Cognitive Neurodynamics

, Volume 8, Issue 4, pp 267–276 | Cite as

Input integration around the dendritic branches in hippocampal dentate granule cells

  • Tadanobu Chuyo Kamijo
  • Hirofumi Hayakawa
  • Yasuhiro Fukushima
  • Yoshiyuki Kubota
  • Yoshikazu Isomura
  • Minoru Tsukada
  • Takeshi Aihara
Research Article


Recent studies have shown that the dendrites of several neurons are not simple translators but are crucial facilitators of excitatory postsynaptic potential (EPSP) propagation and summation of synaptic inputs to compensate for inherent voltage attenuation. Granule cells (GCs)are located at the gateway for valuable information arriving at the hippocampus from the entorhinal cortex. However, the underlying mechanisms of information integration along the dendrites of GCs in the hippocampus are still unclear. In this study, we investigated the input integration around dendritic branches of GCs in the rat hippocampus. We applied differential spatiotemporal stimulations to the dendrites using a high-speed glutamate-uncaging laser. Our results showed that when two sites close to and equidistant from a branching point were simultaneously stimulated, a nonlinear summation of EPSPs was observed at the soma. In addition, nonlinear summation (facilitation) depended on the stimulus location and was significantly blocked by the application of a voltage-dependent Ca2+ channel antagonist. These findings suggest that the nonlinear summation of EPSPs around the dendritic branches of hippocampal GCs is a result of voltage-dependent Ca2+ channel activation and may play a crucial role in the integration of input information.


Hippocampus Dendrite Excitatory postsynaptic potentials summation Uncaging Supralinear amplification 



We thank Dr. Fujii of Yamagata Univ., Dr. Sakai of Tamagawa Univ., and Drs. Hong and Nishiyama of New York Univ. for valuable discussions and advice on the physiological experiments. This work was supported by the Global COE Program at Tamagawa University and Strategic Research Foundation for Private Universities and by NEXT KAKENHI Grants (Numbers 19200014 and 20500278).


