Attenuation of backpropagating action potentials in three types of dentate granule cells

Yue Mao , Ming Liu , Xiaojuan Sun

Electronic Research Archive ›› 2025, Vol. 33 ›› Issue (9) : 5845 -5864.

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Electronic Research Archive ›› 2025, Vol. 33 ›› Issue (9) :5845 -5864. DOI: 10.3934/era.2025260
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Attenuation of backpropagating action potentials in three types of dentate granule cells
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Abstract

Backpropagating action potentials (bpAPs) are retrograde electrical signals crucial for modulating synaptic plasticity. They play a pivotal role in regulating neuronal computation and memory formation. In dentate gyrus granule cells, which are key neuronal populations responsible for pattern separation and memory storage, bpAPs-mediated signaling is particularly important for integrating synaptic inputs and fine-tuning network activity. However, this neuronal population has marked structural and functional heterogeneity, including regular granule cells (GCs), semilunar granule cells (SGCs), and hilar ectopic granule cells (HEGCs). The influence of the distinct biophysical properties of these GC subtypes on backpropagation dynamics such as attenuation amplitude, velocity, and spatial spread remains unclear. Here, we utilized multi-compartment models of three types of GCs to systematically investigate the backpropagation efficiency across three metrics: attenuation amplitude, attenuation rate, and propagation distance. We found that higher dendritic K+ channel density drove strong attenuation of bpAPs in SGCs (highest rate, shortest propagation), whereas higher dendritic Na+ channel density in HEGCs minimized attenuation. Dendritic branching patterns modulated attenuation amplitude secondarily, while passive axial resistance had negligible effects. These findings establish dendritic active properties rather than morphology as the dominant regulator of attenuation intensity and reveal how activity regulation in these neuronal subtypes contributes to pattern separation and memory storage.

Keywords

backpropagation / attenuation / granule cell / semilunar granule cell / hilar ectopic granule cell / dentate gyrus / multi-compartment model

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Yue Mao, Ming Liu, Xiaojuan Sun. Attenuation of backpropagating action potentials in three types of dentate granule cells. Electronic Research Archive, 2025, 33 (9) : 5845-5864 DOI:10.3934/era.2025260

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References

[1]

G. Stuart, N. Spruston, B. Sakmann, M. Häusser, Action potential initiation and backpropagation in neurons of the mammalian CNS, Trends Neurosci., 20 (1997), 125-131. https://doi.org/10.1016/s0166-2236(96)10075-8

[2]

P. Vetter, A. Roth, M. Häusser, Propagation of action potentials in dendrites depends on dendritic morphology, J. Neurophysiol., 85 (2001), 926-937. https://doi.org/10.1152/jn.2001.85.2.926

[3]

J. Brunner, J. Szabadics, Analogue modulation of back-propagating action potentials enables dendritic hybrid signalling, Nat. Commun., 7 (2016), 13033. https://doi.org/10.1038/ncomms13033

[4]

N. L. Golding, W. L. Kath, N. Spruston, Dichotomy of action-potential backpropagation in CA1 pyramidal neuron dendrites, J. Neurophysiol., 86 (2001), 2998-3010. https://doi.org/10.1152/jn.2001.86.6.2998

[5]

D. Johnston, J. C. Magee, C. M. Colbert, B. R. Christie, Active properties of neuronal dendrites, Annu. Rev. Neurosci., 19 (1996), 165-186. https://doi.org/10.1146/annurev.ne.19.030196.001121

[6]

T. Bock, A. Negrean, S. A. Siegelbaum, Somatic depolarization enhances hippocampal CA1 dendritic spike propagation and distal input driven synaptic plasticity, J. Neurosci., 42 (2022), 3406-3425. https://doi.org/10.1523/JNEUROSCI.0780-21.2022

[7]

C. Schmidt-Hieber, P. Jonas, J. Bischofberger, Subthreshold dendritic signal processing and coincidence detection in dentate gyrus granule cells, J. Neurosci., 27 (2007), 8430-8441. https://doi.org/10.1523/jneurosci.1787-07.2007

[8]

M. Häusser, G. Stuart, C. Racca, B. Sakmann, Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons, Neuron, 15 (1995), 637-647. https://doi.org/10.1016/0896-6273(95)90152-3

[9]

J. Waters, A. Schaefer, B. Sakmann, Backpropagating action potentials in neurones: Measurement, mechanisms and potential functions, Prog. Biophys. Mol. Biol., 87 (2005), 145-170. https://doi.org/10.1016/j.pbiomolbio.2004.06.009

[10]

O. Herreras, Propagating dendritic action potential mediates synaptic transmission in CA1 pyramidal cells in situ, J. Neurophysiol., 64 (1990), 1429-1441. https://doi.org/10.1152/jn.1990.64.5.1429

[11]

