Main Article Content
Abstract
A reduced conductance-based model was assessed through somatic excitability, firing dynamics, and dendritic conductance responses. The reported baseline spike had a threshold of −36.5 mV, a baseline-to-peak amplitude of 115.1 mV, and a half-width of 0.93 ms. At 8 µA/cm², ISIs shortened before lengthening by 17.8% relative to the minimum interval. Dendritic A-current blockade increased amplitude from 92.8 to 100.8 mV, and halving dendritic Na⁺ conductance reduced it to 69.9 mV. Two new numerical experiments used a complete reference implementation with published channel kinetics. Joint waveform retuning reduced the normalized feature error by 84.7%, shifting the threshold from -39.13 to -49.36 mV and the amplitude from 114.71 to 96.76 mV. Matched zero-M and increased-M controls linked M-gate availability to late ISI lengthening, while a fixed A-inactivation gate changed the early-interval trajectory. The reported and reference baselines use their respective specified kinetics. These analyses quantify waveform trade-offs and conductance-dependent firing in the compact representation.
Keywords
Article Details
References
- Hodgkin, A. L., & Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. The Journal of Physiology, 117(4), 500–544. https://doi.org/10.1113/jphysiol.1952.sp004764
- Pinsky, P. F., & Rinzel, J. (1994). Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. Journal of Computational Neuroscience, 1(1–2), 39–60. https://doi.org/10.1007/BF00962717
- Traub, R. D., & Miles, R. (1991). Neuronal Networks of the Hippocampus. Cambridge University Press. https://doi.org/10.1017/CBO9780511895401
- Traub, R. D., Wong, R. K. S., Miles, R., & Michelson, H. (1991). A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances. Journal of Neurophysiology, 66(2), 635–650. https://doi.org/10.1152/jn.1991.66.2.635
- Hoffman, D. A., Magee, J. C., Colbert, C. M., & Johnston, D. (1997). K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature, 387(6636), 869–875. https://doi.org/10.1038/43119
- Spruston, N., Schiller, Y., Stuart, G., & Sakmann, B. (1995). Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science, 268(5208), 297–300. https://doi.org/10.1126/science.7716524
- Stuart, G. J., Spruston, N., Sakmann, B., & Häusser, M. (1997). Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends in Neurosciences, 20(3), 125–131. https://doi.org/10.1016/S0166-2236(96)10075-8
- Magee, J. C., & Johnston, D. (1995). Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science, 268(5208), 301–304. https://doi.org/10.1126/science.7716525
- Golding, N. L., Kath, W. L., & Spruston, N. (2001). Dichotomy of action-potential backpropagation in CA1 pyramidal neuron dendrites. Journal of Neurophysiology, 86(6), 2998–3010. https://doi.org/10.1152/jn.2001.86.6.2998
- Jarsky, T., Roxin, A., Kath, W. L., & Spruston, N. (2005). Conditional dendritic spike propagation following distal synaptic activation of hippocampal CA1 pyramidal neurons. Nature Neuroscience, 8(12), 1667–1676. https://doi.org/10.1038/nn1599
- Madison, D. V., & Nicoll, R. A. (1984). Control of the repetitive discharge of rat CA1 pyramidal neurones in vitro. The Journal of Physiology, 354, 319–331. https://doi.org/10.1113/jphysiol.1984.sp015378
- Bianchi, D., Marasco, A., Limongiello, A., Marchetti, C., Marie, H., Tirozzi, B., & Migliore, M. (2012). On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons. Journal of Computational Neuroscience, 33(2), 207–225. https://doi.org/10.1007/s10827-012-0383-y
