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3. Human neocortical expansion involves glutamatergic neuron diversification

Author

Berg, Jim, Sorensen, Staci A., Ting, Jonathan T., Miller, Jeremy A., Chartrand, Thomas, Buchin, Anatoly, Bakken, Trygve E., Budzillo, Agata, Dee, Nick, Ding, Song-Lin, Gouwens, Nathan W., Hodge, Rebecca D., Kalmbach, Brian, Lee, Changkyu, Lee, Brian R., Alfiler, Lauren, Baker, Katherine, Barkan, Eliza, Beller, Allison, Berry, Kyla, Bertagnolli, Darren, Bickley, Kris, Bomben, Jasmine, Braun, Thomas, Brouner, Krissy, Casper, Tamara, Chong, Peter, Crichton, Kirsten, Dalley, Rachel, de Frates, Rebecca, Desta, Tsega, Lee, Samuel Dingman, D’Orazi, Florence, Dotson, Nadezhda, Egdorf, Tom, Enstrom, Rachel, Farrell, Colin, Feng, David, Fong, Olivia, Furdan, Szabina, Galakhova, Anna A., Gamlin, Clare, Gary, Amanda, Glandon, Alexandra, Goldy, Jeff, Gorham, Melissa, Goriounova, Natalia A., Gratiy, Sergey, Graybuck, Lucas, Gu, Hong, Hadley, Kristen, Hansen, Nathan, Heistek, Tim S., Henry, Alex M., Heyer, Djai B., Hill, DiJon, Hill, Chris, Hupp, Madie, Jarsky, Tim, Kebede, Sara, Keene, Lisa, Kim, Lisa, Kim, Mean-Hwan, Kroll, Matthew, Latimer, Caitlin, Levi, Boaz P., Link, Katherine E., Mallory, Matthew, Mann, Rusty, Marshall, Desiree, Maxwell, Michelle, McGraw, Medea, McMillen, Delissa, Melief, Erica, Mertens, Eline J., Mezei, Leona, Mihut, Norbert, Mok, Stephanie, Molnar, Gabor, Mukora, Alice, Ng, Lindsay, Ngo, Kiet, Nicovich, Philip R., Nyhus, Julie, Olah, Gaspar, Oldre, Aaron, Omstead, Victoria, Ozsvar, Attila, Park, Daniel, Peng, Hanchuan, Pham, Trangthanh, Pom, Christina A., Potekhina, Lydia, Rajanbabu, Ramkumar, Ransford, Shea, Reid, David, Rimorin, Christine, Ruiz, Augustin, Sandman, David, Sulc, Josef, Sunkin, Susan M., Szafer, Aaron, Szemenyei, Viktor, Thomsen, Elliot R., Tieu, Michael, Torkelson, Amy, Trinh, Jessica, Tung, Herman, Wakeman, Wayne, Waleboer, Femke, Ward, Katelyn, Wilbers, René, Williams, Grace, Yao, Zizhen, Yoon, Jae-Geun, Anastassiou, Costas, Arkhipov, Anton, Barzo, Pal, Bernard, Amy, Cobbs, Charles, de Witt Hamer, Philip C., Ellenbogen, Richard G., Esposito, Luke, Ferreira, Manuel, Gwinn, Ryder P., Hawrylycz, Michael J., Hof, Patrick R., Idema, Sander, Jones, Allan R., Keene, C. Dirk, Ko, Andrew L., Murphy, Gabe J., Ng, Lydia, Ojemann, Jeffrey G., Patel, Anoop P., Phillips, John W., Silbergeld, Daniel L., Smith, Kimberly, Tasic, Bosiljka, Yuste, Rafael, Segev, Idan, de Kock, Christiaan P. J., Mansvelder, Huibert D., Tamas, Gabor, Zeng, Hongkui, Koch, Christof, and Lein, Ed S.

Published
2021
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4. Author Correction: Human neocortical expansion involves glutamatergic neuron diversification

Author

Berg, Jim, Sorensen, Staci A., Ting, Jonathan T., Miller, Jeremy A., Chartrand, Thomas, Buchin, Anatoly, Bakken, Trygve E., Budzillo, Agata, Dee, Nick, Ding, Song-Lin, Gouwens, Nathan W., Hodge, Rebecca D., Kalmbach, Brian, Lee, Changkyu, Lee, Brian R., Alfiler, Lauren, Baker, Katherine, Barkan, Eliza, Beller, Allison, Berry, Kyla, Bertagnolli, Darren, Bickley, Kris, Bomben, Jasmine, Braun, Thomas, Brouner, Krissy, Casper, Tamara, Chong, Peter, Crichton, Kirsten, Dalley, Rachel, de Frates, Rebecca, Desta, Tsega, Lee, Samuel Dingman, D’Orazi, Florence, Dotson, Nadezhda, Egdorf, Tom, Enstrom, Rachel, Farrell, Colin, Feng, David, Fong, Olivia, Furdan, Szabina, Galakhova, Anna A., Gamlin, Clare, Gary, Amanda, Glandon, Alexandra, Goldy, Jeff, Gorham, Melissa, Goriounova, Natalia A., Gratiy, Sergey, Graybuck, Lucas, Gu, Hong, Hadley, Kristen, Hansen, Nathan, Heistek, Tim S., Henry, Alex M., Heyer, Djai B., Hill, DiJon, Hill, Chris, Hupp, Madie, Jarsky, Tim, Kebede, Sara, Keene, Lisa, Kim, Lisa, Kim, Mean-Hwan, Kroll, Matthew, Latimer, Caitlin, Levi, Boaz P., Link, Katherine E., Mallory, Matthew, Mann, Rusty, Marshall, Desiree, Maxwell, Michelle, McGraw, Medea, McMillen, Delissa, Melief, Erica, Mertens, Eline J., Mezei, Leona, Mihut, Norbert, Mok, Stephanie, Molnar, Gabor, Mukora, Alice, Ng, Lindsay, Ngo, Kiet, Nicovich, Philip R., Nyhus, Julie, Olah, Gaspar, Oldre, Aaron, Omstead, Victoria, Ozsvar, Attila, Park, Daniel, Peng, Hanchuan, Pham, Trangthanh, Pom, Christina A., Potekhina, Lydia, Rajanbabu, Ramkumar, Ransford, Shea, Reid, David, Rimorin, Christine, Ruiz, Augustin, Sandman, David, Sulc, Josef, Sunkin, Susan M., Szafer, Aaron, Szemenyei, Viktor, Thomsen, Elliot R., Tieu, Michael, Torkelson, Amy, Trinh, Jessica, Tung, Herman, Wakeman, Wayne, Waleboer, Femke, Ward, Katelyn, Wilbers, René, Williams, Grace, Yao, Zizhen, Yoon, Jae-Geun, Anastassiou, Costas, Arkhipov, Anton, Barzo, Pal, Bernard, Amy, Cobbs, Charles, de Witt Hamer, Philip C., Ellenbogen, Richard G., Esposito, Luke, Ferreira, Manuel, Gwinn, Ryder P., Hawrylycz, Michael J., Hof, Patrick R., Idema, Sander, Jones, Allan R., Keene, C. Dirk, Ko, Andrew L., Murphy, Gabe J., Ng, Lydia, Ojemann, Jeffrey G., Patel, Anoop P., Phillips, John W., Silbergeld, Daniel L., Smith, Kimberly, Tasic, Bosiljka, Yuste, Rafael, Segev, Idan, de Kock, Christiaan P. J., Mansvelder, Huibert D., Tamas, Gabor, Zeng, Hongkui, Koch, Christof, and Lein, Ed S.

