Reaching for the stars, not the spout - The role of the superior colliculus in goal-oriented forelimb movements
Reaching for the stars, not the spout - The role of the superior colliculus in goal-oriented forelimb movements
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Chaterji S, Belliappa P.H , Sathyamurthy A. The superior colliculus directs goal-oriented forelimb movements, 2024, Cell Reports
Chaterji S, Belliappa P.H , Sathyamurthy A. The superior colliculus directs goal-oriented forelimb movements, 2024, Cell Reports
https://pubmed.ncbi.nlm.nih.gov/39723891/
https://pubmed.ncbi.nlm.nih.gov/39723891/
Intraspinal delivery of AAVs (from our lab)
Intraspinal delivery of AAVs (from our lab)
Chaterji S, Barik A, Sathyamurthy A. Intraspinal injection of adeno-associated viruses into the adult mouse spinal cord. STAR Protocols. 2021 Sep 1;2(3):100786
Chaterji S, Barik A, Sathyamurthy A. Intraspinal injection of adeno-associated viruses into the adult mouse spinal cord. STAR Protocols. 2021 Sep 1;2(3):100786
https://pubmed.ncbi.nlm.nih.gov/34505088/
https://pubmed.ncbi.nlm.nih.gov/34505088/
Cells, molecules, and circuits underlying sensorimotor control (findings from studies that Dr Sathyamurthy conducted in her post-doctoral and doctoral labs)
Cells, molecules, and circuits underlying sensorimotor control (findings from studies that Dr Sathyamurthy conducted in her post-doctoral and doctoral labs)
The following studies were geared towards identifying the cells, molecules, and circuits underlying sensorimotor control. Specifically, what are the genes important for cerebellar develoment? How does the cerebellum interact with the spinal cord to bring about movement? What are the cells and molecules that make up the spinal cord? And finally, how does the spinal cord communicate with the brain to regulate the perception of pain?
The following studies were geared towards identifying the cells, molecules, and circuits underlying sensorimotor control. Specifically, what are the genes important for cerebellar develoment? How does the cerebellum interact with the spinal cord to bring about movement? What are the cells and molecules that make up the spinal cord? And finally, how does the spinal cord communicate with the brain to regulate the perception of pain?
Sathyamurthy A, Barik A, Dobrott CI, Matson KJE, Stoica S, Pursley R, Chesler AT, Levine AJ. Cerebellospinal neurons regulate motor performance and motor learning. Cell Reports. 2020 May12;31(6):107595
Sathyamurthy A, Barik A, Dobrott CI, Matson KJE, Stoica S, Pursley R, Chesler AT, Levine AJ. Cerebellospinal neurons regulate motor performance and motor learning. Cell Reports. 2020 May12;31(6):107595
How does the cerebellum exert its effect on the spinal cord, which is the final integrative centre for transforming motor commands into muscle contractions? Most contemporary and classic studies of motor control have posited that the cerebellum influences the activity of spinal neurons only through indirect, poly-synaptic relays in the brain. In this study, Sathyamurthy et al. challenge this idea and report that a small group of deep cerebelar neurons directly target the spinal cord. Using cutting edge genetic techniques, they unravel the organizational logic of this pathway, identify its spinal targets, and demonstrate for the first time a role for distinct groups of cerebellospinal neurons in different aspects of movement.
Sathyamurthy A*, Johnson KR*, Matson KJE, Dobrott CI, Li L, Ryba AR, Bergmann TB, Kelly MC, Kelley MW, Levine AJ. Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior. Cell Rep. 2018 Feb; 22(8):2216-2225. (* authors contributed equally).
Sathyamurthy A*, Johnson KR*, Matson KJE, Dobrott CI, Li L, Ryba AR, Bergmann TB, Kelly MC, Kelley MW, Levine AJ. Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior. Cell Rep. 2018 Feb; 22(8):2216-2225. (* authors contributed equally).
What cell types make up the spinal cord? Here, Sathyamurthy, Johnson et al. used massively parallel single nucleus RNA sequencing (snRNA-seq) to create an atlas of cells and molecules of the adult mouse lumbar spinal cord. First, they identified and molecularly characterized 43 neuronal populations and found that neurons readily cluster into groups based on neurotransmitter identity and position along the dorsoventral axis, and that unlike dorsal neurons, transcriptomes of ventral neurons show overlapping gene expression patterns, suggesting that these could have a continuum of phenotypes. Second, they leveraged the snRNA-seq approach to provide unbiased identification of neuronal populations that were active following a sensory and a motor behavior, using a transcriptional signature of neuronal activity.
Sathyamurthy A, Yin DM, Barik A, Shen C, Bean JC, Figueiredo D, She JX, Xiong WC, Mei L. ERBB3- mediated regulation of Bergmann glia proliferation in cerebellar lamination. Development. 2015 Feb; 142(3):522-32.
