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

• Published in: Cell reports (Cambridge) Vol. 23; no. 4; pp. 1034 - 1044
• Main Authors: Labarrera, Christina, Deitcher, Yair, Dudai, Amir, Weiner, Benjamin, Kaduri Amichai, Adi, Zylbermann, Neta, London, Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.04.2018; Elsevier
• Subjects: ADHD; apical tuft; Ca2+ spike; cortical layer 5 pyramidal neuron; dendrites; guanfacine; HCN; norepinephrine; somatosensory cortex; norepinephrine; ADHD; HCN; guanfacine; cortical layer 5 pyramidal neuron; dendrites; apical tuft; somatosensory cortex; Ca2+ spike; Ih; I(h); Ca(2+) spike
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.03.103

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. [Display omitted] •Blocking Ih increases apical tuft excitability in L5 pyramidal neurons in vivo•α2A adrenoceptor agonist reduces Ih in L5 pyramidal neurons•α2A adrenoceptor agonist increases apical tuft excitability in L5 pyramidal neurons•Modeling shows that adrenergic modulation of Ih effectively regulates tuft excitability 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.