Published
2022
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6. Single-neuron models linking electrophysiology, morphology, and transcriptomics across cortical cell types

Author

Nandi, Anirban, primary, Chartrand, Thomas, additional, Van Geit, Werner, additional, Buchin, Anatoly, additional, Yao, Zizhen, additional, Lee, Soo Yeun, additional, Wei, Yina, additional, Kalmbach, Brian, additional, Lee, Brian, additional, Lein, Ed, additional, Berg, Jim, additional, Sümbül, Uygar, additional, Koch, Christof, additional, Tasic, Bosiljka, additional, and Anastassiou, Costas A., additional

Published
2022
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7. Author Correction:Human neocortical expansion involves glutamatergic neuron diversification (Nature, (2021), 598, 7879, (151-158), 10.1038/s41586-021-03813-8)

Author

Berg, Jim, Sorensen, Staci A., Ting, Jonathan T., Miller, Jeremy A., Chartrand, Thomas, Buchin, Anatoly, Bakken, Trygve E., Budzillo, Agata, Dee, Nick, Ding, Song-Lin, Gouwens, Nathan W., Hodge, Rebecca D., Kalmbach, Brian, Lee, Changkyu, Lee, Brian R., Alfiler, Lauren, Baker, Katherine, Barkan, Eliza, Beller, Allison, Berry, Kyla, Bertagnolli, Darren, Bickley, Kris, Bomben, Jasmine, Braun, Thomas, Brouner, Krissy, Casper, Tamara, Chong, Peter, Crichton, Kirsten, Dalley, Rachel, de Frates, Rebecca, Desta, Tsega, Lee, Samuel Dingman, D’Orazi, Florence, Dotson, Nadezhda, Egdorf, Tom, Enstrom, Rachel, Farrell, Colin, Feng, David, Fong, Olivia, Furdan, Szabina, Galakhova, Anna A., Gamlin, Clare, Gary, Amanda, Glandon, Alexandra, Goldy, Jeff, Gorham, Melissa, Goriounova, Natalia A., Gratiy, Sergey, Graybuck, Lucas, Gu, Hong, Hadley, Kristen, Hansen, Nathan, Heistek, Tim S., Henry, Alex M., Heyer, Djai B., Hill, DiJon, Hill, Chris, Hupp, Madie, Jarsky, Tim, Kebede, Sara, Keene, Lisa, Kim, Lisa, Kim, Mean-Hwan, Kroll, Matthew, Latimer, Caitlin, Levi, Boaz P., Link, Katherine E., Mallory, Matthew, Mann, Rusty, Marshall, Desiree, Maxwell, Michelle, McGraw, Medea, McMillen, Delissa, Melief, Erica, Mertens, Eline J., Mezei, Leona, Mihut, Norbert, Mok, Stephanie, Molnar, Gabor, Mukora, Alice, Ng, Lindsay, Ngo, Kiet, Nicovich, Philip R., Nyhus, Julie, Olah, Gaspar, Oldre, Aaron, Omstead, Victoria, Ozsvar, Attila, Park, Daniel, Peng, Hanchuan, Pham, Trangthanh, Pom, Christina A., Potekhina, Lydia, Rajanbabu, Ramkumar, Ransford, Shea, Reid, David, Rimorin, Christine, Ruiz, Augustin, Sandman, David, Sulc, Josef, Sunkin, Susan M., Szafer, Aaron, Szemenyei, Viktor, Thomsen, Elliot R., Tieu, Michael, Torkelson, Amy, Trinh, Jessica, Tung, Herman, Wakeman, Wayne, Waleboer, Femke, Ward, Katelyn, Wilbers, René, Williams, Grace, Yao, Zizhen, Yoon, Jae-Geun, Anastassiou, Costas, Arkhipov, Anton, Barzo, Pal, Bernard, Amy, Cobbs, Charles, de Witt Hamer, Philip C., Ellenbogen, Richard G., Esposito, Luke, Ferreira, Manuel, Gwinn, Ryder P., Hawrylycz, Michael J., Hof, Patrick R., Idema, Sander, Jones, Allan R., Keene, C. Dirk, Ko, Andrew L., Murphy, Gabe J., Ng, Lydia, Ojemann, Jeffrey G., Patel, Anoop P., Phillips, John W., Silbergeld, Daniel L., Smith, Kimberly, Tasic, Bosiljka, Yuste, Rafael, Segev, Idan, de Kock, Christiaan P. J., Mansvelder, Huibert D., Tamas, Gabor, Zeng, Hongkui, Koch, Christof, and Lein, Ed S.

Abstract

In the version of this Article initially published, the Acknowledgements statement contained an error. Originally appearing with thanks for support given in part as follows, “R01EY023173 from The National Eye Institute, U01MH105982 from the National Institute of Mental Health and Eunice Kennedy Shriver National Institute of Child Health and Human Development, and R011EY023173 from The National Institute of Allergy and Infectious Disease,” the last number (R011EY023173) was mistakenly added and is not in fact a grant or one provided by the NIAID. The mention has been removed. The changes have been made to the online version of the Article.

