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

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

doi:10.1016/j.celrep.2018.03.103

Cited by 69 publications

(79 citation statements)

References 78 publications

(119 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, we found that local dendrites in the barrel cortex 95 responded to auditory stimulation, and the probability of these events increases monotonically with the activity levels of NE axons. Our results are consistent with the hypothesis that NE can tune the excitability and sensitivity of dendrites to long range input projections (Phillips et al 2016(Phillips et al , 2018Labarrera et al 2018) .…”

supporting

confidence: 92%

“…Our study is in line with the proposal that large Ca 2+ events in the dendrites are tuned by NE and that the sensitivity of the dendrites is modulated by NE (Phillips et al 2016(Phillips et al , 2018Labarrera et al 2018). Future experiments aimed at establishing this hypothesis 360 will ideally include recordings from both NE signals and local dendritic activity in awake, behaving animals while they engage in a perceptual task.…”

supporting

confidence: 86%

“…However, there is little mechanistic understanding of how NE changes contribute to these effects on perception at the circuit and cellular level. One candidate mechanism is the contribution of NE to synergistic integration of information from different sources through its effect on dendritic excitability (Barth et al 2008;Phillips et al 2016Phillips et al , 2018Labarrera et al 2018).…”

Section: Ne Signals and Dendritic Computation In Perceptual Sensitivitymentioning

confidence: 99%

“…Comparison of the mean evoked Ca 2+ response to the CSs in all mice.250Nonlinear relationship between auditory evoked LC axonal and local dendritic responses in barrel cortexHaving established evoked responses of NE axons activity in the barrel cortex, we next aimed to explore the relationship between noradrenergic axon transient responses and the local circuit activity. Previously it has been suggested that the excitability of 255 dendrites located in the upper layers of the cortex is subject to neuromodulation(Barth et al 2008;Dembrow et al 2010;Labarrera et al 2018;Williams and Fletcher 2019).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Nonlinear relationship between multimodal adrenergic responses and local dendritic activity in primary sensory cortices

Deitcher

Leibner

Kutzkel

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

The axonal projections of the adrenergic system to the neocortex, originating from the locus coeruleus (LC), form a dense network. These axons release the neuromodulator norepinephrine (NE) which is involved in many cognitive functions such as attention, arousal, and working memory. Using two-photon Ca 2+ imaging of NE axons in the 15 cortex of awake mice, we investigated what drives their phasic activity. We discovered that NE axons in the primary somatosensory cortex responded robustly and reliably to somatosensory stimulation. Surprisingly, the same axons also responded to stimuli of other modalities (auditory and visual). Similar responses to all three modalities were observed in the primary visual cortex as well. These results indicate that phasic 20 responses of NE axons to sensory stimuli provide a robust multimodal signal. However, despite the robustness, we also noticed consistent variations in the data. For example, responses to whisker stimulations were larger than to auditory and visual stimulations in both the barrel and the visual cortices. To test whether the variations in NE axonal responses can carry behaviorally meaningful information, we trained mice in an 25 associative auditory fear conditioning paradigm. We found that following conditioning the response of NE axons increased only for CS+, namely the signal undergoes experience-dependent plasticity and is specific to meaningful sounds. To test if variations in NE axonal responses can differentially affect the cortical microcircuit, we used dual-color two-photon Ca 2+ imaging and studied the relationship between the 30 activity of NE axons and local dendrites. We found dendritic Ca 2+ signals in barrel cortex in response to auditory stimuli, but these responses were variable and unreliable. Strikingly, the probability of such dendritic signals increased nonlinearly with the Ca 2+ signals of NE axons. Our results demonstrate that the phasic activity of the noradrenergic neurons may serve as a robust multimodal and plastic signal in sensory 35 cortices. Furthermore, the variations in the NE axonal activity carry behaviorally meaningful signals and can predict the probability of local dendritic Ca 2+ events. 2 Keywords 40Norepinephrine, dendritic computation, sensory cortices, locus coeruleus, cortical microcircuit, axonal two-photon imaging

show abstract

supporting

confidence: 92%

supporting

confidence: 86%

Section: Ne Signals and Dendritic Computation In Perceptual Sensitivitymentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Nonlinear relationship between multimodal adrenergic responses and local dendritic activity in primary sensory cortices

