James M. Tepper

Tango Therapeutics (United States)

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Giannicola Genovese

The University of Texas MD Anderson Cancer Center

Lynda Chin

Dana-Farber Cancer Institute

Li Li

Sun Yat-sen University Cancer Center

Tony Gutschner

Martin Luther University Halle-Wittenberg

Ian R. Watson

McGill University

Guocan Wang

The University of Texas MD Anderson Cancer Center

Peter K. Cabeceiras

Massachusetts Institute of Technology

Gordon B. Mills

Oregon Health & Science University

Zhuangna Fang

The University of Texas MD Anderson Cancer Center

Mozhdeh Mahdavi

The University of Texas MD Anderson Cancer Center

Cooperative Institutions

The University of Texas MD Anderson Cancer Center

Rutgers, The State University of New Jersey

Tango Therapeutics (United States)

Harvard University

National Institutes of Health

The University of Texas Health Science Center at Houston

Johns Hopkins University

Centre National de la Recherche Scientifique

Rutgers Sexual and Reproductive Health and Rights

University of California, Los Angeles

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Functional Roles of Dopamine D₂and D₃Autoreceptors on Nigrostriatal Neurons Analyzed by Antisense KnockdownIn Vivo

Journal of Neuroscience (1997)

James M. Tepper Bao-Cun Sun Lynn P. Martin Ian Creese

Two different 19-mer antisense oligodeoxynucleotides complementary to the initial coding regions of dopamine D 2 or D 3 receptor mRNA were infused unilaterally into the substantia nigra of rats for 3–6 d to suppress synthesis of D 2 and/or D 3 receptors on substantia nigra dopaminergic neurons, thereby producing specific reductions of D 2 and/or D 3 receptors. Autoradiographic receptor binding revealed that D 2 and D 3 antisense oligodeoxynucleotides specifically and significantly reduced D 2 or D 3 binding in the ipsilateral substantia nigra, respectively, without affecting dopamine receptor binding in the neostriatum. Either D 2 or D 3 antisense oligodeoxynucleotides greatly attenuated the ability of apomorphine to inhibit dopaminergic neurons in vivo , an effect that was potentiated by simultaneous administration of D 2 and D 3 antisenses. Despite these effects, neither the rate nor the pattern of spontaneous activity of antisense-treated nigrostriatal neurons differed from those in the control groups. The proportion of antidromic responses consisting of full spikes from antisense-treated rats was significantly greater, and the mean antidromic threshold was significantly lower than in controls, indicating that autoreceptor knockdown increased both somatodendritic and terminal excitability. These data demonstrate that selective reduction of specific dopamine receptor subtypes by antisense infusion can be effected in vivo , and that nigrostriatal neurons express both D 2 and D 3 autoreceptors at their somatodendritic and axon terminal regions. Although the somatodendritic and terminal autoreceptors modulate dendritic and terminal excitability, respectively, the interaction of endogenously released dopamine with somatodendritic autoreceptors does not appear to exert a significant effect on spontaneous activity in anesthetized rats.

Autoreceptor

Antidromic

Nigrostriatal pathway

10.1523/jneurosci.17-07-02519.1997

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Citations (118)

Data Supplement from The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF

Ian R. Watson Li Li Peter K. Cabeceiras Mozhdeh Mahdavi Tony Gutschner

<p>Supplementary Table 4. STR profiles for cell lines used in this study.</p>

Hotspot (geology)

10.1158/0008-5472.22404077

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Citations (0)

Data Supplement from The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF

Ian R. Watson Li Li Peter K. Cabeceiras Mozhdeh Mahdavi Tony Gutschner

<p>Supplementary Figure 4: Overexpression of RAC1 P29S increases cell viability of A375 to RAF and MEK inhibitor treatment.</p>

10.1158/0008-5472.22404089.v1

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Citations (0)

Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer

Nature (2017)

Giannicola Genovese Alessandro Carugo James M. Tepper Frederick S. Robinson Li Li

Reprogramming

10.1038/nature21064

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Citations (114)

Striatal, pallidal, and pars reticulata evoked inhibition of nigrostriatal dopaminergic neurons is mediated by GABAA receptors in vivo

Neuroscience (1999)

Carlos A. Paladini Pau Celada James M. Tepper

Medium spiny neuron

Pars reticulata

GABA receptor antagonist

10.1016/s0306-4522(98)00355-8

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Citations (145)

Postnatal development of the electrical activity of rat nigrostriatal dopaminergic neurons

Developmental Brain Research (1990)

James M. Tepper Francine Trent Shôji Nakamura

Antidromic

Orthodromic

Bursting

10.1016/0165-3806(90)90061-3

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Citations (81)

Dual Cholinergic Control of Fast-Spiking Interneurons in the Neostriatum

Journal of Neuroscience (2002)

Tibor Koós James M. Tepper

GABAergic interneurons appear to play a fundamental role in the functioning of the neostriatum by modulating the spiking of striatal projection neurons with great efficacy. The powerful and strongly divergent output of the GABAergic interneurons neurons suggests that modulation of their activity may be particularly effective at controlling the functioning of the entire neostriatal circuitry. Acetylcholine is one of the main modulators of striatal functioning. The effects of acetylcholine on fast-spiking (FS) GABAergic interneurons were studied with whole-cell recording in an in vitro slice preparation. Acetylcholine exerted two distinct effects on fast-spiking interneurons. Acetylcholine directly depolarized FS interneurons by acting on nondesensitizing soma-dendritic nicotinic receptors. In addition, acetylcholine attenuated the GABAergic inhibition of projection neurons by fast-spiking interneurons through activation of presynaptic muscarinic receptors. It is suggested that the nicotinic excitation of FS interneurons may play an important role in translating the effect of the brief behaviorally contingent cessation of firing of the tonically active cholinergic interneurons to the output neurons of the neostriatum. In contrast, the muscarinic presynaptic inhibitory mechanism may be engaged primarily during longer-lasting elevations of extracellular acetylcholine levels.

Interneuron

10.1523/jneurosci.22-02-00529.2002

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Citations (294)

Opposing Influence of Sensory and Motor Cortical Input on Striatal Circuitry and Choice Behavior

bioRxiv (Cold Spring Harbor Laboratory) (2018)

Christian Lee Alex J. Yonk Joost Wiskerke Kenneth G. Paradiso James M. Tepper

Summary The striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1- or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry.

Medium spiny neuron

10.1101/446708

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Citations (1)

GABAA receptor stimulation blocks NMDA-induced bursting of dopaminergic neurons in vitro by decreasing input resistance

Brain Research (1999)

Carlos A. Paladini Yuji Iribe James M. Tepper

Bursting

10.1016/s0006-8993(99)01484-5

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Citations (67)

Cerebellar-responsive neurons in the thalamic ventroanterior-ventrolateral complex of rats: In vivo electrophysiology