Published
2022

8. Multi-modal characterization and simulation of human epileptic circuitry

Author

Buchin, Anatoly, de Frates, Rebecca, Nandi, Anirban, Mann, Rusty, Chong, Peter, Ng, Lindsay, Miller, Jeremy, Hodge, Rebecca, Kalmbach, Brian, Bose, Soumita, Rutishauser, Ueli, McConoughey, Stephen, Lein, Ed, Berg, Jim, Sorensen, Staci, Gwinn, Ryder, Koch, Christof, Ting, Jonathan, Anastassiou, Costas A., Buchin, Anatoly, de Frates, Rebecca, Nandi, Anirban, Mann, Rusty, Chong, Peter, Ng, Lindsay, Miller, Jeremy, Hodge, Rebecca, Kalmbach, Brian, Bose, Soumita, Rutishauser, Ueli, McConoughey, Stephen, Lein, Ed, Berg, Jim, Sorensen, Staci, Gwinn, Ryder, Koch, Christof, Ting, Jonathan, and Anastassiou, Costas A.

Abstract

Temporal lobe epilepsy is the fourth most common neurological disorder with about 40% of patients not responding to pharmacological treatment. Increased cellular loss in the hippocampus is linked to disease severity and pathological phenotypes such as heightened seizure propensity. While the hippocampus is the target of therapeutic interventions such as temporal lobe resection, the impact of the disease at the cellular level remains unclear in humans. Here we show that properties of hippocampal granule cells change with disease progression as measured in living, resected hippocampal tissue excised from epilepsy patients. We show that granule cells increase excitability and shorten response latency while also enlarging in cellular volume, surface area and spine density. Single-cell RNA sequencing combined with simulations ascribe the observed electrophysiological changes to gradual modification in three key ion channel conductances: BK, Cav2.2 and Kir2.1. In a bio-realistic computational network model, we show that the changes related to disease progression bring the circuit into a more excitable state. In turn, we observe that by reversing these changes in the three key conductances produces a less excitable, early disease-like state. These results provide mechanistic understanding of epilepsy in humans and will inform future therapies such as viral gene delivery to reverse the course of the disorder.

Published
2020

9. Multi-modal characterization and simulation of human epileptic circuitry

Author

Buchin, Anatoly, primary, de Frates, Rebecca, additional, Nandi, Anirban, additional, Mann, Rusty, additional, Chong, Peter, additional, Ng, Lindsay, additional, Miller, Jeremy, additional, Hodge, Rebecca, additional, Kalmbach, Brian, additional, Bose, Soumita, additional, Rutishauser, Ueli, additional, McConoughey, Stephen, additional, Lein, Ed, additional, Berg, Jim, additional, Sorensen, Staci, additional, Gwinn, Ryder, additional, Koch, Christof, additional, Ting, Jonathan, additional, and Anastassiou, Costas A., additional

Published
2020
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10. Single-neuron models linking electrophysiology, morphology and transcriptomics across cortical cell types

Author

Nandi, Anirban, primary, Chartrand, Tom, additional, Geit, Werner Van, additional, Buchin, Anatoly, additional, Yao, Zizhen, additional, Lee, Soo Yeun, additional, Wei, Yina, additional, Kalmbach, Brian, additional, Lee, Brian, additional, Lein, Ed, additional, Berg, Jim, additional, Sümbül, Uygar, additional, Koch, Christof, additional, Tasic, Bosiljka, additional, and Anastassiou, Costas A., additional

Published
2020
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11. Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

Author

Berg, Jim, primary, Sorensen, Staci A., additional, Ting, Jonathan T., additional, Miller, Jeremy A., additional, Chartrand, Thomas, additional, Buchin, Anatoly, additional, Bakken, Trygve E., additional, Budzillo, Agata, additional, Dee, Nick, additional, Ding, Song-Lin, additional, Gouwens, Nathan W., additional, Hodge, Rebecca D., additional, Kalmbach, Brian, additional, Lee, Changkyu, additional, Lee, Brian R., additional, Alfiler, Lauren, additional, Baker, Katherine, additional, Barkan, Eliza, additional, Beller, Allison, additional, Berry, Kyla, additional, Bertagnolli, Darren, additional, Bickley, Kris, additional, Bomben, Jasmine, additional, Braun, Thomas, additional, Brouner, Krissy, additional, Casper, Tamara, additional, Chong, Peter, additional, Crichton, Kirsten, additional, Dalley, Rachel, additional, de Frates, Rebecca, additional, Desta, Tsega, additional, Dingman Lee, Samuel, additional, D’Orazi, Florence, additional, Dotson, Nadezhda, additional, Egdorf, Tom, additional, Enstrom, Rachel, additional, Farrell, Colin, additional, Feng, David, additional, Fong, Olivia, additional, Furdan, Szabina, additional, Galakhova, Anna A., additional, Gamlin, Clare, additional, Gary, Amanda, additional, Glandon, Alexandra, additional, Goldy, Jeff, additional, Gorham, Melissa, additional, Goriounova, Natalia A., additional, Gratiy, Sergey, additional, Graybuck, Lucas, additional, Gu, Hong, additional, Hadley, Kristen, additional, Hansen, Nathan, additional, Heistek, Tim S., additional, Henry, Alex M., additional, Heyer, Djai B., additional, Hill, DiJon, additional, Hill, Chris, additional, Hupp, Madie, additional, Jarsky, Tim, additional, Kebede, Sara, additional, Keene, Lisa, additional, Kim, Lisa, additional, Kim, Mean-Hwan, additional, Kroll, Matthew, additional, Latimer, Caitlin, additional, Levi, Boaz P., additional, Link, Katherine E., additional, Mallory, Matthew, additional, Mann, Rusty, additional, Marshall, Desiree, additional, Maxwell, Michelle, additional, McGraw, Medea, additional, McMillen, Delissa, additional, Melief, Erica, additional, Mertens, Eline J., additional, Mezei, Leona, additional, Mihut, Norbert, additional, Mok, Stephanie, additional, Molnar, Gabor, additional, Mukora, Alice, additional, Ng, Lindsay, additional, Ngo, Kiet, additional, Nicovich, Philip R., additional, Nyhus, Julie, additional, Olah, Gaspar, additional, Oldre, Aaron, additional, Omstead, Victoria, additional, Ozsvar, Attila, additional, Park, Daniel, additional, Peng, Hanchuan, additional, Pham, Trangthanh, additional, Pom, Christina A., additional, Potekhina, Lydia, additional, Rajanbabu, Ramkumar, additional, Ransford, Shea, additional, Reid, David, additional, Rimorin, Christine, additional, Ruiz, Augustin, additional, Sandman, David, additional, Sulc, Josef, additional, Sunkin, Susan M., additional, Szafer, Aaron, additional, Szemenyei, Viktor, additional, Thomsen, Elliot R., additional, Tieu, Michael, additional, Torkelson, Amy, additional, Trinh, Jessica, additional, Tung, Herman, additional, Wakeman, Wayne, additional, Ward, Katelyn, additional, Wilbers, René, additional, Williams, Grace, additional, Yao, Zizhen, additional, Yoon, Jae-Geun, additional, Anastassiou, Costas, additional, Arkhipov, Anton, additional, Barzo, Pal, additional, Bernard, Amy, additional, Cobbs, Charles, additional, de Witt Hamer, Philip C., additional, Ellenbogen, Richard G., additional, Esposito, Luke, additional, Ferreira, Manuel, additional, Gwinn, Ryder P., additional, Hawrylycz, Michael J., additional, Hof, Patrick R., additional, Idema, Sander, additional, Jones, Allan R., additional, Keene, C.Dirk, additional, Ko, Andrew L., additional, Murphy, Gabe J., additional, Ng, Lydia, additional, Ojemann, Jeffrey G., additional, Patel, Anoop P., additional, Phillips, John W., additional, Silbergeld, Daniel L., additional, Smith, Kimberly, additional, Tasic, Bosiljka, additional, Yuste, Rafael, additional, Segev, Idan, additional, de Kock, Christiaan P.J., additional, Mansvelder, Huibert D., additional, Tamas, Gabor, additional, Zeng, Hongkui, additional, Koch, Christof, additional, and Lein, Ed S., additional