- Pospischil, M., Toledo-Rodriguez, M., Monier, C., Piwkowska, Z., Bal, T., Frégnac, Y., Markram, H., & Destexhe, A. (2008). Minimal Hodgkin-Huxley type models for different classes of cortical and thalamic neurons. Biological Cybernetics, 99(4–5), 427–441. https://doi.org/10.1007/s00422-008-0263-8
- Migliore, M., Hoffman, D. A., Magee, J. C., & Johnston, D. (1999). Role of an A-type K+ conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons. Journal of Computational Neuroscience, 7(1), 5–15. https://doi.org/10.1023/A:1008906225285
- Sáray, S., Rössert, C. A., Appukuttan, S., Migliore, R., Vitale, P., Lupascu, C. A., Bologna, L. L., Van Geit, W., Romani, A., Davison, A. P., Muller, E., Freund, T. F., & Káli, S. (2021). HippoUnit: A software tool for the automated testing and systematic comparison of detailed models of hippocampal neurons based on electrophysiological data. PLOS Computational Biology, 17(1), e1008114. https://doi.org/10.1371/journal.pcbi.1008114
- Tomko, M., Benuskova, L., & Jedlicka, P. (2021). A new reduced-morphology model for CA1 pyramidal cells and its validation and comparison with other models using HippoUnit. Scientific Reports, 11, 7615. https://doi.org/10.1038/s41598-021-87002-7
- Appukuttan, S., & Davison, A. P. (2022). Reproducing and quantitatively validating a biologically-constrained point-neuron model of CA1 pyramidal cells. Frontiers in Integrative Neuroscience, 16, 1041423. https://doi.org/10.3389/fnint.2022.1041423
- Bock, T., Negrean, A., & Siegelbaum, S. A. (2022). Somatic depolarization enhances hippocampal CA1 dendritic spike propagation and distal input-driven synaptic plasticity. The Journal of Neuroscience, 42(16), 3406–3425. https://doi.org/10.1523/JNEUROSCI.0780-21.2022
- Pagkalos, M., Chavlis, S., & Poirazi, P. (2023). Introducing the Dendrify framework for incorporating dendrites to spiking neural networks. Nature Communications, 14, 131. https://doi.org/10.1038/s41467-022-35747-8
- Marasco, A., Tribuzi, C., Lupascu, C. A., & Migliore, M. (2024). Modeling realistic synaptic inputs of CA1 hippocampal pyramidal neurons and interneurons via Adaptive Generalized Leaky Integrate-and-Fire models. Mathematical Biosciences, 372, 109192. https://doi.org/10.1016/j.mbs.2024.109192
- Golomb, D., Yue, C., & Yaari, Y. (2006). Contribution of persistent Na+ current and M-type K+ current to somatic bursting in CA1 pyramidal cells: combined experimental and modeling study. Journal of Neurophysiology, 96(4), 1912–1926. https://doi.org/10.1152/jn.00205.2006
- Hines, M. L., & Carnevale, N. T. (1997). The NEURON simulation environment. Neural Computation, 9(6), 1179–1209. https://doi.org/10.1162/neco.1997.9.6.1179
- Hines, M. L., & Carnevale, N. T. (2001). NEURON: a tool for neuroscientists. The Neuroscientist, 7(2), 123–135. https://doi.org/10.1177/107385840100700207
- Carnevale, N. T., & Hines, M. L. (2006). The NEURON Book. Cambridge University Press. https://doi.org/10.1017/CBO9780511541612
- Spruston, N. (2008). Pyramidal neurons: dendritic structure and synaptic integration. Nature Reviews Neuroscience, 9(3), 206–221. https://doi.org/10.1038/nrn2286
- Andreasen, M., & Lambert, J. D. C. (1995). Regenerative properties of pyramidal cell dendrites in area CA1 of the rat hippocampus. The Journal of Physiology, 483(2), 421–441. https://doi.org/10.1113/jphysiol.1995.sp020595
- Gasparini, S., Migliore, M., & Magee, J. C. (2004). On the initiation and propagation of dendritic spikes in CA1 pyramidal neurons. The Journal of Neuroscience, 24(49), 11046–11056. https://doi.org/10.1523/JNEUROSCI.2520-04.2004
