[go: up one dir, main page]
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Locus coeruleus activation enhances thalamic feature selectivity via norepinephrine regulation of intrathalamic circuit dynamics

Nature Neuroscience volume 22, pages 120–133 (2019)Cite this article

Subjects

Abstract

We investigated locus coeruleus (LC) modulation of thalamic feature selectivity through reverse correlation analysis of single-unit recordings from different stages of the rat vibrissa pathway. LC activation increased feature selectivity, drastically improving thalamic information transmission. We found that this improvement was dependent on both local activation of α-adrenergic receptors and modulation of T-type calcium channels in the thalamus and was not due to LC modulation of trigeminothalamic feedforward or corticothalamic feedback inputs. Tonic spikes with LC stimulation carried three times the information as did tonic spikes without LC stimulation. Modeling confirmed norepinephrine regulation of intrathalamic circuit dynamics led to the improved information transmission. Behavioral data demonstrated that LC activation increased the perceptual performance of animals performing tactile discrimination tasks through LC–norepinephrine optimization of thalamic sensory processing. These results suggest a new subdimension within the tonic mode in which brain state can optimize thalamic sensory processing through modulation of intrathalamic circuit dynamics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: White noise reverse-correlation analysis for estimation of thalamic feature selectivity during different LC activation conditions.
Fig. 2: LC activation increased VPm feature selectivity and improved information transmission while decreasing firing rate.
Fig. 3: LC-activation-induced increase in thalamic information transmission was not due to modulation of the trigeminothalamic feedforward or corticothalamic feedback inputs.
Fig. 4: LC-activation-induced increase in thalamic information transmission was dependent on the action of alpha-adrenergic receptors in the thalamus.
Fig. 5: LC-activation modulated intrathalamic circuit dynamics.
Fig. 6: LC activation improved thalamic information transmission through modulation of T-type calcium channel activity.
Fig. 7: Modeling results indicated that NE action in both the VPm and TRN is optimal for enhancing thalamic information transmission.
Fig. 8: Photostimulation of LC improved behavioral performance in tactile discrimination tasks through LC–NE optimization of thalamic sensory processing.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Briggs, F., Mangun, G. R. & Usrey, W. M. Attention enhances synaptic efficacy and the signal-to-noise ratio in neural circuits. Nature 499, 476–480 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Poulet, J. F. A. & Petersen, C. C. H. Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. Nature 454, 881–885 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Cano, M., Bezdudnaya, T., Swadlow, H. A. & Alonso, J.-M. Brain state and contrast sensitivity in the awake visual thalamus. Nat. Neurosci. 9, 1240–1242 (2006).

    Article  CAS  PubMed  Google Scholar 

  4. Niell, C. M. & Stryker, M. P. Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65, 472–479 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Reimer, J. et al. Pupil fluctuations track fast switching of cortical states during quiet wakefulness. Neuron 84, 355–362 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. McGinley, M. J., David, S. V. & McCormick, D. A. Cortical membrane potential signature of optimal states for sensory signal detection. Neuron 87, 179–192 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vinck, M., Batista-Brito, R., Knoblich, U. & Cardin, J. A. Arousal and locomotion make distinct contributions to cortical activity patterns and visual encoding. Neuron 86, 740–754 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Scholvinck, M. L., Saleem, A. B., Benucci, A., Harris, K. D. & Carandini, M. Cortical state determines global variability and correlations in visual cortex. J. Neurosci. 35, 170–178 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sara, SusanJ. & Bouret, S. Orienting and reorienting: the locus coeruleus mediates cognition through arousal. Neuron 76, 130–141 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. Aston-Jones, G. & Cohen, J. D. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu. Rev. Neurosci. 28, 403–450 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Usher, M., Cohen, J. D., Servan-Schreiber, D., Rajkowski, J. & Aston-Jones, G. The role of locus coeruleus in the regulation of cognitive performance. Science 283, 549–554 (1999).