Published
2020
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12. h-channels contribute to divergent electrophysiological properties of supragranular pyramidal neurons in human versus mouse cerebral cortex

Author

Kalmbach, Brian E, Buchin, Anatoly, Long, Brian, Close, Jennie, Nandi, Anirban, Miller, Jeremy A, Bakken, Trygve E, Hodge, Rebecca D, Chong, Peter, de Frates, Rebecca, Dai, Kael, Maltzer, Zoe, Nicovich, Philip R, Keene, C Dirk, Silbergeld, Daniel L, Gwinn, Ryder P, Cobbs, Charles, Ko, Andrew L, Ojemann, Jeffrey G, Koch, Christof, Anastassiou, Costas A, Lein, Ed S, and Ting, Jonathan T

Subjects
Adult, Cerebral Cortex, Male, Potassium Channels, Pyramidal Cells, Cell Membrane, Models, Neurological, food and beverages, Mice, Transgenic, Article, Membrane Potentials, Mice, Inbred C57BL, nervous system, Species Specificity, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Animals, Humans, Female
Abstract

Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single-cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse, supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provide evidence that h-channels promote the transfer of theta frequencies from dendrite-to-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property.

Published
2018

13. h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex

Author

Kalmbach, Brian E., primary, Buchin, Anatoly, additional, Long, Brian, additional, Close, Jennie, additional, Nandi, Anirban, additional, Miller, Jeremy A., additional, Bakken, Trygve E., additional, Hodge, Rebecca D., additional, Chong, Peter, additional, de Frates, Rebecca, additional, Dai, Kael, additional, Maltzer, Zoe, additional, Nicovich, Philip R., additional, Keene, C. Dirk, additional, Silbergeld, Daniel L., additional, Gwinn, Ryder P., additional, Cobbs, Charles, additional, Ko, Andrew L., additional, Ojemann, Jeffrey G., additional, Koch, Christof, additional, Anastassiou, Costas A., additional, Lein, Ed S., additional, and Ting, Jonathan T., additional

Published
2018
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16. h-channels contribute to divergent electrophysiological properties of supragranular pyramidal neurons in human versus mouse cerebral cortex

Author

Kalmbach, Brian E, primary, Buchin, Anatoly, additional, Miller, Jeremy A, additional, Bakken, Trygve E, additional, Hodge, Rebecca D, additional, Chong, Peter, additional, de Frates, Rebecca, additional, Dai, Kael, additional, Gwinn, Ryder P., additional, Cobbs, Charles, additional, Ko, Andrew L, additional, Ojemann, Jeffrey G, additional, Silbergeld, Daniel L, additional, Koch, Christof, additional, Anastassiou, Costas A., additional, Lein, Ed, additional, and Ting, Jonathan T, additional

Published
2018
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17. h-channels Contribute to Divergent Electrophysiological Properties of Supragranular Pyramidal Neurons in Human Versus Mouse Cerebral Cortex

Author

Kalmbach, Brian E., primary, Buchin, Anatoly, additional, Miller, Jeremy A., additional, Bakken, Trygve E., additional, Hodge, Rebecca D., additional, Chong, Peter, additional, deFrates, Rebecca, additional, Dai, Kael, additional, Gwinn, Ryder P., additional, Cobbs, Charles, additional, Ko, Andrew L., additional, Ojemann, Jeffrey G., additional, Silbergeld, Daniel L., additional, Koch, Christof, additional, Anastassiou, Costas A., additional, Lein, Ed, additional, and Ting, Jonathan T., additional

Published
2018
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18. Inverse Stochastic Resonance in Cerebellar Purkinje Cells

Author

Buchin, Anatoly, Rieubland, Sarah, Häusser, Michael, Gutkin, Boris S., and Roth, Arnd

Subjects
Physiology, QH301-705.5, Materials Science, Material Properties, Models, Neurological, Action Potentials, Neurophysiology, Capacitance, Research and Analysis Methods, Membrane Potential, Rats, Sprague-Dawley, Purkinje Cells, Mathematical and Statistical Techniques, Animal Cells, Cerebellum, Medicine and Health Sciences, Animals, Biology (General), Neurons, Cerebral Cortex, Stochastic Processes, Biology and Life Sciences, Brain, Computational Biology, Cell Biology, Neuronal Dendrites, Curve Fitting, Rats, Electrophysiology, Cellular Neuroscience, Physical Sciences, Cellular Types, Anatomy, Mathematical Functions, Research Article, Neuroscience
Abstract

Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing., Author Summary How neurons generate output spikes in response to various combinations of inputs is a central issue in contemporary neuroscience. Due to their large dendritic tree and complex intrinsic properties, cerebellar Purkinje cells are an important model system to study this input-output transformation. Here we examine how noise can change the parameters of this transformation. In experiments we found that spike generation in Purkinje cells can be efficiently inhibited by noise of a particular amplitude. This effect is called inverse stochastic resonance (ISR) and has previously been described only in theoretical models of neurons. We explain the mechanism underlying ISR using a simple model matching the properties of experimentally characterized Purkinje cells. We found that ISR is present in Purkinje cells when the mean input current is near threshold for spike generation. ISR can be explained by the co-existence of resting and spiking solutions of the simple model. Changes of the input noise variance change the lifetime of these resting and spiking states, suggesting a mechanism for a tunable filter with long time constants implemented by a Purkinje cell population in the cerebellum. Finally, ISR leads to locally optimal information transfer from the input to the output of a Purkinje cell.