- Poirazi, P., Brannon, T., & Mel, B. W. (2003a). Pyramidal neuron as two-layer neural network. Neuron, 37(6), 989–999. https://doi.org/10.1016/S0896-6273(03)00149-1
- Poirazi, P., Brannon, T., & Mel, B. W. (2003b). Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron, 37(6), 977–987. https://doi.org/10.1016/S0896-6273(03)00148-X
- Colbert, C. M., Magee, J. C., Hoffman, D. A., & Johnston, D. (1997). Slow recovery from inactivation of Na+ channels underlies the activity-dependent attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons. The Journal of Neuroscience, 17(17), 6512–6521. https://doi.org/10.1523/JNEUROSCI.17-17-06512.1997
References
Hodgkin, A. L., & Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. The Journal of Physiology, 117(4), 500–544. https://doi.org/10.1113/jphysiol.1952.sp004764
Pinsky, P. F., & Rinzel, J. (1994). Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. Journal of Computational Neuroscience, 1(1–2), 39–60. https://doi.org/10.1007/BF00962717
Traub, R. D., & Miles, R. (1991). Neuronal Networks of the Hippocampus. Cambridge University Press. https://doi.org/10.1017/CBO9780511895401
Traub, R. D., Wong, R. K. S., Miles, R., & Michelson, H. (1991). A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances. Journal of Neurophysiology, 66(2), 635–650. https://doi.org/10.1152/jn.1991.66.2.635
Hoffman, D. A., Magee, J. C., Colbert, C. M., & Johnston, D. (1997). K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature, 387(6636), 869–875. https://doi.org/10.1038/43119
Spruston, N., Schiller, Y., Stuart, G., & Sakmann, B. (1995). Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science, 268(5208), 297–300. https://doi.org/10.1126/science.7716524
Stuart, G. J., Spruston, N., Sakmann, B., & Häusser, M. (1997). Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends in Neurosciences, 20(3), 125–131. https://doi.org/10.1016/S0166-2236(96)10075-8
Magee, J. C., & Johnston, D. (1995). Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science, 268(5208), 301–304. https://doi.org/10.1126/science.7716525
Golding, N. L., Kath, W. L., & Spruston, N. (2001). Dichotomy of action-potential backpropagation in CA1 pyramidal neuron dendrites. Journal of Neurophysiology, 86(6), 2998–3010. https://doi.org/10.1152/jn.2001.86.6.2998
Jarsky, T., Roxin, A., Kath, W. L., & Spruston, N. (2005). Conditional dendritic spike propagation following distal synaptic activation of hippocampal CA1 pyramidal neurons. Nature Neuroscience, 8(12), 1667–1676. https://doi.org/10.1038/nn1599
Madison, D. V., & Nicoll, R. A. (1984). Control of the repetitive discharge of rat CA1 pyramidal neurones in vitro. The Journal of Physiology, 354, 319–331. https://doi.org/10.1113/jphysiol.1984.sp015378
Bianchi, D., Marasco, A., Limongiello, A., Marchetti, C., Marie, H., Tirozzi, B., & Migliore, M. (2012). On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons. Journal of Computational Neuroscience, 33(2), 207–225. https://doi.org/10.1007/s10827-012-0383-y
Pospischil, M., Toledo-Rodriguez, M., Monier, C., Piwkowska, Z., Bal, T., Frégnac, Y., Markram, H., & Destexhe, A. (2008). Minimal Hodgkin-Huxley type models for different classes of cortical and thalamic neurons. Biological Cybernetics, 99(4–5), 427–441. https://doi.org/10.1007/s00422-008-0263-8
Migliore, M., Hoffman, D. A., Magee, J. C., & Johnston, D. (1999). Role of an A-type K+ conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons. Journal of Computational Neuroscience, 7(1), 5–15. https://doi.org/10.1023/A:1008906225285