    Article  CAS  PubMed  Google Scholar 

  12. Devilbiss, D. M., Page, M. E. & Waterhouse, B. D. Locus ceruleus regulates sensory encoding by neurons and networks in waking animals. J. Neurosci. 26, 9860–9872 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. McGinley, M. J. et al. Waking state: rapid variations modulate neural and behavioral responses. Neuron 87, 1143–1161 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Steriade, M., McCormick, D. A. & Sejnowski, T. J. Thalamocortical oscillations in the sleeping and aroused brain. Science 262, 679–685 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Guo, Z. V. et al. Maintenance of persistent activity in a frontal thalamocortical loop. Nature 545, 181–186 (2017).

    Article  CAS  PubMed  Google Scholar 

  16. Wang, H.-P., Spencer, D., Fellous, J.-M. & Sejnowski, T. J. Synchrony of thalamocortical inputs maximizes cortical reliability. Science 328, 106–109 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang, Q., Webber, R. & Stanley, G. B. Thalamic synchrony and the adaptive gating of information flow to cortex. Nat. Neurosci. 13, 1534–1541 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wimmer, R. D. et al. Thalamic control of sensory selection in divided attention. Nature 526, 705–709 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Crick, F. Function of the thalamic reticular complex: the searchlight hypothesis. Proc. Natl Acad. Sci. USA 81, 4586–4590 (1984).

    Article  CAS  PubMed  Google Scholar 

  20. Petersen, R. S. et al. Diverse and temporally precise kinetic feature selectivity in the VPm thalamic nucleus. Neuron 60, 890–903 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Jadhav, S. P., Wolfe, J. & Feldman, D. E. Sparse temporal coding of elementary tactile features during active whisker sensation. Nat. Neurosci. 12, 792–800 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Vaingankar, V., Soto-Sanchez, C., Wang, X., Sommer, F. T. & Hirsch, J. A. Neurons in the thalamic reticular nucleus are selective for diverse and complex visual features. Front. Integr. Neurosci. 6, 118 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Liu, Y., Rodenkirch, C., Moskowitz, N., Schriver, B. & Wang, Q. Dynamic lateralization of pupil dilation evoked by locus coeruleus activation results from sympathetic, not parasympathetic, contributions. Cell Rep. 20, 3099–3112 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Mainen, Z. F. & Sejnowski, T. J. Reliability of spike timing in neocortical neurons. Science 268, 1503–1506 (1995).

    Article  CAS  PubMed  Google Scholar 

  25. Adelman, T. L., Bialek, W. & Olberg, R. M. The information content of receptive fields. Neuron 40, 823–833 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Abbott, S. B. G., Stornetta, R. L., Socolovsky, C. S., West, G. H. & Guyenet, P. G. Photostimulation of channelrhodopsin-2 expressing ventrolateral medullary neurons increases sympathetic nerve activity and blood pressure in rats. J. Physiol. 587, 5613–5631 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Crandall, S. R., Cruikshank, S. J. & Connors, B. W. A corticothalamic switch: controlling the thalamus with dynamic synapses. Neuron 86, 768–782 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Berridge, C. W. & Waterhouse, B. D. The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain. Res. Rev. 42, 33–84 (2003).

    Article  PubMed  Google Scholar 

  29. Martins, A. R. O. & Froemke, R. C. Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex. Nat. Neurosci. 18, 1483–1492 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ramcharan, E. J., Gnadt, J. W. & Sherman, S. M. Burst and tonic firing in thalamic cells of unanesthetized, behaving monkeys. Vis. Neurosci. 17, 55–62 (2000).

    Article  CAS  PubMed  Google Scholar 

  31. Reinagel, P., Godwin, D., Sherman, S. M. & Koch, C. Encoding of visual information by LGN bursts. J. Neurophysiol. 81, 2558–2569 (1999).

    Article  CAS  PubMed  Google Scholar 

  32. Moxon, K. A., Devilbiss, D. M., Chapin, J. K. & Waterhouse, B. D. Influence of norepinephrine on somatosensory neuronal responses in the rat thalamus: A combined modeling and in vivo multi-channel, multi-neuron recording study. Brain Res. 1147, 105–123 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Harris, K. D. & Thiele, A. Cortical state and attention. Nat. Rev. Neurosci. 12, 509–523 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hirata, A., Aguilar, J. & Castro-Alamancos, M. A. Noradrenergic activation amplifies bottom-up and top-down signal-to-noise ratios in sensory thalamus. J. Neurosci. 26, 4426–4436 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Joshi, S., Li, Y., Kalwani, Rishi M. & Gold, Joshua I. Relationships between pupil diameter and neuronal activity in the locus coeruleus, colliculi, and cingulate cortex. Neuron 89, 221–234 (2016).