Published
2016
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19. 26th Annual Computational Neuroscience Meeting (CNS*2017): Part 2

Author

Rubchinsky, Leonid L., primary, Ahn, Sungwoo, additional, Klijn, Wouter, additional, Cumming, Ben, additional, Yates, Stuart, additional, Karakasis, Vasileios, additional, Peyser, Alexander, additional, Woodman, Marmaduke, additional, Diaz-Pier, Sandra, additional, Deraeve, James, additional, Vassena, Eliana, additional, Alexander, William, additional, Beeman, David, additional, Kudela, Pawel, additional, Boatman-Reich, Dana, additional, Anderson, William S., additional, Luque, Niceto R., additional, Naveros, Francisco, additional, Carrillo, Richard R., additional, Ros, Eduardo, additional, Arleo, Angelo, additional, Huth, Jacob, additional, Ichinose, Koki, additional, Park, Jihoon, additional, Kawai, Yuji, additional, Suzuki, Junichi, additional, Mori, Hiroki, additional, Asada, Minoru, additional, Oprisan, Sorinel A., additional, Dave, Austin I., additional, Babaie, Tahereh, additional, Robinson, Peter, additional, Tabas, Alejandro, additional, Andermann, Martin, additional, Rupp, André, additional, Balaguer-Ballester, Emili, additional, Lindén, Henrik, additional, Christensen, Rasmus K., additional, Nakamura, Mari, additional, Barkat, Tania R., additional, Tosi, Zach, additional, Beggs, John, additional, Lonardoni, Davide, additional, Boi, Fabio, additional, Di Marco, Stefano, additional, Maccione, Alessandro, additional, Berdondini, Luca, additional, Jędrzejewska-Szmek, Joanna, additional, Dorman, Daniel B., additional, Blackwell, Kim T., additional, Bauermeister, Christoph, additional, Keren, Hanna, additional, Braun, Jochen, additional, Dornas, João V., additional, Mavritsaki, Eirini, additional, Aldrovandi, Silvio, additional, Bridger, Emma, additional, Lim, Sukbin, additional, Brunel, Nicolas, additional, Buchin, Anatoly, additional, Kerr, Clifford Charles, additional, Chizhov, Anton, additional, Huberfeld, Gilles, additional, Miles, Richard, additional, Gutkin, Boris, additional, Spencer, Martin J., additional, Meffin, Hamish, additional, Grayden, David B., additional, Burkitt, Anthony N., additional, Davey, Catherine E., additional, Tao, Liangyu, additional, Tiruvadi, Vineet, additional, Ali, Rehman, additional, Mayberg, Helen, additional, Butera, Robert, additional, Gunay, Cengiz, additional, Lamb, Damon, additional, Calabrese, Ronald L., additional, Doloc-Mihu, Anca, additional, López-Madrona, Víctor J., additional, Matias, Fernanda S., additional, Pereda, Ernesto, additional, Mirasso, Claudio R., additional, Canals, Santiago, additional, Geminiani, Alice, additional, Pedrocchi, Alessandra, additional, D’Angelo, Egidio, additional, Casellato, Claudia, additional, Chauhan, Ankur, additional, Soman, Karthik, additional, Srinivasa Chakravarthy, V., additional, Muddapu, Vignayanandam R., additional, Chuang, Chao-Chun, additional, Chen, Nan-yow, additional, Bayati, Mehdi, additional, Melchior, Jan, additional, Wiskott, Laurenz, additional, Azizi, Amir Hossein, additional, Diba, Kamran, additional, Cheng, Sen, additional, Smirnova, Elena Y., additional, Yakimova, Elena G., additional, Chizhov, Anton V., additional, Chen, Nan-Yow, additional, Shih, Chi-Tin, additional, Florescu, Dorian, additional, Coca, Daniel, additional, Courtiol, Julie, additional, Jirsa, Viktor K., additional, Covolan, Roberto J. M., additional, Teleńczuk, Bartosz, additional, Kempter, Richard, additional, Curio, Gabriel, additional, Destexhe, Alain, additional, Parker, Jessica, additional, Klishko, Alexander N., additional, Prilutsky, Boris I., additional, Cymbalyuk, Gennady, additional, Franke, Felix, additional, Hierlemann, Andreas, additional, da Silveira, Rava Azeredo, additional, Casali, Stefano, additional, Masoli, Stefano, additional, Rizza, Martina, additional, Rizza, Martina Francesca, additional, Sun, Yinming, additional, Wong, Willy, additional, Farzan, Faranak, additional, Blumberger, Daniel M., additional, Daskalakis, Zafiris J., additional, Popovych, Svitlana, additional, Viswanathan, Shivakumar, additional, Rosjat, Nils, additional, Grefkes, Christian, additional, Daun, Silvia, additional, Gentiletti, Damiano, additional, Suffczynski, Piotr, additional, Gnatkovski, Vadym, additional, De Curtis, Marco, additional, Lee, Hyeonsu, additional, Paik, Se-Bum, additional, Choi, Woochul, additional, Jang, Jaeson, additional, Park, Youngjin, additional, Song, Jun Ho, additional, Song, Min, additional, Pallarés, Vicente, additional, Gilson, Matthieu, additional, Kühn, Simone, additional, Insabato, Andrea, additional, Deco, Gustavo, additional, Glomb, Katharina, additional, Ponce-Alvarez, Adrián, additional, Ritter, Petra, additional, Campo, Adria Tauste, additional, Thiele, Alexander, additional, Deeba, Farah, additional, Robinson, P. A., additional, van Albada, Sacha J., additional, Rowley, Andrew, additional, Hopkins, Michael, additional, Schmidt, Maximilian, additional, Stokes, Alan B., additional, Lester, David R., additional, Furber, Steve, additional, Diesmann, Markus, additional, Barri, Alessandro, additional, Wiechert, Martin T., additional, DiGregorio, David A., additional, Dimitrov, Alexander G., additional, Vich, Catalina, additional, Berg, Rune W., additional, Guillamon, Antoni, additional, Ditlevsen, Susanne, additional, Cazé, Romain D., additional, Girard, Benoît, additional, Doncieux, Stéphane, additional, Doyon, Nicolas, additional, Boahen, Frank, additional, Desrosiers, Patrick, additional, Laurence, Edward, additional, Dubé, Louis J., additional, Eleonora, Russo, additional, Durstewitz, Daniel, additional, Schmidt, Dominik, additional, Mäki-Marttunen, Tuomo, additional, Krull, Florian, additional, Bettella, Francesco, additional, Metzner, Christoph, additional, Devor, Anna, additional, Djurovic, Srdjan, additional, Dale, Anders M., additional, Andreassen, Ole A., additional, Einevoll, Gaute T., additional, Næss, Solveig, additional, Ness, Torbjørn V., additional, Halnes, Geir, additional, Halgren, Eric, additional, Pettersen, Klas H., additional, Sætra, Marte J., additional, Hagen, Espen, additional, Schiffer, Alina, additional, Grzymisch, Axel, additional, Persike, Malte, additional, Ernst, Udo, additional, Harnack, Daniel, additional, Ernst, Udo A., additional, Tomen, Nergis, additional, Zucca, Stefano, additional, Pasquale, Valentina, additional, Pica, Giuseppe, additional, Molano-Mazón, Manuel, additional, Chiappalone, Michela, additional, Panzeri, Stefano, additional, Fellin, Tommaso, additional, Oie, Kelvin S., additional, Boothe, David L., additional, Crone, Joshua C., additional, Yu, Alfred B., additional, Felton, Melvin A., additional, Zulfiqar, Isma, additional, Moerel, Michelle, additional, De Weerd, Peter, additional, Formisano, Elia, additional, Oie, Kelvin, additional, Franaszczuk, Piotr, additional, Diggelmann, Roland, additional, Fiscella, Michele, additional, Guarino, Domenico, additional, Antolík, Jan, additional, Davison, Andrew P., additional, Frègnac, Yves, additional, Etienne, Benjamin Xavier, additional, Frohlich, Flavio, additional, Lefebvre, Jérémie, additional, Marcos, Encarni, additional, Mattia, Maurizio, additional, Genovesio, Aldo, additional, Fedorov, Leonid A., additional, Dijkstra, Tjeerd M.H., additional, Sting, Louisa, additional, Hock, Howard, additional, Giese, Martin A., additional, Buhry, Laure, additional, Langlet, Clément, additional, Giovannini, Francesco, additional, Verbist, Christophe, additional, Salvadé, Stefano, additional, Giugliano, Michele, additional, Henderson, James A., additional, Wernecke, Hendrik, additional, Sándor, Bulcsú, additional, Gros, Claudius, additional, Voges, Nicole, additional, Dabrovska, Paulina, additional, Riehle, Alexa, additional, Brochier, Thomas, additional, Grün, Sonja, additional, Gu, Yifan, additional, Gong, Pulin, additional, Dumont, Grégory, additional, Novikov, Nikita A., additional, Gutkin, Boris S., additional, Tewatia, Parul, additional, Eriksson, Olivia, additional, Kramer, Andrei, additional, Santos, Joao, additional, Jauhiainen, Alexandra, additional, Kotaleski, Jeanette H., additional, Belić, Jovana J., additional, Kumar, Arvind, additional, Kotaleski, Jeanette Hellgren, additional, Shimono, Masanori, additional, Hatano, Naomichi, additional, Ahmad, Subutai, additional, Cui, Yuwei, additional, Hawkins, Jeff, additional, Senk, Johanna, additional, Korvasová, Karolína, additional, Tetzlaff, Tom, additional, Helias, Moritz, additional, Kühn, Tobias, additional, Denker, Michael, additional, Mana, PierGianLuca, additional, Dahmen, David, additional, Schuecker, Jannis, additional, Goedeke, Sven, additional, Keup, Christian, additional, Heuer, Katja, additional, Bakker, Rembrandt, additional, Tiesinga, Paul, additional, Toro, Roberto, additional, Qin, Wei, additional, Hadjinicolaou, Alex, additional, Ibbotson, Michael R., additional, Kameneva, Tatiana, additional, Lytton, William W., additional, Mulugeta, Lealem, additional, Drach, Andrew, additional, Myers, Jerry G., additional, Horner, Marc, additional, Vadigepalli, Rajanikanth, additional, Morrison, Tina, additional, Walton, Marlei, additional, Steele, Martin, additional, Anthony Hunt, C., additional, Tam, Nicoladie, additional, Amaducci, Rodrigo, additional, Muñiz, Carlos, additional, Reyes-Sánchez, Manuel, additional, Rodríguez, Francisco B., additional, Varona, Pablo, additional, Cronin, Joseph T., additional, Hennig, Matthias H., additional, Iavarone, Elisabetta, additional, Yi, Jane, additional, Shi, Ying, additional, Zandt, Bas-Jan, additional, Van Geit, Werner, additional, Rössert, Christian, additional, Markram, Henry, additional, Hill, Sean, additional, O’Reilly, Christian, additional, Perin, Rodrigo, additional, Lu, Huanxiang, additional, Bryson, Alexander, additional, Hadrava, Michal, additional, Hlinka, Jaroslav, additional, Hosaka, Ryosuke, additional, Olenik, Mark, additional, Houghton, Conor, additional, Iannella, Nicolangelo, additional, Launey, Thomas, additional, Kotsakidis, Rebecca, additional, Soriano, Jaymar, additional, Kubo, Takatomi, additional, Inoue, Takao, additional, Kida, Hiroyuki, additional, Yamakawa, Toshitaka, additional, Suzuki, Michiyasu, additional, Ikeda, Kazushi, additional, Abbasi, Samira, additional, Hudson, Amber E., additional, Heck, Detlef H., additional, Jaeger, Dieter, additional, Lee, Joel, additional, Janušonis, Skirmantas, additional, Saggio, Maria Luisa, additional, Spiegler, Andreas, additional, Stacey, William C., additional, Bernard, Christophe, additional, Lillo, Davide, additional, Petkoski, Spase, additional, Drakesmith, Mark, additional, Jones, Derek K., additional, Zadeh, Ali Sadegh, additional, Kambhampati, Chandra, additional, Karbowski, Jan, additional, Kaya, Zeynep Gokcen, additional, Lakretz, Yair, additional, Treves, Alessandro, additional, Li, Lily W., additional, Lizier, Joseph, additional, Kerr, Cliff C., additional, Masquelier, Timothée, additional, Kheradpisheh, Saeed Reza, additional, Kim, Hojeong, additional, Kim, Chang Sub, additional, Marakshina, Julia A., additional, Vartanov, Alexander V., additional, Neklyudova, Anastasia A., additional, Kozlovskiy, Stanislav A., additional, Kiselnikov, Andrey A., additional, Taniguchi, Kanako, additional, Kitano, Katsunori, additional, Schmitt, Oliver, additional, Lessmann, Felix, additional, Schwanke, Sebastian, additional, Eipert, Peter, additional, Meinhardt, Jennifer, additional, Beier, Julia, additional, Kadir, Kanar, additional, Karnitzki, Adrian, additional, Sellner, Linda, additional, Klünker, Ann-Christin, additional, Kuch, Lena, additional, Ruß, Frauke, additional, Jenssen, Jörg, additional, Wree, Andreas, additional, Sanz-Leon, Paula, additional, Knock, Stuart A., additional, Chien, Shih-Cheng, additional, Maess, Burkhard, additional, Knösche, Thomas R., additional, Cohen, Charles C., additional, Popovic, Marko A., additional, Klooster, Jan, additional, Kole, Maarten H.P., additional, Roberts, Erik A., additional, Kopell, Nancy J., additional, Kepple, Daniel, additional, Giaffar, Hamza, additional, Rinberg, Dima, additional, Koulakov, Alex, additional, Forlim, Caroline Garcia, additional, Klock, Leonie, additional, Bächle, Johanna, additional, Stoll, Laura, additional, Giemsa, Patrick, additional, Fuchs, Marie, additional, Schoofs, Nikola, additional, Montag, Christiane, additional, Gallinat, Jürgen, additional, Lee, Ray X., additional, Stephens, Greg J., additional, Kuhn, Bernd, additional, Tauffer, Luiz, additional, Isope, Philippe, additional, Inoue, Katsuma, additional, Ohmura, Yoshiyuki, additional, Yonekura, Shogo, additional, Kuniyoshi, Yasuo, additional, Jang, Hyun Jae, additional, Kwag, Jeehyun, additional, de Kamps, Marc, additional, Lai, Yi Ming, additional, dos Santos, Filipa, additional, Lam, K. P., additional, Andras, Peter, additional, Imperatore, Julia, additional, Helms, Jessica, additional, Tompa, Tamas, additional, Lavin, Antonieta, additional, Inkpen, Felicity H., additional, Ashby, Michael C., additional, Lepora, Nathan F., additional, Shifman, Aaron R., additional, Lewis, John E., additional, Zhang, Zhong, additional, Feng, Yeqian, additional, Tetzlaff, Christian, additional, Kulvicius, Tomas, additional, Li, Yinyun, additional, Pena, Rodrigo F. O., additional, Bernardi, Davide, additional, Roque, Antonio C., additional, Lindner, Benjamin, additional, Vellmer, Sebastian, additional, Saudargiene, Ausra, additional, Maninen, Tiina, additional, Havela, Riikka, additional, Linne, Marja-Leena, additional, Powanwe, Arthur, additional, Longtin, Andre, additional, Garrido, Jesús A., additional, Graham, Joe W., additional, Dura-Bernal, Salvador, additional, Angulo, Sergio L., additional, Neymotin, Samuel A., additional, and Antic, Srdjan D., additional

Published
2017
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20. Modélisation de la cellule et des phénomènes de réseaux dans le système nerveux : dynamique des ions au cours des oscillations d'épilepsie et résonance stochastique inverse

Author

Buchin, Anatoly, Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole normale supérieure - ENS PARIS, Boris Gutkin, and Boris Chizhov

Subjects
Épilepsie du lobe temporal, Intracellular chloride, Inverse stochastic resonance, [SCCO.NEUR]Cognitive science/Neuroscience, Chlorure intracellulaire, Cervelet, Systèmes dynamiques, Cellules de Purkinje, Bimodality, KCC2 cotransporteur, Résonance inverse stochastique, Bruit synaptique, Purkinje cells, Inversion de GABA, Cerebellum, Dynamical systems, [SCCO.PSYC]Cognitive science/Psychology, KCC2 cotransporter, GABA reversal, Potassium extracellulaire, Temporal lobe epilepsy, Extracellular potassium, Bimodalité
Abstract

In this thesis we used dynamical systems methods and numericalsimulations to study the mechanisms of epileptic oscillations associated with ionconcentration changes and cerebellar Purkinje cell bimodal behavior. The general issue in this work is the interplay between single neuron intrinsicproperties and synaptic input structure controlling the neuronal excitability. In the first part of this thesis we focused on the role of the cellular intrinsicproperties, their control over the cellular excitability and their response to thesynaptic inputs. Specifically we asked the question how the cellular changes ininhibitory synaptic function might lead to the pathological neural activity. We developed a model of seizure initiation in temporal lobe epilepsy. Specifically we focused on the role of KCC2 cotransporter that is responsible for maintaining the baseline extracellular potassium and intracellular chloride levels in neurons. Recent experimental data has shown that this cotransporter is absent in the significant group of pyramidal cells in epileptic patients suggesting its epileptogenic role. We found that addition of the critical amount of KCC2-deficient pyramidal cells to the realistic subiculum network can switch the neural activity from normal to epileptic oscillations qualitatively reproducing the activity recorded in human epileptogenic brain slices. In the second part of this thesis we studied how synaptic noise might control the Purkinje cell excitability. We investigated the effect of spike inhibition caused by noise current injection, so-called inverse stochastic resonance (ISR). This effect has been previously found in single neuron models while we provided its first experimental evidence. We found that Purkinje cells in brain slices could be efficiently inhibited by current noise injections. This effect is well reproduced by the phenomenological model fitted for different cells. Using methods of information theory we showed that ISR supports an efficient information transmission of single Purkinje cells suggesting its role for cerebellar computations.; Dans cette thèse nous avons utilisé des méthodes de systèmes dynamiques et des simulations numériques pour étudier les mécanismes d'oscillations d'épilepsie associés à des concentrations d’ions dynamiques et au comportement bimodal des cellules Purkinje du cervelet. Le propos général de ce travail est l'interaction entre les propriétés intrinsèques des neurones simple et la structure d'entrée synaptique contrôlant l'excitabilité neuronale. Dans la première partie de la thèse nous avons développé un modèle de transition de crise épileptique dans le lobe temporal du cerveau. Plus précisément nous nous sommes concentrés sur le rôle du cotransporteur KCC2, qui est responsable de la maintenance du potassium extracellulaire et du chlorure intracellulaire dans les neurones. Des données expérimentales récentes ont montré que cette molécule est absente dans un groupe significatif de cellules pyramidales dans le tissue neuronal de patients épileptiques suggérant son rôle épileptogène. Nous avons trouvé que l'addition d’une quantité critique de cellules pyramidale KCC2 déficient au réseau de subiculum, avec une connectivité réaliste, peut provoquer la génération d’oscillations pathologiques, similaire aux oscillations enregistrées dans des tranches de cerveau épileptogène humaines. Dans la seconde partie de la thèse, nous avons étudié le rôle du bruit synaptique dans les cellules de Purkinje. Nous avons étudié l'effet de l'inhibition de la génération du potentiel d’action provoquée par injection de courant de bruit, un phénomène connu comme résonance stochastique inverse (RSI). Cet effet a déjà été trouvé dans des modèles neuronaux, et nous avons fournis sa première validation expérimentale. Nous avons trouvé que les cellules de Purkinje dans des tranches de cerveau peuvent être efficacement inhibées par des injectionsde bruit de courant. Cet effet est bien reproduit par le modèle phénoménologique adapté pour différentes cellules. En utilisant des méthodes de la théorie de l'information, nous avons montré que RSI prend en charge une transmission efficace de l'information des cellules de Purkinje simples suggérant son rôle pour les calculs du cervelet.

