High Threshold, Proximal Initiation, and Slow Conduction Velocity of Action Potentials in Dentate Granule Neuron Mossy Fibers.
G. J. Kress, M. J. Dowling, J. P. Meeks, and S. Mennerick (2008)
J Neurophysiol 100, 281-291
   Abstract »    Full Text »    PDF »
GABAergic Depolarization of the Axon Initial Segment in Cortical Principal Neurons Is Caused by the Na-K-2Cl Cotransporter NKCC1.
S. Khirug, J. Yamada, R. Afzalov, J. Voipio, L. Khiroug, and K. Kaila (2008)
J. Neurosci. 28, 4635-4639
   Abstract »    Full Text »    PDF »
Dendritic Excitability and Synaptic Plasticity.
P. J. Sjostrom, E. A. Rancz, A. Roth, and M. Hausser (2008)
Physiol Rev 88, 769-840
   Abstract »    Full Text »    PDF »
Action potential initiation and propagation in hippocampal mossy fibre axons.
C. Schmidt-Hieber, P. Jonas, and J. Bischofberger (2008)
J. Physiol. 586, 1849-1857
   Abstract »    Full Text »    PDF »
Action Potential-Independent and Nicotinic Receptor-Mediated Concerted Release of Multiple Quanta at Hippocampal CA3-Mossy Fiber Synapses.
G. Sharma, M. Grybko, and S. Vijayaraghavan (2008)
J. Neurosci. 28, 2563-2575
   Abstract »    Full Text »    PDF »
Synapse-Specific Expression of Functional Presynaptic NMDA Receptors in Rat Somatosensory Cortex.
D. J. Brasier and D. E. Feldman (2008)
J. Neurosci. 28, 2199-2211
   Abstract »    Full Text »    PDF »
Pathway-specific use-dependent dynamics of excitatory synaptic transmission in rat intracortical circuits.
S. R. Williams and S. E. Atkinson (2007)
J. Physiol. 585, 759-777
   Abstract »    Full Text »    PDF »
Differential Gating and Recruitment of P/Q-, N-, and R-Type Ca2+ Channels in Hippocampal Mossy Fiber Boutons.
L. Li, J. Bischofberger, and P. Jonas (2007)
J. Neurosci. 27, 13420-13429
   Abstract »    Full Text »    PDF »
Synaptic Connections between Layer 5B Pyramidal Neurons in Mouse Somatosensory Cortex Are Independent of Apical Dendrite Bundling.
P. Krieger, T. Kuner, and B. Sakmann (2007)
J. Neurosci. 27, 11473-11482
   Abstract »    Full Text »    PDF »
Structural Determinants of Transmission at Large Hippocampal Mossy Fiber Synapses.
A. Rollenhagen, K. Satzler, E. P. Rodriguez, P. Jonas, M. Frotscher, and J. H. R. Lubke (2007)
J. Neurosci. 27, 10434-10444
   Abstract »    Full Text »    PDF »
Activation of Presynaptic GABAA Receptors Induces Glutamate Release from Parallel Fiber Synapses.
B. M. Stell, P. Rostaing, A. Triller, and A. Marty (2007)
J. Neurosci. 27, 9022-9031
   Abstract »    Full Text »    PDF »
Subthreshold Dendritic Signal Processing and Coincidence Detection in Dentate Gyrus Granule Cells.
C. Schmidt-Hieber, P. Jonas, and J. Bischofberger (2007)
J. Neurosci. 27, 8430-8441
   Abstract »    Full Text »    PDF »
Selective control of cortical axonal spikes by a slowly inactivating K+ current.
Y. Shu, Y. Yu, J. Yang, and D. A. McCormick (2007)
PNAS 104, 11453-11458
   Abstract »    Full Text »    PDF »
Action Potential Initiation and Propagation in CA3 Pyramidal Axons.
J. P. Meeks and S. Mennerick (2007)
J Neurophysiol 97, 3460-3472
   Abstract »    Full Text »    PDF »
Synapses in the Fly Motion-Vision Pathway: Evidence for a Broad Range of Signal Amplitudes and Dynamics.
U. Beckers, M. Egelhaaf, and R. Kurtz (2007)
J Neurophysiol 97, 2032-2041
   Abstract »    Full Text »    PDF »
GABAergic Spill-Over Transmission onto Hippocampal Mossy Fiber Boutons.
H. Alle and J. R. P. Geiger (2007)
J. Neurosci. 27, 942-950
   Abstract »    Full Text »    PDF »
Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings.
Y. Shu, A. Duque, Y. Yu, B. Haider, and D. A. McCormick (2007)
J Neurophysiol 97, 746-760
   Abstract »    Full Text »    PDF »
Electrophysiological Mechanisms of Delayed Excitotoxicity: Positive Feedback Loop Between NMDA Receptor Current and Depolarization-Mediated Glutamate Release.
C. M. Norris, E. M. Blalock, O. Thibault, L. D. Brewer, G. V. Clodfelter, N. M. Porter, and P. W. Landfield (2006)
J Neurophysiol 96, 2488-2500
   Abstract »    Full Text »    PDF »
Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release.
K. Vervaeke, N. Gu, C. Agdestein, H. Hu, and J. F. Storm (2006)
J. Physiol. 576, 235-256
   Abstract »    Full Text »    PDF »
Main determinants of presynaptic Ca2+ dynamics at individual mossy fiber-CA3 pyramidal cell synapses..
R. Scott and D. A. Rusakov (2006)
J. Neurosci. 26, 7071-7081
   Abstract »    Full Text »    PDF »
Analogue brains.
W. A. Wells (2006)
J. Cell Biol. 172, 958
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882