Sathyamurthy A, Yin DM, Barik A, Shen C, Bean JC, Figueiredo D, She JX, Xiong WC, Mei L. ERBB3- mediated regulation of Bergmann glia proliferation in cerebellar lamination. Development. 2015 Feb; 142(3):522-32.
Cortical lamination is crucial for the assembly of cerebellar circuitry. In the developing cerebellum, Bergmann glial cells provide a scaffold for the directed migration of granule neurons from the external granule layer to their final destinations in the internal granule layer of the cerebellum. However, the molecular mechanisms underlying Bergmann glial development are not well understood. Here, Sathyamurthy et al. show that ERBB3 is crucial for the proliferation of Bergmann glia and loss of Erbb3 in these cells leads to a dearth of glial scaffold for granule neuron migration, ultimately impairing cerebellar lamination. Overall, these observations identify a crucial role for ERBB3 (whose role were previously though to be limited to myelination) in cerebellar lamination and reveal a novel mechanism that regulates Bergmann glial development.
Cells, molecules, and circuits underlying sensorimotor control (studies that Dr Sathyamurthy contributed to in her post-doctoral and doctoral labs)
Cells, molecules, and circuits underlying sensorimotor control (studies that Dr Sathyamurthy contributed to in her post-doctoral and doctoral labs)
Matson KJE, Russ DE, Kathe C, Hua I, Maric D, Ding Y, Krynitsky J, Pursley R, Sathyamurthy A, Squair JW, Levi BP, Courtine G, Levine AJ. Single cell atlas of spinal cord injury in mice reveals a pro- regenerative signature in spinocerebellar neurons. Nat Commun. 2022 Sep 26;13(1):5628. doi:
Dobrott C, Sathyamurthy A, Levine AJ. Decoding Cell Type Diversity Within the Spinal Cord. Current Opinion in Physiology. 2019 Apr; 8:1-6
Dobrott C, Sathyamurthy A, Levine AJ. Decoding Cell Type Diversity Within the Spinal Cord. Current Opinion in Physiology. 2019 Apr; 8:1-6
This review by Dobrott et al. summarizes recent advances in the identification of mammalian spinal cord neuronal cell types and highlights the power of transcriptional profiling to identify and characterize the cell types of the spinal cord.
Matson KJE, Sathyamurthy A, Johnson KR, Kelly MC, Kelley MW, Levine AJ. Isolation of Adult Spinal Cord Nuclei for Massively Parallel Single-nucleus RNA Sequencing. J Vis Exp. 2018 Oct; (140).
Matson KJE, Sathyamurthy A, Johnson KR, Kelly MC, Kelley MW, Levine AJ. Isolation of Adult Spinal Cord Nuclei for Massively Parallel Single-nucleus RNA Sequencing. J Vis Exp. 2018 Oct; (140).
In this video article, Matson et al. present a high-throughput protocol for rapid isolation of nuclei for downstream snRNA-Seq. This method enables isolation of nuclei from fresh or frozen spinal cord samples and can be combined with two massively parallel droplet encapsulation platforms.
Barik A, Sathyamurthy A, Thompson J, Seltzer M, Levine AJ, Chesler AT. A spinoparabrachial circuit defined by Tacr1 expression drives pain (Elife)
Barik A, Sathyamurthy A, Thompson J, Seltzer M, Levine AJ, Chesler AT. A spinoparabrachial circuit defined by Tacr1 expression drives pain (Elife)
In this study, Barik et al describe a pathway from spinal cord to brain for ongoing pain.
Development and maintenance of the neuromuscular junction (studies that Dr Sathyamurthy contributed to in her post-doctoral and doctoral labs)
Development and maintenance of the neuromuscular junction (studies that Dr Sathyamurthy contributed to in her post-doctoral and doctoral labs)
How are synapse formed and maintained? This question is especially important at the neuro-muscular junction (NMJ), which often disintegrates in patients suffering from debilitating muscular dystrophic disease like congenital myasthenic syndrome causing muscular weakness and fatigue. In this series of studies, the authors address the cellular and molecular mechanisms underlying the formation and maintenance of the NMJ.
How are synapse formed and maintained? This question is especially important at the neuro-muscular junction (NMJ), which often disintegrates in patients suffering from debilitating muscular dystrophic disease like congenital myasthenic syndrome causing muscular weakness and fatigue. In this series of studies, the authors address the cellular and molecular mechanisms underlying the formation and maintenance of the NMJ.
Barik A, Li L, Sathyamurthy A, Xiong WC, Mei L. Schwann Cells in Neuromuscular Junction Formation and Maintenance. J Neurosci. 2016 Sep; 36(38):9770-81.
