Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex
Open accessAbstract
The cerebral cortex is plastic and represents the world according to the significance of sensory stimuli. However, cortical networks are embodied in complex circuits, including neuromodulatory systems such as the noradrenergic locus coeruleus, providing information about internal state and behavioral relevance. Although norepinephrine is important for cortical plasticity, it is unknown how modulatory neurons themselves respond to changes of sensory input. We examined how locus coeruleus neurons are modified by experience and the consequences of locus coeruleus plasticity for cortical representations and sensory perception. We made whole-cell recordings from rat locus coeruleus and primary auditory cortex (A1), pairing sounds with locus coeruleus activation. Although initially unresponsive, locus coeruleus neurons developed and maintained auditory responses afterwards. Locus coeruleus plasticity induced changes in A1 responses lasting at least hours and improved auditory perception for days to weeks. Our results demonstrate that locus coeruleus is highly plastic, leading to substantial changes in regulation of brain state by norepinephrine.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Aberrant phasic NA may change the signal-to-noise ratio of cortical responses, broaden sensory tuning functions, and improve discrimination behaviour.
“Aberrant phasic NA (c.f precision on prediction errors4,6) may alter the signal-to-noise ratio of cortical responses 41,42, broaden the tuning functions of sensory responses and, subsequently improve discrimination behaviour43.”
From Adults with autism overestimate the volatility of the sensory environment (2017) · cites this paper as [43]
The Results section (‘Locus coeruleus pairing improves auditory perception’; page not available) reports that auditory-cortical tuning initially broadened and discrimination later improved above baseline. But it says performance initially worsened during the broadening phase and improved after tuning width recovered; it does not show that broadening itself improved discrimination. The source studies locus coeruleus pairing, not aberrant phasic noradrenaline. (LLM, conf=0.86)
Experimental — accuracy not yet measuredStimulation of the locus coeruleus can markedly enhance auditory cortical responses and increase learning induced plasticity.
“Stimulation of the locus coeruleus can markedly enhance auditory cortical responses and increase learning induced plasticity (Martins and Froemke, 2015).”
From Waking state: rapid variations modulate neural and behavioral responses (2015) · cites this paper as Martins and Froemke, 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A neural substrate of prediction and reward
Schultz, W., Dayan, P., & Montague, P. R. (1997) · Science · doi:10.1126/science.275.5306.1593 · Cited by 9,388 · see citing works
Aston-Jones, G., & Cohen, J. D. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135709 · Cited by 4,472 · see citing works
Synaptic Activity and the Construction of Cortical Circuits
Katz, L. C., & Shatz, C. J. (1996) · Science · doi:10.1126/science.274.5290.1133 · Cited by 3,048 · see citing works
CORTICAL PLASTICITY: From Synapses to Maps
Buonomano, D. V., & Merzenich, M. M. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.149 · Cited by 2,083 · see citing works
The locus coeruleus and noradrenergic modulation of cognition
Sara, S. J. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2573 · Cited by 1,848 · see citing works
Uncertainty, Neuromodulation, and Attention
Yu, A. J., & Dayan, P. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.026 · Cited by 1,774 · see citing works
The principal features and mechanisms of dopamine modulation in the prefrontal cortex
Seamans, J. K., & Yang, C. R. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.05.006 · Cited by 1,592 · see citing works
Hensch, T. K. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144327 · Cited by 1,300 · see citing works
Molecular mechanisms of fear learning and memory
Johansen, J. P., Cain, C. K., Ostroff, L. E., & LeDoux, J. E. (2011) · Cell · doi:10.1016/j.cell.2011.10.009 · Cited by 1,012 · see citing works
Tuning arousal with optogenetic modulation of locus coeruleus neurons
Carter, M. E., Yizhar, O., Chikahisa, S., Nguyen, H., Adamantidis, A., Nishino, S., Deisseroth, K., & de Lecea, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2682 · Cited by 993 · see citing works