R. W. Turner, L. Maler, T. Deerinck, S. R. Levinson, M. H. Ellisman, TTX-sensitive dendritic sodium channels underlie oscillatory discharge in a vertebrate sensory neuron, J. Neurosci., 14 (1994), 6453-6471. https://doi.org/10.1523/jneurosci.14-11-06453.1994

[12]

W. Tian, L. Peng, M. Zhao, L. Tao, P. Zou, Y. Zhang, Dendritic morphology affects the velocity and amplitude of back-propagating action potentials, Neurosci. Bull., 38 (2022), 1330-1346. https://doi.org/10.1007/s12264-022-00931-9

[13]

T. Hainmueller, M. Bartos, Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories, Nat. Rev. Neurosci., 21 (2020), 153-168. https://doi.org/10.1038/s41583-019-0260-z

[14]

X. Zhang, P. Jonas, Integration of spatial and non-spatial information by heterogeneous dentate gyrus granule cells, J. Life Sci., 2 (2020), 19-24.

[15]

A. Gupta, A. Proddutur, Y. J. Chang, V. Raturi, J. Guevarra, Y. Shah, et al., Dendritic morphology and inhibitory regulation distinguish dentate semilunar granule cells from granule cells through distinct stages of postnatal development, Brain Struct. Funct., 225 (2020), 2841-2855. https://doi.org/10.1101/2019.12.17.880005

[16]

Y. Kasahara, H. Nakashima, K. Nakashima, Seizure-induced hilar ectopic granule cells in the adult dentate gyrus, Front. Neurosci., 17 (2023), 1150283. https://doi.org/10.3389/fnins.2023.1150283

[17]

Y. Mao, M. Liu, X. Sun, Excitatory synaptic integration of three types of granule cells in the dentate gyrus, Cognit. Neurodyn., 19 (2025), 40. https://doi.org/10.1007/s11571-025-10226-0

[18]

S. Chavlis, P. C. Petrantonakis, P. Poirazi, Dendrites of dentate gyrus granule cells contribute to pattern separation by controlling sparsity, Hippocampus, 27 (2017), 89-110. https://doi.org/10.1002/hipo.22675

[19]

S. Kim, Y. Kim, S. H. Lee, W. K. Ho, Dendritic spikes in hippocampal granule cells are necessary for long-term potentiation at the perforant path synapse, eLife, 7 (2018), e35269. https://doi.org/10.7554/eLife.35269

[20]

R. Krueppel, S. Remy, H. Beck, Dendritic integration in hippocampal dentate granule cells, Neuron, 71 (2011), 512-528. https://doi.org/10.1016/j.neuron.2011.05.043

[21]

M. Häusser, B. Mel, Dendrites: Bug or feature, Curr. Opin. Neurobiol., 13 (2003), 372-383. https://doi.org/10.1016/s0959-4388(03)00075-8

[22]

P. Jedlicka, L. Benuskova, W. C. Abraham, A voltage-based STDP rule combined with fast BCM-like metaplasticity accounts for LTP and concurrent “heterosynaptic” LTD in the dentate gyrus in vivo, PLoS Comput. Biol., 11 (2015), e1004588. https://doi.org/10.1371/journal.pcbi.1004588

[23]

H. Yin, X. Sun, K. Yang, Y. Lan, Z. Lu, Regulation of dentate gyrus pattern separation by hilus ectopic granule cells, Cognit. Neurodyn., 19 (2025), 10. https://doi.org/10.1007/s11571-024-10204-y

[24]

M. L. Hines, N. T. Carnevale, NEURON: A tool for neuroscientists, Neuroscientist, 7 (2001), 123-135. https://doi.org/10.1177/107385840100700207

[25]

K. R. Kim, S. Y. Lee, S. H. Yoon, Y. Kim, H. J. Jeong, S. Lee, et al., Kv4.1, a key ion channel for low frequency firing of dentate granule cells, is crucial for pattern separation, J. Neurosci., 40 (2020), 2200-2214. https://doi.org/10.1523/JNEUROSCI.1541-19.2020

[26]

N. L. Golding, T. J. Mickus, Y. Katz, W. L. Kath, N. Spruston, Factors mediating powerful voltage attenuation along CA1 pyramidal neuron dendrites, J. Physiol., 568 (2005), 69-82. https://doi.org/10.1113/jphysiol.2005.086793

[27]

J. H. Goldberg, G. Tamas, R. Yuste, Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation , J. Physiol., 551 (2003), 49-65. https://doi.org/10.1113/jphysiol.2003.042580

[28]

H. Y. Jung, T. Mickus, N. Spruston, Prolonged sodium channel inactivation contributes to dendritic action potential attenuation in hippocampal pyramidal neurons, J. Neurosci., 17 (1997), 6639-6646. https://doi.org/10.1523/JNEUROSCI.17-17-06639.1997

[29]

