Joshua L. Plotkin

At any given moment, our brain is confronted with the daunting task of sorting through a plethora of potential actions that can be performed.  Some of these actions are useful and appropriate, and should be green lit.  Others are inappropriate, and must be suppressed.  The brain has several strategies to streamline this process, one being habit learning- through repetition, the brain can learn to initiate an automatic response based on what has worked in the past and what has not.  The inability to properly do this is at the crux of many neurological disorders- perhaps most notably, obsessive compulsive disorder (OCD). Our lab’s research focuses on the part of the brain most intimately associated with this type of action selection and habit learning: the basal ganglia.  The major input nucleus of the basal ganglia, the striatum, is charged with receiving massive amounts of information from wildly diverse parts of the brain.  The striatum sorts and integrates this synaptic information and then passes it on to the output nuclei of the basal ganglia, which ultimately make a recommendation about which actions should be performed.

We are interested in understanding how the striatum accomplishes this, and what goes awry in disease states.  We use cutting edge physiological and imaging techniques to dissect the microcircuitry of the striatum, ask how specific synaptic connections within this circuit are plastically adjusted to optimize behavior, and determine how this is altered in neurological disorders such as OCD.  To do this, we pair electrophysiological recordings with 2-photon laser scanning microscopy to record from identified striatal neurons in genetically altered mice.  We probe the local activity of postsynaptic dendritic sub-regions using 2-photon calcium imaging, and activate individual, visually identified synapses using 2-photon photolysis of glutamate and optogenetic activation of specific afferents.  The combination of these tools lets us interrogate the striatum in a way that has traditionally not been possible, and opens exciting new doors to uncover the underpinnings of disorders such as OCD.

• Selected Publications

  Prager, E.M., Dorman, D.B., Hobel, Z.B., Malgady, J.M., Blackwell, K.T. and Plotkin, J.L.  (2020).  Dopamine oppositely modulates state transitions in striosome and matrix direct pathway striatal spiny neurons.  Neuron. 108(6):1091-1102.

  Cirnaru, M.D., Melis, C., Fanutza, T., Naphade, S., Tshilenge, K.N., Muntean, B.S., Martemyanov, K.A., Plotkin, J.L., Ellerby, L.M. and Ehrlich, M.E. (2019).  Nuclear receptor Nr4a1 regulates striatal striosome development and dopamine D1 receptor signaling.  eNeuro. 6(5): ENEURO.0305-19.2019.

  Prager, E.M. and Plotkin, J.L. (2019).  Compartmental function and modulation of the striatum.  Journal of Neuroscience Research. 97(12):1503-1514. 

  Plotkin, J.L. and Goldberg, J.A. (2019).  Thinking outside the box (and arrow): current themes in striatal dysfunction in movement disorders. The Neuroscientist. 25(4):359-79.  PMID: 30379121.

  Plotkin, J.L. and Surmeier, D.J. (2015). Corticostriatal synaptic adaptations in Huntington’s disease. Current Opinion in Neurobiology. 33:53-62.

  Fieblinger, T., Graves, S., Sebel, L., Alcacer, C., Plotkin, J.L., Gertler, T., Chan, C.S., Heiman, M., Greengard, P., Cenci, M.A. and Surmeier, D.J. (2014). Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia. Nature Communications. 5:5316.

  Plotkin, J.L. and Surmeier, D.J. (2014). Impaired striatal function in Huntington’s disease is due to aberrant p75NTR signaling. Rare Diseases. DOI 10.4161/2167549X.2014.968482.

  Plotkin, J.L., Day, M., Peterson, J.D., Xie, Z., Kress, G.J., Rafalovich, R., Gertler, T.S., Flajolet, M., Greengard, P., Stavarache, M., Kaplitt, J.G., Chan, C.S. and Surmeier, D.J. (2014). Impaired TrkB receptor signaling underlies corticostriatal synaptic dysfunction in Huntington’s disease. Neuron. 83(1):178-8.

  Plotkin, J.L. and Surmeier, D.J. (2014). Optical approaches for studying dendritic excitability. For “Patch Clamp Methods and Protocols”, co-ed. S. Taverna. 1183:171-82.

  Tan, C.L., Plotkin, J.L., Veno, M.T., von Schimmelmann, M., Feinberg, P., Mann, S., Handler, A., Kjems, J., Surmeier, D.J., O’Carroll, D., Greengard, P. and Schaefer, A. (2013). MicroRNA miR-128 governs neuronal excitability and motor behavior in mice. Science. 342(6163):1254-8

  Plotkin, J.L., Shen, W., Rafalovich, I., Sebel, L.E., Day, M., Chan, C.S. and Surmeier, D.J. (2013). Regulation of dendritic calcium release in striatal spiny projection neurons. Journal of Neurophysiology. 110(10):2325-36

  Chan, C.S., Peterson, J.D., Gertler, T., Glajch, K.E., Quintana, R.E., Cui, Q., Sebel, L.E., Plotkin, J.L., Shen, W., Heiman, M., Heintz, N., Greengard, P. and Surmeier, D.J. (2012). Strain-specific regulation of striatal phenotype in Drd2-eGFP BAC transgenic mice. The Journal of Neuroscience. 32(27):9124-32

  Plotkin, J.L., Day, M. and Surmeier, D.J. (2011). Synaptically driven state transitions in distal dendrites of striatal spiny neurons. Nature Neuroscience. 14(7):881-8

  Surmeier, D.J., Plotkin, J., Shen, W. (2009). Dopamine and synaptic plasticity in dorsal striatal circuits controlling action selection. Current Opinion in Neurobiology. 19:621-628

  Day, M., Wokosin, D., Plotkin, J.L., Tian, X., Surmeier, D.J. (2008). Differential excitability and modulation of striatal medium spiny neuron dendrites. The Journal of Neuroscience. 28(45):11603-14

  Plotkin, J.L., Wu, N., Chesselet, M-F and Levine, M.S. (2005). Functional and molecular development of striatal fast- spiking GABAergic interneurons and their cortical inputs. European Journal of Neuroscience. 22:1097-1108

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