  36. Polack, P. O., Friedman, J. & Golshani, P. Cellular mechanisms of brain state-dependent gain modulation in visual cortex. Nat. Neurosci. 16, 1331–1339 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Goard, M. & Dan, Y. Basal forebrain activation enhances cortical coding of natural scenes. Nat. Neurosci. 12, 1444–1449 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Pinto, L. et al. Fast modulation of visual perception by basal forebrain cholinergic neurons. Nat. Neurosci. 16, 1857–1863 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Fu, Y. et al. A cortical circuit for gain control by behavioral state. Cell 156, 1139–1152 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lee, A. M. et al. Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion. Neuron 83, 455–466 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sherman, S. M. Tonic and burst firing: dual modes of thalamocortical relay. Trends Neurosci. 24, 122–126 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Llinas, R. & Jahnsen, H. Electrophysiology of mammalian thalamic neurones in vitro. Nature 297, 406–408 (1982).

    Article  CAS  PubMed  Google Scholar 

  43. Fanselow, E. E., Sameshima, K., Baccala, L. A. & Nicolelis, M. A. Thalamic bursting in rats during different awake behavioral states. Proc. Natl Acad. Sci. USA 98, 15330–15335 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Swadlow, H. A. & Gusev, A. G. The impact of ‘bursting’ thalamic impulses at a neocortical synapse. Nat. Neurosci. 4, 402–408 (2001).

    Article  CAS  PubMed  Google Scholar 

  45. Halassa, M. M. et al. Selective optical drive of thalamic reticular nucleus generates thalamic bursts and cortical spindles. Nat. Neurosci. 14, 1118–1120 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Avanzini, G., de Curtis, M., Panzica, F. & Spreafico, R. Intrinsic properties of nucleus reticularis thalami neurones of the rat studied in vitro. J. Physiol. 416, 111–122 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Deleuze, C. et al. T-type calcium channels consolidate tonic action potential output of thalamic neurons to neocortex. J. Neurosci. 32, 12228–12236 (2012).

    Article  CAS  PubMed  Google Scholar 

  48. Wolfart, J., Debay, D., Le Masson, G., Destexhe, A. & Bal, T. Synaptic background activity controls spike transfer from thalamus to cortex. Nat. Neurosci. 8, 1760–1767 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Bennett, C., Arroyo, S. & Hestrin, S. Subthreshold mechanisms underlying state-dependent modulation of visual responses. Neuron 80, 350–357 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Stern, E. A., Kincaid, A. E. & Wilson, C. J. Spontaneous subthreshold membrane potential fluctuations and action potential variability of rat corticostriatal and striatal neurons in vivo. J. Neurophysiol. 77, 1697–1715 (1997).

    Article  CAS  PubMed  Google Scholar 

  51. Minnery, B. S. & Simons, D. J. Response properties of whisker-associated trigeminothalamic neurons in rat nucleus principalis. J. Neurophysiol. 89, 40–56 (2003).

    Article  PubMed  Google Scholar 

  52. Xiang, Z. et al. The discovery and characterization of ML218: a novel, centrally active T-Type calcium channel inhibitor with robust effects in STN neurons and in a rodent model of parkinson’s disease. ACS Chem. Neurosci. 2, 730–742 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Moore, J. D. et al. Hierarchy of orofacial rhythms revealed through whisking and breathing. Nature 497, 205–210 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Schwartz, O., Pillow, J. W., Rust, N. C. & Simoncelli, E. P. Spike-triggered neural characterization. J. Vis. 6, 484–507 (2006).

    Article  PubMed  Google Scholar 

  55. Lesica, N. A. et al. Dynamic encoding of natural luminance sequences by LGN bursts. PLoS Biol. 4, e209 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank J. M. Alonso for comments at various points of this work and R. L. Stornetta for sharing lentiviral vectors with us. This work was supported by the National Institutes of Health (NIH R01MH112267 to Q.W.).