Modulation of visual cortical plasticity by acetylcholine and noradrenaline
Bear, M. F., & Singer, W. (1986) · Nature · doi:10.1038/320172a0 · Cited by 858 · see citing works
Rapid task-related plasticity of spectrotemporal receptive fields in primary auditory cortex
Fritz, J. B., Shamma, S., Elhilali, M., & Klein, D. (2003) · Nature Neuroscience · doi:10.1038/nn1141 · Cited by 825 · see citing works
Gunaydin, L. A., Yizhar, O., Berndt, A., Sohal, V. S., Deisseroth, K., & Hegemann, P. (2010) · Nature Neuroscience · doi:10.1038/nn.2495 · Cited by 757 · see citing works
Oxytocin enables maternal behaviour by balancing cortical inhibition
Marlin, B. J., Mitre, M., D’amour, J. A., Chao, M. V., & Froemke, R. C. (2015) · Nature · doi:10.1038/nature14402 · Cited by 744 · see citing works
Self-citationThe role of locus coeruleus in the regulation of cognitive performance
Usher, M., Cohen, J. D., Servan-Schreiber, D., Rajkowski, J., & Aston-Jones, G. (1999) · Science · doi:10.1126/science.283.5401.549 · Cited by 715 · see citing works
Locus coeruleus neurons in monkey are selectively activated by attended cues in a vigilance task
Aston-Jones, G., Rajkowski, J., Kubiak, P., & Alexinsky, T. (1994) · The Journal of Neuroscience · doi:10.1523/jneurosci.14-07-04467.1994 · Cited by 637 · see citing works
A synaptic memory trace for cortical receptive field plasticity
Froemke, R. C., Merzenich, M. M., & Schreiner, C. E. (2007) · Nature · doi:10.1038/nature06289 · Cited by 600 · see citing works
Self-citationMap Plasticity in Somatosensory Cortex
Feldman, D. E., & Brecht, M. (2005) · Science · doi:10.1126/science.1115807 · Cited by 587 · see citing works
Cortical remodelling induced by activity of ventral tegmental dopamine neurons
Bao, S., Chan, V. T., & Merzenich, M. M. (2001) · Nature · doi:10.1038/35083586 · Cited by 569 · see citing works
Neuromodulatory transmitter systems in the cortex and their role in cortical plasticity
Gu, Q. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00026-x · Cited by 518 · see citing works
Emotion Enhances Learning via Norepinephrine Regulation of AMPA-Receptor Trafficking
Hu, H., Real, E., Takamiya, K., Kang, M.-G., Ledoux, J., Huganir, R. L., & Malinow, R. (2007) · Cell · doi:10.1016/j.cell.2007.09.017 · Cited by 496 · see citing works
Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis.
Bakin, J. S., & Weinberger, N. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.11219 · Cited by 478 · see citing works
Plasticity of Cortical Excitatory-Inhibitory Balance
Froemke, R. C. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-034002 · Cited by 458 · see citing works
Self-citationThe effects of neural gain on attention and learning
Eldar, E., Cohen, J. D., & Niv, Y. (2013) · Nature Neuroscience · doi:10.1038/nn.3428 · Cited by 402 · see citing works
Critical-Period Plasticity in the Visual Cortex
Levelt, C. N., & Hübener, M. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113813 · Cited by 402 · see citing works
Effects and Mechanisms of Wakefulness on Local Cortical Networks
Constantinople, C. M., & Bruno, R. M. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.040 · Cited by 387 · see citing works
Noradrenergic modulation of arousal
Berridge, C. W. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.10.013 · Cited by 368 · see citing works
Corticostriatal neurons in auditory cortex drive decisions during auditory discrimination
Znamenskiy, P., & Zador, A. M. (2013) · Nature · doi:10.1038/nature12077 · Cited by 339 · see citing works
Sara, S. J., & Segal, M. (1991) · Progress in brain research · doi:10.1016/s0079-6123(08)63835-2 · Cited by 223 · see citing works
Long-term modification of cortical synapses improves sensory perception
Froemke, R. C., Carcea, I., Barker, A. J., Yuan, K., Seybold, B., Martins, A. R. O., Zaika, N., Bernstein, H. L., Wachs, M. A., Levis, P. A., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3274 · Cited by 212 · see citing works
Self-citationLearning-induced plasticity in animal and human auditory cortex
Ohl, F. W., & Scheich, H. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.07.002 · Cited by 196 · see citing works
A neuronal analogue of state-dependent learning
Shulz, D. E., Sosnik, R., Ego‐Stengel, V., Haidarliu, S., & Ahissar, E. (2000) · Nature · doi:10.1038/35000586 · Cited by 153 · see citing works
Perceptual learning and adult cortical plasticity.
