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

Christina Labarrera, Yair Deitcher, Amir Dudai, Benjamin Weiner, Adi Kaduri Amichai, Neta Zylbermann, Michael London*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)1034-1044
Number of pages11
JournalCell Reports
Volume23
Issue number4
DOIs
StatePublished - 24 Apr 2018

Bibliographical note

Funding Information:
This research was supported by a grant from the Israeli Science Foundation ( 845/12 ), the Einstein Foundation , the National Institute for Psychobiology , and the Gatsby Charitable Foundation . C.L. was supported by a fellowship of the Edmond and Lily Safra Center for Brain Science . M.L. is a Sachs Family Lecturer in Brain Science. We thank N. Yayon for assistance with imaging analysis; A. Libster, Y. Nir, Y. Yarom, and I. Segev for fruitful discussions; and I. Goshen, A. Citri, I. Duguid, S. Goodman, and M. Häusser for comments on the manuscript.

Publisher Copyright:
© 2018

Keywords

  • ADHD
  • Ca spike
  • HCN
  • I
  • apical tuft
  • cortical layer 5 pyramidal neuron
  • dendrites
  • guanfacine
  • norepinephrine
  • somatosensory cortex

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