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Charles Rodenkirch, Yang Liu, Brian J. Schriver & Qi Wang

Authors
  1. Charles Rodenkirch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian J. Schriver
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Q.W. and C.R. designed the project. C.R, Y.L., and Q.W. performed in vivo experiments. C.R. analyzed the data and performed modeling with Q.W.’s guidance. B.J.S. performed and analyzed behavioral experiments. Q.W. supervised the entire project. Q.W. and C.R. wrote the manuscript with input from Y.L and B.J.S.

Corresponding author

Correspondence to Qi Wang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Integrated supplementary information

Supplementary Figure 1 Experimental setup and electrophysiology of VPm neurons.

(a) Example voltage traces of evoked single-unit VPm activity from the beginning (top), ~2 hours (middle) and ~3.5 hours (bottom) of a recording. Inset: corresponding VPm spike waveforms; shaded area represents ±s.d. (n=300 spikes). (b) Measured spectrum of the WGN deflection provided by the custom modified galvomotor.

Supplementary Figure 2 LC activation increased thalamic feature selectivity and improved information transmission.

(a) Population average of peak-to-peak amplitude of significant features for VPm neurons under varying LC stimulation conditions (1.49±0.22 without LC stimulation vs 1.85±0.28 during 2 Hz LC stimulation and 2.38±0.36 during 5 Hz LC stimulation, n=41 features across 22 neurons across 15 animals, Bonferroni corrected α=0.025, p=1.3x10-6 and =2.5x10-8 respectively, Wilcoxon signed-rank test). Each circle represents a significant feature. (b) Population average of information transmission efficiency (bits/spike) for VPm neurons under varying LC stimulation conditions (0.15±0.03 bits/spike without LC stimulation vs 0.32±0.12 bits/spike during 2 Hz LC stimulation and 0.60±0.16 bits/spike during 5 Hz LC stimulation, n=41 features across 22 neurons across 15 animals, Bonferroni corrected α = 0.025, p=6.7x10-6 and =2.5x10-8 respectively, Wilcoxon signed-rank test). Each circle represents a significant feature. (c) Population average of information transmission rate (bits/second) for VPm neurons under varying LC stimulation conditions (0.97±0.17 bits/sec without LC stimulation vs 1.43±0.37 bits/sec during 2 Hz LC stimulation and 2.0±0.40 bits/sec during 5 Hz LC stimulation, n=41 features across 22 neurons across 15 animals, Bonferroni corrected α = 0.025, p=3.0x10-3 and =2.5x10-6 respectively, Wilcoxon signed-rank test). Each circle represents a significant feature. Error bars indicate ±s.e.m.

Supplementary Figure 3 Optogenetic LC stimulation improved thalamocortical information transmission.

(a) Example of recovered features for a VPm neuron under varying LC photostimulation conditions. Inset: the nonlinear tuning functions of the same neuron. (b) Population average of information transmission efficiency (bits/spike) for VPm neurons under varying LC photostimulation conditions (0.12±0.03 bits/spike without LC stimulation vs 0.26±0.06 bits/spike during 2 Hz LC stimulation and 0.50±0.12 bits/spike during 5 Hz LC stimulation, n=18 features across 10 neurons across 4 animals, Bonferroni corrected α=0.025, p=0.012 and =3.7x10-3 respectively, paired t-test). Each circle represents a significant feature. (c) Population average of information transmission rate (bits/second) for VPm neurons under varying LC photostimulation conditions (1.47±0.59 bits/sec without LC stimulation vs 2.40±0.64 bits/sec during 2 Hz LC stimulation and 3.34±0.88 bits/sec during 5 Hz LC stimulation, n=18 features across 10 neurons across 4 animals, Bonferroni corrected α=0.025, p=0.033 and =0.013 respectively, paired t-test). Each circle represents a significant feature. Error bars indicate ±s.e.m.

Supplementary Figure 4 LC activation improved feature selectivity and information transmission in the awake VPm.