  1. Alonso A, Klink R (1993) Differential electro responsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer II. J Neurophysiol 70(1):128–143PubMedGoogle Scholar
  2. Amaral DG, Scharfman HE, Lavenex P (2007) The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). Prog Brain Res 163:3–22. doi: 10.1016/S0079-6123(07)63001-5 PubMedCentralPubMedCrossRefGoogle Scholar
  3. Aradi I, Holmes WR (1999) Role of multiple calcium and calcium-dependent conductances in regulation of hippocampal dentate granule cell excitability. J Comput Neurosci 6(3):215–235PubMedCrossRefGoogle Scholar
  4. Branco T, Häusser M (2010) The single dendritic branch as a fundamental functional unit in the nervous system. Curr Opin Neurobiol 20(4):494–502. doi: 10.1016/j.conb.2010.07.009 PubMedCrossRefGoogle Scholar
  5. Branco T, Häusser M (2011) Synaptic integration gradients in single cortical pyramidal cell dendrites. Neuron 69(5):885–892. doi: 10.1016/j.neuron.2011.02.006 PubMedCrossRefGoogle Scholar
  6. Branco T, Clark BA, Häusser M (2010) Dendritic discrimination of temporal input sequences in cortical neurons. Science 329(5999):1671–1675. doi: 10.1126/science.1189664 PubMedCrossRefGoogle Scholar
  7. Buckmaster PS, Strowbridge BW, Kunkel DD, Schmiege DL, Schwartzkroin PA (1992) Mossy cell axonal projections to the dentate gyrus molecular layer in the rat hippocampal slice. Hippocampus 2(4):349–362. doi: 10.1002/hipo.450020403 PubMedCrossRefGoogle Scholar
  8. Buckmaster PS, Wenzel HJ, Kunkel DD, Schwartzkroin PA (1996) Axon arbors and synaptic connections of hippocampal mossy cells in the rat in vivo. J Comp Neurol 366(2):271–292PubMedCrossRefGoogle Scholar
  9. Claiborne BJ, Amaral DG, Cowan WM (1990) Quantitative, three-dimensional analysis of granule cell dendrites in the rat dentate gyrus. J Comp Neurol 302(2):206–219. doi: 10.1002/cne.903020203 PubMedCrossRefGoogle Scholar
  10. Fyhn M, Molden S, Witter MP, Moser EI, Moser MB (2004) Spatial representation in the entorhinal cortex. Science 305(5688):1258–1264. doi: 10.1126/science.1099901 PubMedCrossRefGoogle Scholar
  11. Hargreaves EL, Rao G, Lee I, Knierim JJ (2005) Major dissociation between medial and lateral entorhinal input to dorsal hippocampus. Science 308(5729):1792–1794. doi: 10.1126/science.1110449 PubMedCrossRefGoogle Scholar
  12. Hayman RM, Jeffery KJ (2008) How heterogeneous place cell responding arises from homogeneous grids—a contextual gating hypothesis. Hippocampus 18(12):1301–1313. doi: 10.1002/hipo.20513 PubMedCrossRefGoogle Scholar
  13. Jackson MB, Scharfman HE (1996) Positive feedback from hilar mossy cells to granule cells in the dentate gyrus revealed by voltage-sensitive dye and microelectrode recording. J Neurophysiol 76(1):601–616PubMedGoogle Scholar
  14. Jaffe DB, Carnevale NT (1999) Passive normalization of synaptic integration influenced by dendritic architecture. J Neurophysiol 82(6):3268–3285PubMedGoogle Scholar
  15. Jinde S, Zsiros V, Nakazawa K (2013) Hilar mossy cell circuitry controlling dentate granule cell excitability. Front Neural Circuits 7:14. doi: 10.3389/fncir.2013.00014 PubMedCentralPubMedCrossRefGoogle Scholar
  16. Kojima H (2006) Development of a system for patterned rapid photolysis and 2-photon confocal microscopy. Circuits Devices Mag IEEE 22:66–74CrossRefGoogle Scholar
  17. Krueppel R, Remy S, Beck H (2011) Dendritic integration in hippocampal dentate granule cells. Neuron 71(3):512–528. doi: 10.1016/j.neuron.2011.05.043 PubMedCrossRefGoogle Scholar
  18. Kubota Y, Karube F, Nomura M, Gulledge AT, Mochizuki A, Schertel A, Kawaguchi Y (2011) Conserved properties of dendritic trees in four cortical interneuron subtypes. Sci Rep 1:89. doi: 10.1038/srep00089 PubMedCentralPubMedCrossRefGoogle Scholar
  19. London M, Häusser M (2005) Dendritic computation. Annu Rev Neurosci 28:503–532. doi: 10.1146/annurev.neuro.28.061604.135703 PubMedCrossRefGoogle Scholar
  20. McRory JE, Santi CM, Hamming KS, Mezeyova J, Sutton KG, Baillie DL, Stea A, Snutch TP (2001) Molecular and functional characterization of a family of rat brain T-type calcium channels. J Biol Chem 276(6):3999–4011. doi: 10.1074/jbc.M008215200 PubMedCrossRefGoogle Scholar
  21. Nishimura-Akiyoshi S, Niimi K, Nakashiba T, Itohara S (2007) Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segments. Proc Natl Acad Sci USA 104(37):14801–14806. doi: 10.1073/pnas.0706919104 PubMedCentralPubMedCrossRefGoogle Scholar
  22. Rall W (1962) Electrophysiology of a dendritic neuron model. Biophys J 2(2 Pt 2):145–167PubMedCentralPubMedCrossRefGoogle Scholar
  23. Schmidt-Hieber C, Jonas P, Bischofberger J (2007) Subthreshold dendritic signal processing and coincidence detection in dentate gyrus granule cells. J Neurosci Off J Soc Neurosci 27(31):8430–8441. doi: 10.1523/JNEUROSCI.1787-07.2007 CrossRefGoogle Scholar
  24. Tahvildari B, Alonso A (2005) Morphological and electrophysiological properties of lateral entorhinal cortex layers II and III principal neurons. J Comp Neurol 491(2):123–140. doi: 10.1002/cne.20706 PubMedCrossRefGoogle Scholar
  25. Wang X, Lambert NA (2003) Membrane properties of identified lateral and medial perforant pathway projection neurons. Neuroscience 117(2):485–492. doi: 10.1016/s0306-4522(02)00659-0 PubMedCrossRefGoogle Scholar
  26. Yoganarasimha D, Rao G, Knierim JJ (2011) Lateral entorhinal neurons are not spatially selective in cue-rich environments. Hippocampus 21(12):1363–1374. doi: 10.1002/hipo.20839 PubMedCentralPubMedCrossRefGoogle Scholar
  27. Yoneyama M, Fukushima Y, Tsukada M, Aihara T (2011) Spatiotemporal characteristics of synaptic EPSP summation on the dendritic trees of hippocampal CA1 pyramidal neurons as revealed by laser uncaging stimulation. Cogn Neurodyn 5(4):333–342. doi: 10.1007/s11571-011-9158-9 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Tadanobu Chuyo Kamijo
    • 1
  • Hirofumi Hayakawa
    • 1
  • Yasuhiro Fukushima
    • 2
  • Yoshiyuki Kubota
    • 3
  • Yoshikazu Isomura
    • 1
  • Minoru Tsukada
    • 1
  • Takeshi Aihara
    • 1
  1. 1.Graduate School of Brain SciencesTamagawa UniversityMachidaJapan
  2. 2.Faculty of Health and WelfareKawasaki University of Medical WelfareKurashikiJapan
  3. 3.National Institute for Physiological ScienceOkazakiJapan

Personalised recommendations