Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo

Summary: The excitability of the apical tuft of layer 5 pyramidal neurons is thought to play a crucial role in behavioral performance and synaptic plasticity. We show that the excitability of the apical tuft is sensitive to adrenergic neuromodulation. Using two-photon dendritic Ca2+ imaging and in v...

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Main Authors: Christina Labarrera, Yair Deitcher, Amir Dudai, Benjamin Weiner, Adi Kaduri Amichai, Neta Zylbermann, Michael London
Format: Article
Language:English
Published: Elsevier 2018-04-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718304790
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author Christina Labarrera
Yair Deitcher
Amir Dudai
Benjamin Weiner
Adi Kaduri Amichai
Neta Zylbermann
Michael London
author_facet Christina Labarrera
Yair Deitcher
Amir Dudai
Benjamin Weiner
Adi Kaduri Amichai
Neta Zylbermann
Michael London
author_sort Christina Labarrera
collection DOAJ
description Summary: The excitability of the apical tuft of layer 5 pyramidal neurons is thought to play a crucial role in behavioral performance and synaptic plasticity. We show that the excitability of the apical tuft is sensitive to adrenergic neuromodulation. Using two-photon dendritic Ca2+ imaging and in vivo whole-cell and extracellular recordings in awake mice, we show that application of the α2A-adrenoceptor agonist guanfacine increases the probability of dendritic Ca2+ events in the tuft and lowers the threshold for dendritic Ca2+ spikes. We further show that these effects are likely to be mediated by the dendritic current Ih. Modulation of Ih in a realistic compartmental model controlled both the generation and magnitude of dendritic calcium spikes in the apical tuft. These findings suggest that adrenergic neuromodulation may affect cognitive processes such as sensory integration, attention, and working memory by regulating the sensitivity of layer 5 pyramidal neurons to top-down inputs. : Labarrera et al. show that noradrenergic neuromodulation can be an effective way to regulate the interaction between different input streams of information processed by an individual neuron. These findings may have important implications for our understanding of how adrenergic neuromodulation affects sensory integration, attention, and working memory. Keywords: cortical layer 5 pyramidal neuron, dendrites, norepinephrine, HCN, Ih, Ca2+ spike, apical tuft, guanfacine, ADHD, somatosensory cortex
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spelling doaj.art-8c923e7f53ae4de7888727d63bdc79c62022-12-22T00:12:14ZengElsevierCell Reports2211-12472018-04-0123410341044Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In VivoChristina Labarrera0Yair Deitcher1Amir Dudai2Benjamin Weiner3Adi Kaduri Amichai4Neta Zylbermann5Michael London6Edmond and Lily Safra Center for Brain Sciences and Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelEdmond and Lily Safra Center for Brain Sciences and Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelEdmond and Lily Safra Center for Brain Sciences and Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelEdmond and Lily Safra Center for Brain Sciences and Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelEdmond and Lily Safra Center for Brain Sciences and Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelEdmond and Lily Safra Center for Brain Sciences and Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelEdmond and Lily Safra Center for Brain Sciences and Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel; Corresponding authorSummary: The excitability of the apical tuft of layer 5 pyramidal neurons is thought to play a crucial role in behavioral performance and synaptic plasticity. We show that the excitability of the apical tuft is sensitive to adrenergic neuromodulation. Using two-photon dendritic Ca2+ imaging and in vivo whole-cell and extracellular recordings in awake mice, we show that application of the α2A-adrenoceptor agonist guanfacine increases the probability of dendritic Ca2+ events in the tuft and lowers the threshold for dendritic Ca2+ spikes. We further show that these effects are likely to be mediated by the dendritic current Ih. Modulation of Ih in a realistic compartmental model controlled both the generation and magnitude of dendritic calcium spikes in the apical tuft. These findings suggest that adrenergic neuromodulation may affect cognitive processes such as sensory integration, attention, and working memory by regulating the sensitivity of layer 5 pyramidal neurons to top-down inputs. : Labarrera et al. show that noradrenergic neuromodulation can be an effective way to regulate the interaction between different input streams of information processed by an individual neuron. These findings may have important implications for our understanding of how adrenergic neuromodulation affects sensory integration, attention, and working memory. Keywords: cortical layer 5 pyramidal neuron, dendrites, norepinephrine, HCN, Ih, Ca2+ spike, apical tuft, guanfacine, ADHD, somatosensory cortexhttp://www.sciencedirect.com/science/article/pii/S2211124718304790
spellingShingle Christina Labarrera
Yair Deitcher
Amir Dudai
Benjamin Weiner
Adi Kaduri Amichai
Neta Zylbermann
Michael London
Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo
Cell Reports
title Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo
title_full Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo
title_fullStr Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo
title_full_unstemmed Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo
title_short Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo
title_sort adrenergic modulation regulates the dendritic excitability of layer 5 pyramidal neurons in vivo
url http://www.sciencedirect.com/science/article/pii/S2211124718304790
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