Barik A, Li L, Sathyamurthy A, Xiong WC, Mei L. Schwann Cells in Neuromuscular Junction Formation and Maintenance. J Neurosci. 2016 Sep; 36(38):9770-81.
In this study, the authors demonstrate that Schwann cells, the glial component of the tripartite NMJ, are critical not only for the development but also the maintenance of NMJs
Wu H, Barik A, Lu Y, Shen C, Bowman A, Li L, Sathyamurthy A, Lin TW, Xiong WC, Mei L. Slit2 as a β-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation. Elife. 2015 Jul; 4.
Wu H, Barik A, Lu Y, Shen C, Bowman A, Li L, Sathyamurthy A, Lin TW, Xiong WC, Mei L. Slit2 as a β-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation. Elife. 2015 Jul; 4.
Here the authors show that Slit2, a muscle-derived factor, is necessary for the formation of a functional synapse.
Barik A, Lu Y, Sathyamurthy A, Bowman A, Shen C, Li L, Xiong WC, Mei L. LRP4 is critical for neuromuscular junction maintenance. J Neurosci. 2014 Oct; 34(42):13892-905.
Barik A, Lu Y, Sathyamurthy A, Bowman A, Shen C, Li L, Xiong WC, Mei L. LRP4 is critical for neuromuscular junction maintenance. J Neurosci. 2014 Oct; 34(42):13892-905.
The authors show that Lrp4, a membrane bound receptor protein is essential for maintaining structural and functional integrity of the NMJ and that loss of muscle Lrp4 in adulthood alone is sufficient to cause myasthenic syndromes.
Is Lrp4 important only for NMJ formation and maintenance? No. Turns out Lrp4 is also essential for modulating glutamatergic transmission and adult neurogenesis in the brain.
Is Lrp4 important only for NMJ formation and maintenance? No. Turns out Lrp4 is also essential for modulating glutamatergic transmission and adult neurogenesis in the brain.
Sun XD, Li L, Liu F, Huang ZH, Bean JC, Jiao HF, Barik A, Kim SM, Wu H, Shen C, Tian Y, Lin TW, Bates R, Sathyamurthy A, Chen YJ, Yin DM, Xiong L, Lin HP, Hu JX, Li BM, Gao TM, Xiong WC, Mei L. Lrp4 in astrocytes modulates glutamatergic transmission. Nat Neurosci. 2016 Aug; 19(8):1010-8.
Zhang H, Sathyamurthy A, Liu F, Li L, Zhang L, Dong Z, Cui W, Sun X, Zhao K, Wang H, Ho HH,Xiong WC, Mei L. Agrin-Lrp4-Ror2 signaling regulates adult hippocampal neurogenesis in mice. Elife.2019 Jul 3;8
Synapse development and function
Synapse development and function
(studies that Dr Sathyamurthy contributed to in her post-doctoral and doctoral labs)
(studies that Dr Sathyamurthy contributed to in her post-doctoral and doctoral labs)
In the following studies, the authors address the role of Nrg and Erbb4, genes that have been implicated in schizophrenia, in regulating synapse development and function.
In the following studies, the authors address the role of Nrg and Erbb4, genes that have been implicated in schizophrenia, in regulating synapse development and function.
Yin DM, Chen YJ, Liu S, Jiao H, Shen C, Sathyamurthy A, Lin TW, Xiong WC, Li BM, Mei L, Bergson C. Calcyon stimulates neuregulin 1 maturation and signaling. Molecular Psychiatry. 2015 Oct; 20: 1251– 1260
Bean JC, Lin TW, Sathyamurthy A, Liu F, Yin DM, Xiong WC, Mei L. Genetic labeling reveals novel cellular targets of schizophrenia susceptibility gene: distribution of GABA and non-GABA ErbB4-positive cells in adult mouse brain. J Neurosci. 2014 Oct; 34(40):13549-66.
Yin DM, Sun XD, Bean JC, Lin TW, Sathyamurthy A, Xiong WC, Gao TM, Chen YJ, Mei L. Regulation of spine formation by ErbB4 in PV-positive interneurons. J Neurosci. 2013 Dec; 33(49):19295-303.
Yin DM, Chen YJ, Lu YS, Bean JC, Sathyamurthy A, Shen C, Liu X, Lin TW, Smith CA, Xiong WC, Mei L. Reversal of behavioral deficits and synaptic dysfunction in mice overexpressing neuregulin 1. Neuron. 2013 May; 78(4):644-57.
Yin DM, Chen YJ, Sathyamurthy A, Xiong WC, Mei L. Synaptic dysfunction in schizophrenia. Adv Exp Med Biol. 2012; 970:493-516.
Rosenthal JS, Yin J, Lei J, Sathyamurthy A, Short J, Long C, Spillman E, Sheng C, and Yuan Q, Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development in Drosophila, PNAS June 8, 2021 118 (23) e2004685118
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