Publications

all Publications

2024

Wu, Y., Temple, B.A., Sevilla, N., Zhang, J., Zhu, H., Zolotavin, P., Jin, Y., Duarte, D., Sanders, E., Azim, E., Nimmerjahn, A., Pfaff, S.L., Luan, L., Xie, C. Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior. (2024) Cell Reports. 43(5):114199. DOI: 10.1016/j.celrep.2024.114199

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Upadhyay, A., Gradwell, M.A., Vajtay, T.J., Conner, J., Sanyal, A.A., Azadegan, C., Patel, K.R., Thackray, J.K., Bohic, M., Imai, F., Ogundare, S.O., Yoshida, Y., Abdus-Saboor, I., Azim, E., Abraira, V.E. The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States. (2024) bioRxiv. DOI: 10.1101/2024.02.20.581208

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Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. Two main drivers of peripheral tactile information, low-threshold mechanoreceptors (LTMRs) and postsynaptic dorsal column neurons (PSDCs), terminate in the brainstem dorsal column nuclei (DCN). Activity within the DRG, spinal cord, and DCN have all been implicated in mediating allodynia, yet the DCN remains understudied at the cellular, circuit, and functional levels compared to the other two. Here, we show that the gracile nucleus (Gr) of the DCN mediates tactile sensitivity for low-threshold stimuli and contributes to mechanical allodynia during neuropathic pain in mice. We found that the Gr contains local inhibitory interneurons in addition to thalamus-projecting neurons, which are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations resulted in bidirectional changes to tactile sensitivity, but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, silencing Gr projection neurons or activating Gr inhibitory neurons was able to reduce tactile hypersensitivity, and enhancing inhibition was able to ameliorate paw withdrawal signatures of neuropathic pain, like shaking. Collectively, these results suggest that the Gr plays a specific role in mediating hypersensitivity to low-threshold, innocuous mechanical stimuli during neuropathic pain, and that Gr activity contributes to affective, pain-associated phenotypes of mechanical allodynia. Therefore, these brainstem circuits work in tandem with traditional spinal circuits underlying allodynia, resulting in enhanced signaling of tactile stimuli in the brain during neuropathic pain.

Wirthlin, M.E., Schmid, T.A., Elie, J.E., Zhang, X., Kowalczyk, A., Redlich, R., Shvareva, V.A., Rakuljic, A., Ji, M.B., Bhat, N.S., Kaplow, I.M., Schäffer, D.E., Lawler, A.J., Wang, A.Z., Phan, B.N., Annaldasula, S., Brown, A.R., Lu, T., Lim, B.K., Azim, E., ., Clark, N.L., Meyer, W.K., Pond, S.L.K., Chikina, M., Yartsev, M.M., Pfenning, A.R., Andrews, G., Armstrong, J.C., Bianchi, M., Birren, B.W., Bredemeyer, K.R., Breit, A.M., Christmas, M.J., Clawson, H., Damas, J., Di Palma, F., Diekhans, M., Dong, M.X., Eizirik, E., Fan, K., Fanter, C., Foley, N.M., Forsberg-Nilsson, K., Garcia, C.J., Gatesy, J., Gazal, S., Genereux, D.P., Goodman, L., Grimshaw, J., Halsey, M.K., Harris, A.J., Hickey, G., Hiller, M., Hindle, A.G., Hubley, R.M., Hughes, G.M., Johnson, J., Juan, D., Kaplow, I.M., Karlsson, E.K., Keough, K.C., Kirilenko, B., Koepfli, K.P., Korstian, J.M., Kowalczyk, A., Kozyrev, S.V., Lawler, A.J., Lawless, C., Lehmann, T., Levesque, D.L., Lewin, H.A., Li, X., Lind, A., Lindblad-Toh, K., Mackay-Smith, A., Marinescu, V.D., Marques-Bonet, T., Mason, V.C., Meadows, J.R.S., Meyer, W.K., Moore, J.E., Moreira, L.R., Moreno-Santillan, D.D., Morrill, K.M., Muntané, G., Murphy, W.J., Navarro, A., Nweeia, M., Ortmann, S., Osmanski, A., Paten, B., Paulat, N.S., Pfenning, A.R., Phan, B.N., Pollard, K.S., Pratt, H.E., Ray, D.A., Reilly, S.K., Rosen, J.R., Ruf, I., Ryan, L., Ryder, O.A., Sabeti, P.C., Schäffer, D.E., Serres, A., Shapiro, B., Smit, A.F.A., Springer, M., Srinivasan, C., Steiner, C., Storer, J.M., Sullivan, K.A.M., Sullivan, P.F., Sundström, E., Supple, M.A., Swofford, R., Talbot, J.E., Teeling, E., Turner-Maier, J., Valenzuela, A., Wagner, F., Wallerman, O., Wang, C., Wang, J., Weng, Z., Wilder, A.P., Wirthlin, M.E., Xue, J.R., Zhang, X. Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements. (2024) Science.:eabn3263 DOI: 10.1126/science.abn3263