(a) Example single-unit activity in awake VPm. Shaded area represents ±s.d. (n=500 spikes) (b) Example of recovered features for a VPm neuron with and without LC stimulation. Inset: corresponding nonlinear tuning functions. (c) Population average of feature modulation factor for VPm neurons with and without LC stimulation in awake rats (1 without LC stimulation vs 1.11±0.04 during 5 Hz LC stimulation, n=19 features across 13 neurons across 4 animals, α=0.05, p=0.013, paired t-test). Each circle represents a significant feature. (d) Normalized changes in information transmission efficiency (bits/spike) for VPm neurons with and without LC stimulation in awake rats (194±36% of the control during 5 Hz LC stimulation, n=19 features across 13 neurons across 4 animals, α=0.05, p=0.018, paired t-test). Each circle represents a significant feature. Error bars indicate ±s.e.m.

Supplementary Figure 5 The LC-activation-induced improvement in thalamic information transmission was not inherited from the PrV.

(a) Example single-unit PrV response to a punctate stimulation of its principal whisker, with arrow marking stimulation onset. Inset: example PrV waveform; shaded area represents ±s.d. (n=56 spikes) (b) PrV firing rate in response to WGN whisker stimulation under varying LC stimulation conditions (40±5 Hz without LC stimulation vs 39±5 Hz during 2 Hz LC stimulation and 40±5 Hz during 5 Hz LC stimulation, n=13 neurons across 8 animals, Bonferroni corrected α=0.025, p=0.28 and =0.72 respectively, paired t-test). Each circle represents a PrV neuron. (c) Population average of information transmission efficiency (bits/spike) for PrV neurons under varying LC stimulation conditions (2.06±0.65 bits/spike without LC stimulation vs 2.09±0.64 bits/spike during 2 Hz LC stimulation and 2.08±0.63 bits/spike during 5 Hz LC stimulation, n=24 features across 13 neurons across 8 animals, Bonferroni corrected α=0.025, p=0.19 and =0.89 respectively, Wilcoxon signed-rank test). Each circle represents a significant feature. Error bars indicate ±s.e.m.

Supplementary Figure 6 Inactivation of the barrel cortex by muscimol injection did not alter LC-activation-induced improvements in thalamic information transmission.

(a) Example single-unit barrel cortex response to a punctate stimulation of its principal whisker, with arrow marking stimulation onset. Inset: example barrel cortex waveform; shaded area represents ±s.d. (n=1398 spikes) (b) Example average LFP response in barrel cortex to a punctate stimulation of the cortical barrel column’s principal whisker before and after muscimol injection. Shaded area represents ±s.e.m (n=313 and =308 trials respectively). Similar results were observed in another animal. (c) Population average of information transmission efficiency (bits/spike) for VPm neurons, post cortical inactivation, under varying LC stimulation conditions (0.33±0.13 bits/spike without LC stimulation vs 0.54±0.18 bits/spike during 2 Hz LC stimulation and 0.90±0.31 bits/spike during 5 Hz LC stimulation, n=8 features across 7 neurons across 4 animals, Bonferroni corrected α=0.025, p=0.017 and =0.028 respectively, paired t-test). Each circle represents a significant feature. Error bars indicate ±s.e.m.

Supplementary Figure 7 The LC-activation-induced increase in thalamic information transmission was due to the action of NE in the thalamus.

(a) Population average of information transmission efficiency (bits/spike) for VPm neurons, prior to phentolamine injection, under varying LC stimulation conditions (0.21±0.09 bits/spike without LC stimulation vs 0.75±0.49 bits/spike during 2 Hz LC stimulation and 1.23±0.60 bits/spike during 5 Hz LC stimulation, n=10 features across 6 neurons across 4 animals, Bonferroni corrected α=0.025, p=0.002 and =0.078, respectively, paired t-test). Each circle represents a significant feature. (b) Population average of information transmission efficiency (bits/spike) for VPm neurons, post phentolamine injection, under varying LC stimulation conditions (0.33±0.12 bits/spike without LC stimulation vs 0.32±0.12 bits/spike during 2 Hz LC stimulation and 0.32±0.11 bits/spike during 5 Hz LC stimulation, n=10 features across 5 neurons across 4 animals, Bonferroni corrected α=0.025, p=0.64 and =0.76 respectively, paired t-test). Each circle represents a significant feature. (c) Population average of information transmission efficiency (bits/spike) for VPm neurons, post saline injection, under varying LC stimulation conditions (0.05±0.01 bits/spike without LC stimulation vs 0.10±0.02 bits/spike during 2 Hz LC stimulation and 0.13±0.02 bits/spike during 5 Hz LC stimulation, n=7 features across 4 neurons across 4 animals, Bonferroni corrected α=0.025, p=0.037 and =1.7x10-4 respectively, paired t-test). Each circle represents a significant feature. Error bars indicate ±s.e.m.