Deitcher

Leibner

Kutzkel

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…5E, F ), although considerable variability between 28-40Hz was observed for the peak frequencies. We have previously shown that alterations in I h , modulatable via norepinephrine and other neurohumoral factors 73 , would alter resonance properties and activation in a model PT5B cell 98 . Here, we examined whether such alteration in just one cell type would ramify throughout the network to produce widespread dynamical changes.…”

Section: Oscillations and Cross-frequency Couplingmentioning

confidence: 99%

Multiscale dynamics and information flow in a data-driven model of the primary motor cortex microcircuit

Durá-Bernal

Neymotin

Suter

et al. 2017

Preprint

View full text Add to dashboard Cite

We developed a biologically detailed multiscale model of mouse primary motor cortex (M1) microcircuits, incorporating data from several recent experimental studies. The model simulates at scale a cylindrical volume with a diameter of 300 m and cortical depth 1350 m of M1. It includes over 10,000 cells distributed across cortical layers based on measured cell densities, with close to 30 million synaptic connections. Neuron models were optimized to reproduce electrophysiological properties of major classes of M1 neurons. Layer 5 corticospinal and corticostriatal neuron morphologies with 700+ compartments reproduced cell 3D reconstructions, and their ionic channel distributions were optimized within experimental constraints to reproduce in vitro recordings. The network was driven by the main long-range inputs to M1: posterior nucleus (PO) and ventrolateral (VL) thalamus PO, primary and secondary somatosensory cortices (S1, S2), contralateral M1, secondary motor cortex (M2), and orbital cortex (OC). The network local and long-range connections depended on pre-and post-synaptic cell class and cortical depth. Data was based on optogenetic circuit mapping studies which determined that connection strengths vary within layer as a function of the neuron's cortical depth. The synaptic input distribution across cell dendritic trees -likely to subserve important neural coding functions -was also mapped using optogenetic methods and incorporated into the model. We employed the model to study the effect on M1 of increased activity from each of the long-range inputs, and of different levels of H-current in pyramidal tract-projecting (PT) corticospinal neurons. Microcircuit dynamics and information flow were quantified using firing rates, oscillations, and information transfer measures (Spectral Granger causality). We evaluated the response to short pulses and long time-varying activity arising from the different long-range inputs. We also studied the interaction between two simultaneous long-range inputs. Simulation results support the hypothesis that M1 operates along a continuum of modes characterized by the degree of activation of intratelencephalic (IT), corticothalamic (CT) and PT neurons. The particular subset of M1 neurons targeted by different long-range inputs and the level of H-current in PT neurons regulated the different modes. Downregulation of H-current facilitated synaptic integration of inputs and increased PT output activity. Therefore, VL, cM1 and M2 inputs with downregulated H-current promoted an PT-predominant mode; whereas PO, S11 . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/201707 doi: bioRxiv preprint first posted online Oct. 11, 2017; and S2 inputs with upregulated H-current favored an IT-predominant mode, but a mixed mode where upper layer IT cells in turn activated PT cells if H-c...

show abstract

Frequency-specific modulation of oscillatory activity in the rat auditory cortex by vagus nerve stimulation

Kumagai,

Shiramatsu,

Matsumura

et al. 2023

Brain Stimulation

View full text Add to dashboard Cite

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

Cited by 69 publications

References 78 publications

Nonlinear relationship between multimodal adrenergic responses and local dendritic activity in primary sensory cortices

Nonlinear relationship between multimodal adrenergic responses and local dendritic activity in primary sensory cortices

Multiscale dynamics and information flow in a data-driven model of the primary motor cortex microcircuit

Frequency-specific modulation of oscillatory activity in the rat auditory cortex by vagus nerve stimulation

Contact Info

Product

Resources

About