Published
2015

21. Modeling of single cell and network phenomena of the nervous system : ion dynamics during epileptic oscillations and inverse stochastic resonance

Author

Buchin, Anatoly, Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole normale supérieure - ENS PARIS, Boris Gutkin, Boris Chizhov, STAR, ABES, École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)

Subjects
Épilepsie du lobe temporal, Intracellular chloride, Inverse stochastic resonance, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Chlorure intracellulaire, Cervelet, Systèmes dynamiques, Cellules de Purkinje, Bimodality, KCC2 cotransporteur, Résonance inverse stochastique, Bruit synaptique, Purkinje cells, Inversion de GABA, Cerebellum, Dynamical systems, [SCCO.PSYC]Cognitive science/Psychology, [SCCO.PSYC] Cognitive science/Psychology, KCC2 cotransporter, GABA reversal, Potassium extracellulaire, Temporal lobe epilepsy, Extracellular potassium, Bimodalité
Abstract

In this thesis we used dynamical systems methods and numericalsimulations to study the mechanisms of epileptic oscillations associated with ionconcentration changes and cerebellar Purkinje cell bimodal behavior. The general issue in this work is the interplay between single neuron intrinsicproperties and synaptic input structure controlling the neuronal excitability. In the first part of this thesis we focused on the role of the cellular intrinsicproperties, their control over the cellular excitability and their response to thesynaptic inputs. Specifically we asked the question how the cellular changes ininhibitory synaptic function might lead to the pathological neural activity. We developed a model of seizure initiation in temporal lobe epilepsy. Specifically we focused on the role of KCC2 cotransporter that is responsible for maintaining the baseline extracellular potassium and intracellular chloride levels in neurons. Recent experimental data has shown that this cotransporter is absent in the significant group of pyramidal cells in epileptic patients suggesting its epileptogenic role. We found that addition of the critical amount of KCC2-deficient pyramidal cells to the realistic subiculum network can switch the neural activity from normal to epileptic oscillations qualitatively reproducing the activity recorded in human epileptogenic brain slices. In the second part of this thesis we studied how synaptic noise might control the Purkinje cell excitability. We investigated the effect of spike inhibition caused by noise current injection, so-called inverse stochastic resonance (ISR). This effect has been previously found in single neuron models while we provided its first experimental evidence. We found that Purkinje cells in brain slices could be efficiently inhibited by current noise injections. This effect is well reproduced by the phenomenological model fitted for different cells. Using methods of information theory we showed that ISR supports an efficient information transmission of single Purkinje cells suggesting its role for cerebellar computations., Dans cette thèse nous avons utilisé des méthodes de systèmes dynamiques et des simulations numériques pour étudier les mécanismes d'oscillations d'épilepsie associés à des concentrations d’ions dynamiques et au comportement bimodal des cellules Purkinje du cervelet. Le propos général de ce travail est l'interaction entre les propriétés intrinsèques des neurones simple et la structure d'entrée synaptique contrôlant l'excitabilité neuronale. Dans la première partie de la thèse nous avons développé un modèle de transition de crise épileptique dans le lobe temporal du cerveau. Plus précisément nous nous sommes concentrés sur le rôle du cotransporteur KCC2, qui est responsable de la maintenance du potassium extracellulaire et du chlorure intracellulaire dans les neurones. Des données expérimentales récentes ont montré que cette molécule est absente dans un groupe significatif de cellules pyramidales dans le tissue neuronal de patients épileptiques suggérant son rôle épileptogène. Nous avons trouvé que l'addition d’une quantité critique de cellules pyramidale KCC2 déficient au réseau de subiculum, avec une connectivité réaliste, peut provoquer la génération d’oscillations pathologiques, similaire aux oscillations enregistrées dans des tranches de cerveau épileptogène humaines. Dans la seconde partie de la thèse, nous avons étudié le rôle du bruit synaptique dans les cellules de Purkinje. Nous avons étudié l'effet de l'inhibition de la génération du potentiel d’action provoquée par injection de courant de bruit, un phénomène connu comme résonance stochastique inverse (RSI). Cet effet a déjà été trouvé dans des modèles neuronaux, et nous avons fournis sa première validation expérimentale. Nous avons trouvé que les cellules de Purkinje dans des tranches de cerveau peuvent être efficacement inhibées par des injectionsde bruit de courant. Cet effet est bien reproduit par le modèle phénoménologique adapté pour différentes cellules. En utilisant des méthodes de la théorie de l'information, nous avons montré que RSI prend en charge une transmission efficace de l'information des cellules de Purkinje simples suggérant son rôle pour les calculs du cervelet.

Published
2015

24. Associations between in vitro , in vivo and in silico cell classes in mouse primary visual cortex.

Author

Wei Y, Nandi A, Jia X, Siegle JH, Denman D, Lee SY, Buchin A, Geit WV, Mosher CP, Olsen S, and Anastassiou CA

Abstract

The brain consists of many cell classes yet in vivo electrophysiology recordings are typically unable to identify and monitor their activity in the behaving animal. Here, we employed a systematic approach to link cellular, multi-modal in vitro properties from experiments with in vivo recorded units via computational modeling and optotagging experiments. We found two one-channel and six multi-channel clusters in mouse visual cortex with distinct in vivo properties in terms of activity, cortical depth, and behavior. We used biophysical models to map the two one- and the six multi-channel clusters to specific in vitro classes with unique morphology, excitability and conductance properties that explain their distinct extracellular signatures and functional characteristics. These concepts were tested in ground-truth optotagging experiments with two inhibitory classes unveiling distinct in vivo properties. This multi-modal approach presents a powerful way to separate in vivo clusters and infer their cellular properties from first principles.

Published
2023
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