Gilbert, C. D., Li, W., & Piech, V. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.171488 · Cited by 151 · see citing works
Distinct Tonic and Phasic Anticipatory Activity in Lateral Habenula and Dopamine Neurons
Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010) · Neuron · doi:10.1016/j.neuron.2010.06.016 · Cited by 146 · see citing works
Devilbiss, D. M., & Waterhouse, B. D. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00445.2010 · Cited by 139 · see citing works
FROM BIOPHYSICS TO MODELS OF NETWORK FUNCTION
Marder, E. E. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.25 · Cited by 135 · see citing works
Spatiotemporal specificity in cholinergic control of neocortical function
Muñoz, W., & Rudy, B. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.02.015 · Cited by 122 · see citing works
Bush, D. E. A., Caparosa, E. M., Gekker, A., & LeDoux, J. E. (2010) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2010.00154 · Cited by 117 · see citing works
A Behavioral Framework to Guide Research on Central Auditory Development and Plasticity
Sanes, D. H., & Woolley, S. M. N. (2011) · Neuron · doi:10.1016/j.neuron.2011.12.005 · Cited by 105 · see citing works
Edeline, J., Manunta, Y., & Hennevin, E. (2010) · Hearing Research · doi:10.1016/j.heares.2010.08.005 · Cited by 96 · see citing works
Representational gain in cortical area underlies increase of memory strength
Bieszczad, K. M., & Weinberger, N. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000159107 · Cited by 90 · see citing works
Shumake, J., Ilango, A., Scheich, H., Wetzel, W., & Ohl, F. W. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3604-09.2010 · Cited by 82 · see citing works
Chun, S., Bayazitov, I. T., Blundon, J. A., & Zakharenko, S. S. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4500-12.2013 · Cited by 75 · see citing works
Kuo, S. P., & Trussell, L. O. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.039 · Cited by 57 · see citing works
In vivo patch‐clamp recording from locus coeruleus neurones in the rat brainstem
Sugiyama, D., Hur, S. W., Pickering, A. E., Kase, D., Kim, S. J., Kawamata, M., Imoto, K., & Furue, H. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.226407 · Cited by 42 · see citing works
Disney, A. A., & Reynolds, J. H. (2014) · Journal of Comparative Neurology · doi:10.1002/cne.23456 · Cited by 40 · see citing works
Spectrotemporal dynamics of auditory cortical synaptic receptive field plasticity
Froemke, R. C., & Martins, A. R. O. (2011) · Hearing Research · doi:10.1016/j.heares.2011.03.005 · Cited by 39 · see citing works
Self-citationChanging the responses of cortical neurons from sub- to suprathreshold using single spikes in vivo
Pawlak, V., Greenberg, D. S., Sprekeler, H., Gerstner, W., & Kerr, J. N. D. (2013) · eLife · doi:10.7554/elife.00012 · Cited by 37 · see citing works
Tonic effects of the dopaminergic ventral midbrain on the auditory cortex of awake macaque monkeys
Huang, Y., Mylius, J., Scheich, H., & Brosch, M. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0950-2 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [37]Aston-Jones G Rajkowski J Kubiak P Alexinsky T Locus coeruleus neurons in monkey are selectively activated by attended cues in a vigilance task J Neurosci 14 4467 4480 1994 8027789 PMC6577022
Cited by
Sorted by citations
Waking state: rapid variations modulate neural and behavioral responses
McGinley, M. J., Vinck, M., Reimer, J., Batista-Brito, R., Zagha, E., Cadwell, C. R., Tolias, A. S., Cardin, J. A., & McCormick, D. A. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.012 · Cited by 801 · see citing works
“Stimulation of the locus coeruleus can markedly enhance auditory cortical responses and increase learning induced plasticity (Martins and Froemke, 2015).”
Pupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex
Reimer, J., McGinley, M. J., Liu, Y., Rodenkirch, C., Wang, Q., McCormick, D. A., & Tolias, A. S. (2016) · Nature Communications · doi:10.1038/ncomms13289 · Cited by 926 · see citing works
Predictive Processing: A Canonical Cortical Computation
Keller, G. B., & Mrsic-Flogel, T. D. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.003 · Cited by 836 · see citing works
Locus coeruleus: a new look at the blue spot
Poe, G. R., Foote, S., Eschenko, O., Johansen, J. P., Bouret, S., Aston-Jones, G., Harley, C. W., Manahan-Vaughan, D., Weinshenker, D., Valentino, R., et al. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0360-9 · Cited by 720 · see citing works
Adults with autism overestimate the volatility of the sensory environment
Lawson, R. P., Mathys, C., & Rees, G. (2017) · Nature Neuroscience · doi:10.1038/nn.4615 · Cited by 470 · see citing works
Kaufman, A. M., Geiller, T., & Losonczy, A. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.029 · Cited by 193 · see citing works
Motor primitives in space and time via targeted gain modulation in cortical networks
Stroud, J. P., Porter, M. A., Hennequin, G., & Vogels, T. P. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0276-0 · Cited by 119 · see citing works
- Authors
- Martins, A. R. O., & Froemke, R. C.
- Affiliations
- Centro de Neurociências e Biologia Celular (PT)
- New York University (US)
- Corresponding author
- Froemke, Robert C
- ORCID
- Froemke, Robert C
- Venue
- Nature Neuroscience
- Published
- 2015-08-24
- Volume
- 18
- Issue
- 10
- Pages
- 1483-1492
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4583810
- OpenAlex
- W2342247067
- Cited by
- 233
- References
- 49
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 26 · 2023: 36 · 2022: 27 · 2021: 18 · 2020: 21 · 2019: 25 · 2018: 27 · 2017: 12 · 2016: 13 · 2015: 3
- FWCI
- 11.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Deafness and Other Communication Disorders (K99DC009635, DC009635, R00DC009635, DC012557, R01DC012557)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroscience and Music Perception
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- locus coeruleus, primary auditory cortex, norepinephrine, synaptic plasticity, auditory perception, neuromodulation
- MeSH terms
- Animals, Auditory Cortex, Female, Locus Coeruleus, Neuronal Plasticity, Rats, Sprague-Dawley, Patch-Clamp Techniques, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