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2023

Chung, B., Zia, M., Thomas, K.A., Michaels, J.A., Jacob, A., Pack, A., Williams, M.J., Nagapudi, K., Teng, L.H., Arrambide, E., Ouellette, L., Oey, N., Gibbs, R., Anschutz, P., Lu, J., Wu, Y., Kashefi, M., Oya, T., Kersten, R., Mosberger, A.C., O’Connell, S., Wang, R., Marques, H., Mendes, A.R., Lenschow, C., Kondakath, G., Kim, J.J., Olson, W., Quinn, K.N., Perkins, P., Gatto, G., Thanawalla, A., Coltman, S., Kim, T., Smith, T., Binder-Markey, B., Zaback, M., Thompson, C.K., Giszter, S., Person, A., Goulding, M., Azim, E., Thakor, N., O’Connor, D., Trimmer, B., Lima, S.Q., Carey, M.R., Pandarinath, C., Costa, R.M., Pruszynski, J.A., Bakir, M., Sober, S.J. Myomatrix arrays for high-definition muscle recording. (2023) Elife. 12. DOI: 10.7554/eLife.88551

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Butler, D.J., Keim, A.P., Ray, S., Azim, E. Large-scale capture of hidden fluorescent labels for training generalizable markerless motion capture models. (2023) Nature Communications. 14(1):5866. DOI: 10.1038/s41467-023-41565-3

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2021

Low, A.Y.T., Goldstein, N., Gaunt, J.R., Huang, K.P., Zainolabidin, N., Yip, A.K.K., Carty, J.R.E., Choi, J.Y., Miller, A.M., Ho, H.S.T., Lenherr, C., Baltar, N., Azim, E., Sessions, O.M., Ch’ng, T.H., Bruce, A.S., Martin, L.E., Halko, M.A., Brady, R.O., Holsen, L.M., Alhadeff, A.L., Chen, A.I., Betley, J.N. Reverse-translational identification of a cerebellar satiation network. (2021) Nature. DOI: 10.1038/s41586-021-04143-5

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Conner, J.M., Bohannon, A., Igarashi, M., Taniguchi, J., Baltar, N., Azim, E. Modulation of tactile feedback for the execution of dexterous movement. (2021) Science. 374(6565):316-323. DOI: 10.1126/science.abh1123

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Karashchuk, P., Rupp, K.L., Dickinson, E.S., Walling-Bell, S., Sanders, E., Azim, E., Brunton, B.W., Tuthill, J.C. Anipose: A toolkit for robust markerless 3D pose estimation. (2021) Cell Reports. 36(13):109730. DOI: 10.1016/j.celrep.2021.109730

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2020

Thanawalla, A.R., Chen, A.I., Azim, E. The cerebellar nuclei and dexterous limb movements. (2020) Neuroscience. DOI: 10.1016/j.neuroscience.2020.06.046

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2019

Azim, E., Seki, K. Gain control in the sensorimotor system. (2019) Current Opinion in Physiology. 8:177-187. DOI: 10.1016/j.cophys.2019.03.005

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2018

Tuthill, J.C., Azim, E. Proprioception. (2018) Current Biology. 28(5):R194-R203. DOI: 10.1016/j.cub.2018.01.064