Sáray, S., Rössert, C. A., Appukuttan, S., Migliore, R., Vitale, P., Lupascu, C. A., Bologna, L. L., Van Geit, W., Romani, A., Davison, A. P., Muller, E., Freund, T. F., & Káli, S. (2021). HippoUnit: A software tool for the automated testing and systematic comparison of detailed models of hippocampal neurons based on electrophysiological data. PLOS Computational Biology, 17(1), e1008114. https://doi.org/10.1371/journal.pcbi.1008114
Tomko, M., Benuskova, L., & Jedlicka, P. (2021). A new reduced-morphology model for CA1 pyramidal cells and its validation and comparison with other models using HippoUnit. Scientific Reports, 11, 7615. https://doi.org/10.1038/s41598-021-87002-7
Appukuttan, S., & Davison, A. P. (2022). Reproducing and quantitatively validating a biologically-constrained point-neuron model of CA1 pyramidal cells. Frontiers in Integrative Neuroscience, 16, 1041423. https://doi.org/10.3389/fnint.2022.1041423
Bock, T., Negrean, A., & Siegelbaum, S. A. (2022). Somatic depolarization enhances hippocampal CA1 dendritic spike propagation and distal input-driven synaptic plasticity. The Journal of Neuroscience, 42(16), 3406–3425. https://doi.org/10.1523/JNEUROSCI.0780-21.2022
Pagkalos, M., Chavlis, S., & Poirazi, P. (2023). Introducing the Dendrify framework for incorporating dendrites to spiking neural networks. Nature Communications, 14, 131. https://doi.org/10.1038/s41467-022-35747-8
Marasco, A., Tribuzi, C., Lupascu, C. A., & Migliore, M. (2024). Modeling realistic synaptic inputs of CA1 hippocampal pyramidal neurons and interneurons via Adaptive Generalized Leaky Integrate-and-Fire models. Mathematical Biosciences, 372, 109192. https://doi.org/10.1016/j.mbs.2024.109192
Golomb, D., Yue, C., & Yaari, Y. (2006). Contribution of persistent Na+ current and M-type K+ current to somatic bursting in CA1 pyramidal cells: combined experimental and modeling study. Journal of Neurophysiology, 96(4), 1912–1926. https://doi.org/10.1152/jn.00205.2006
Hines, M. L., & Carnevale, N. T. (1997). The NEURON simulation environment. Neural Computation, 9(6), 1179–1209. https://doi.org/10.1162/neco.1997.9.6.1179
Hines, M. L., & Carnevale, N. T. (2001). NEURON: a tool for neuroscientists. The Neuroscientist, 7(2), 123–135. https://doi.org/10.1177/107385840100700207
Carnevale, N. T., & Hines, M. L. (2006). The NEURON Book. Cambridge University Press. https://doi.org/10.1017/CBO9780511541612
Spruston, N. (2008). Pyramidal neurons: dendritic structure and synaptic integration. Nature Reviews Neuroscience, 9(3), 206–221. https://doi.org/10.1038/nrn2286
Andreasen, M., & Lambert, J. D. C. (1995). Regenerative properties of pyramidal cell dendrites in area CA1 of the rat hippocampus. The Journal of Physiology, 483(2), 421–441. https://doi.org/10.1113/jphysiol.1995.sp020595
Gasparini, S., Migliore, M., & Magee, J. C. (2004). On the initiation and propagation of dendritic spikes in CA1 pyramidal neurons. The Journal of Neuroscience, 24(49), 11046–11056. https://doi.org/10.1523/JNEUROSCI.2520-04.2004
Poirazi, P., Brannon, T., & Mel, B. W. (2003a). Pyramidal neuron as two-layer neural network. Neuron, 37(6), 989–999. https://doi.org/10.1016/S0896-6273(03)00149-1
Poirazi, P., Brannon, T., & Mel, B. W. (2003b). Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron, 37(6), 977–987. https://doi.org/10.1016/S0896-6273(03)00148-X
Colbert, C. M., Magee, J. C., Hoffman, D. A., & Johnston, D. (1997). Slow recovery from inactivation of Na+ channels underlies the activity-dependent attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons. The Journal of Neuroscience, 17(17), 6512–6521. https://doi.org/10.1523/JNEUROSCI.17-17-06512.1997