Z. He, S. Zhang, Q. Song, W. Li, D. Liu, H. Li, et al., The structural development of primary cultured hippocampal neurons on a graphene substrate, Colloids Surf. B Biointerfaces, 146 (2016), 442-451. https://doi.org/10.1016/j.colsurfb.2016.06.045

[30]

M. Diamantaki, M. Frey, P. Berens, P. Preston-Ferrer, A. Burgalossi, Sparse activity of identified dentate granule cells during spatial exploration, eLife, 5 (2016), e20252. https://doi.org/10.7554/elife.20252

[31]

S. S. Goldstein, W. Rall, Changes of action potential shape and velocity for changing core conductor geometry, Biophys. J., 14 (1974), 731-757. https://doi.org/10.1016/s0006-3495(74)85947-3

[32]

C. D. Acker, J. A. White, Roles of IA and morphology in action potential propagation in CA1 pyramidal cell dendrites, J. Comput. Neurosci., 23 (2007), 201-216. https://doi.org/10.1007/s10827-007-0028-8

[33]

W. Rall, Branching dendritic trees and motoneuron membrane resistivity, Exp. Neurol., 1 (1959), 491-527. https://doi.org/10.1016/0014-4886(59)90046-9

[34]

V. Volman, H. Levine, T. J. Sejnowski, Shunting inhibition controls the gain modulation mediated by asynchronous neurotransmitter release in early development, PLoS Comput. Biol., 6 (2010), e1000973. https://doi.org/10.1371/journal.pcbi.1000973

[35]

K. Yang, X. Sun, S. Zhu, The heterogeneous population of granule cells contributes to pattern separation of the dentate gyrus neural network, Nonlinear Dyn., 112 (2024), 13465-13481. https://doi.org/10.1007/s11071-024-09730-5

[36]

M. Y. Yim, A. Hanuschkin, J. Wolfart, Intrinsic rescaling of granule cells restores pattern separation ability of a dentate gyrus network model during epileptic hyperexcitability, Hippocampus, 25 (2015), 297-308. https://doi.org/10.1002/hipo.22373

[37]

L. Dovek, K. Marrero, E. Zagha, V. Santhakumar, Cellular and circuit features distinguish dentate gyrus semilunar granule cells and granule cells activated during contextual memory formation, eLife, 14 (2025), e101428. https://doi.org/10.1101/2024.08.21.608983

[38]

R. Z. Zhan, J. V. Nadler, Enhanced tonic GABA current in normotopic and hilar ectopic dentate granule cells after pilocarpine-induced status epilepticus, J. Neurophysiol., 102 (2009), 670-681. https://doi.org/10.1152/jn.00147.2009

[39]

M. C. Cameron, R. Zhan, J. V. Nadler, Morphologic integration of hilar ectopic granule cells into dentate gyrus circuitry in the pilocarpine model of temporal lobe epilepsy, J. Comp. Neurol., 519 (2011), 2175-2192. https://doi.org/10.1002/cne.22623

[40]

J. N. Wood, J. P. Boorman, K. Okuse, M. D. Baker, Voltage-gated sodium channels and pain pathways, J. Neurobiol., 61 (2004), 55-71. https://doi.org/10.1002/neu.20094

[41]

D. Johnston, D. A. Hoffman, J. C. Magee, N. P. Poolos, S. Watanabe, C. M. Colbert, et al., Dendritic potassium channels in hippocampal pyramidal neurons, J. Physiol., 525 (2000), 75-81. https://doi.org/10.1111/j.1469-7793.2000.00075.x

[42]

A. J. Hudspeth, M. M. Poo, A. E. Stuart, Passive signal propagation and membrane properties in median photoreceptors of the giant barnacle, J. Physiol., 272 (1977), 25-43. https://doi.org/10.1113/jphysiol.1977.sp012032

[43]

P. Alcami, A. El Hady, Axonal computations, Front. Cell Neurosci., 13 (2019), 413. https://doi.org/10.3389/fncel.2019.00413

[44]

N. Spruston, Pyramidal neurons: Dendritic structure and synaptic integration, Nat. Rev. Neurosci., 9 (2008), 206-221. https://doi.org/10.1038/nrn2286

[45]

J. Tønnesen, G. Katona, B. Rózsa, U. V. Nägerl, Spine neck plasticity regulates compartmentalization of synapses, Nat. Neurosci., 17 (2014), 678-685. https://doi.org/10.1038/nn.3682

[46]

A. L. Althaus, S. J. Moore, H. Zhang, X. Du, G. G. Murphy, J. M. Parent, Altered synaptic drive onto birthdated dentate granule cells in experimental temporal lobe epilepsy, J. Neurosci., 39 (2019), 7604-7614. https://doi.org/10.1523/JNEUROSCI.0654-18.2019

[47]

S. C. Danzer, Adult neurogenesis in the development of epilepsy, Epilepsy Curr., 19 (2019), 316-320. https://doi.org/10.1177/1535759719868186

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