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2016

Kishi, N., MacDonald, J.L., Ye, J., Molyneaux, B.J., Azim, E., Macklis, J.D. Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice. (2016) Nature Communications. 7:10520. DOI: 10.1038/ncomms10520

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2015

Azim, E., Alstermark, B. Skilled forelimb movements and internal copy motor circuits. (2015) Current Opinion in Neurobiology. 33:16-24. DOI: 10.1016/j.conb.2014.12.009

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Jiang, J., Azim, E., Ekerot, C.F., Alstermark, B. Direct and indirect spino-cerebellar pathways: shared ideas but different functions in motor control. (2015) Frontiers in Computational Neuroscience. 9:75. DOI: 10.3389/fncom.2015.00075

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2014

Azim, E. Neuroscience. Shortcuts and checkpoints on the road to skilled movement. (2014) Science. 346(6209):554-5. DOI: 10.1126/science.1260778

Fink, A.J., Croce, K.R., Huang, Z.J., Abbott, L.F., Jessell, T.M., Azim, E. Presynaptic inhibition of spinal sensory feedback ensures smooth movement. (2014) Nature. 509(7498):43-8. DOI: 10.1038/nature13276

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Azim, E., Jiang, J., Alstermark, B., Jessell, T.M. Skilled reaching relies on a V2a propriospinal internal copy circuit. (2014) Nature. 508(7496):357-63. DOI: 10.1038/nature13021

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Azim, E., Fink, A.J., Jessell, T.M. Internal and External Feedback Circuits for Skilled Forelimb Movement. (2014) Cold Spring Harbor Symposia on Quantitative Biology. 79:81-92. DOI: 10.1101/sqb.2014.79.024786

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2013

Miri, A., Azim, E., Jessell, T.M. Edging toward entelechy in motor control. (2013) Neuron. 80(3):827-34. DOI: 10.1016/j.neuron.2013.10.049

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Cederquist, G.Y., Azim, E., Shnider, S.J., Padmanabhan, H., Macklis, J.D. Lmo4 establishes rostral motor cortex projection neuron subtype diversity. (2013) Journal of Neuroscience. 33(15):6321-32. DOI: 10.1523/JNEUROSCI.5140-12.2013

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Azim, E. Specification of Cortical Projection Neurons: Transcriptional Mechanisms (2013) Patterning and Cell Type Specification in the Developing CNS and PNS Comprehensive Developmental Neuroscience. DOI: https://doi.org/10.1016/B978-0-12-397265-1.00098-8

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2009

Azim, E., Jabaudon, D., Fame, R.M., Macklis, J.D. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development. (2009) Nature Neuroscience. 12(10):1238-47. DOI: 10.1038/nn.2387

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Azim, E., Shnider, S.J., Cederquist, G.Y., Sohur, U.S., Macklis, J.D. Lmo4 and Clim1 progressively delineate cortical projection neuron subtypes during development. (2009) Cereb. Cortex. 19 Suppl 1:i62-9. DOI: 10.1093/cercor/bhp030

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2008

Lai, T., Jabaudon, D., Molyneaux, B.J., Azim, E., Arlotta, P., Menezes, J.R., Macklis, J.D. SOX5 controls the sequential generation of distinct corticofugal neuron subtypes. (2008) Neuron. 57(2):232-47. DOI: 10.1016/j.neuron.2007.12.023

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2005

Azim, E., Mobbs, D., Jo, B., Menon, V., Reiss, A.L. Sex differences in brain activation elicited by humor. (2005) Proceedings of the National Academy of Sciences of the United States of America. 102(45):16496-501. DOI: 10.1073/pnas.0408456102

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Mobbs, D., Hagan, C.C., Azim, E., Menon, V., Reiss, A.L. Personality predicts activity in reward and emotional regions associated with humor. (2005) Proceedings of the National Academy of Sciences of the United States of America. 102(45):16502-6. DOI: 10.1073/pnas.0408457102

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2003

Mobbs, D., Greicius, M.D., Abddel-Azim, E., Menon, V., Reiss, A.L. Humor modulates the mesolimbic reward centers. (2003) Neuron. 40(5):1041-8. DOI: 10.1016/s0896-6273(03)00751-7

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