Supplementary Figure 8 LC activation did not significantly alter the precision of spike timing within events for VPm neurons.

VPm precision in response to WGN whisker stimulation under varying LC stimulation conditions (2.3±0.1 ms without LC stimulation vs 2.5±0.2 ms during 2 Hz LC stimulation and 2.8±0.4 ms during 5 Hz LC stimulation, n=22 neurons across 15 animals, Bonferroni corrected α=0.025, p=0.16 and =0.14, respectively, paired t-test). Each circle represents a VPm neuron.

Supplementary Figure 9 LC activation modulated intrathalamic circuit dynamics by reducing burst firing in both the TRN and VPm.

(a) Population average of percent of spikes in bursts for VPm and TRN neurons under varying LC stimulation conditions (VPm: 26±2% without LC stimulation vs 21±2% during 2 Hz LC stimulation and 14±2% during 5 Hz LC stimulation, n=22 neurons across 15 animals, Bonferroni corrected α=0.025, p=3.8x10-4 and =1.1x10-7, respectively, paired t-test; TRN: 17±3% without LC stimulation vs 10±3% during 2 Hz LC stimulation and 8±3% during 5 Hz LC stimulation, n=21 neurons across 10 animals, Bonferroni corrected α=0.025, p=0.031 and =0.007, respectively, paired t-test). (b) Example plots from the same VPm neuron showing inter-spike-intervals (ISIs) before vs after each spike in response to WGN whisker stimulation. Left: without LC stimulation. Right: with 5 Hz LC stimulation. (c) Example single-unit TRN response to a punctate stimulation of its principal whisker, with arrow marking whisker stimulation onset. Inset: example TRN waveform; shaded area represents ±s.d. (n=220 spikes) (d) Example plots from the same TRN neuron showing ISIs before and after each spike in response to WGN whisker stimulation. Left: without LC stimulation. Right: with 5 Hz LC stimulation. Error bars indicate ±s.e.m.

Supplementary Figure 10 LC-activation-induced increases in thalamic information transmission were inversely correlated with changes in bursting rate in awake rats.

A similar trend of suppression of thalamic bursts correlating with an increase in information transmission efficiency during LC activation was observed in both anesthetized and awake animals (r=-0.31, Pearson’s coefficient).

Supplementary Figure 11 NE effects on the variance of membrane potential and coefficient of variation of interspike intervals for VPm neurons.

(a) NE activation in the modelled intrathalamic circuit decreased the variance of membrane potential of VPm neurons (74±4% of the control for NE in both VPm and TRN, n=13 modelled VPm neurons, α=0.05, p=3.9x10-5, paired t-test). (b) Coefficient of variation of VPm inter-spike-intervals under varying LC stimulation conditions (1.56±0.04 without LC stimulation vs 1.57±0.10 during 2 Hz LC stimulation and 1.36±0.05 during 5 Hz LC stimulation, n=22 neurons across 15 animals, Bonferroni corrected α=0.025, p=0.90 and =4.0 x10-4 respectively, Wilcoxon signed-rank test). Each dot represents a VPm neuron. Error bars indicate ±s.e.m.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rodenkirch, C., Liu, Y., Schriver, B.J. et al. Locus coeruleus activation enhances thalamic feature selectivity via norepinephrine regulation of intrathalamic circuit dynamics. Nat Neurosci 22, 120–133 (2019). https://doi.org/10.1038/s41593-018-0283-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41593-018-0283-1

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing