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Research Overview

The goal of our laboratory is to understand the mechanisms that underlie synaptic and circuit plasticity in the developing and mature mammalian central nervous system. We use a combination of tools, including electrophysiological, in vitro and in vivo optical imaging methods, along with genetically altered mouse strains, optogenetics and pharmacogenetics to examine the regulation of synaptic circuits in the visual system.

One area of our research focuses on the establishment and refinement of synaptic circuits during development. We have characterized, using electrophysiological techniques, the convergence of the retinogeniculate synapse during development as multiple inputs are eliminated and remaining synaptic inputs strengthened. In addition, we have uncovered an experience-dependent critical period at this synapse during which connections can be re-wired late in development. Our recent studies show that cortical feedback regulates plasticity of this feedforward pathway. To identify and characterize the factors that mediate the different phases of remodeling of the retinogeniculate synapse, we are taking advantage of mouse mutants and viral-mediated circuit manipulations to elucidate the roles of specific molecular cues and plasticity mechanisms. These approaches are also used to advance our understanding of how disruption of proper synaptic circuit development can lead to neurodevelopmental disorders such as autism spectrum disorders, intellectual disabilities and epilepsy.

In another line of research, we are interested in understanding the mechanisms that regulate how firing patterns of retinal cells are decoded into the output of the thalamocortical neurons. These mechanisms are especially important during development, in the face of dramatic changes in strength and connectivity. We are addressing several questions: (1) how do specific retinal firing patterns influence synaptic strength through presynaptic and postsynaptic mechanisms, (2) how do ascending neurotransmitter systems from the brainstem and feedback circuits from the cortex and thalamic reticular nucleus alter the strength of the retinogeniculate synapse and sensory processing, and (3) how do long-term changes in presynaptic activity alter the properties of the retinogeniculate synapse.

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Researcher Areas

  • Synaptic Plasticity

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PUBLICATIONS

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  1. Thompson AD, Picard N, Min L, Fagiolini M, Chen C. Cortical Feedback Regulates Feedforward Retinogeniculate Refinement. Neuron. 2016 Sep 07; 91(5):1021-1033. View abstract
  2. Chen C, Bickford ME, Hirsch JA. Untangling the Web between Eye and Brain. Cell. 2016 Mar 24; 165(1):20-21. View abstract
  3. Iwase S, Brookes E, Agarwal S, Badeaux AI, Ito H, Vallianatos CN, Tomassy GS, Kasza T, Lin G, Thompson A, Gu L, Kwan KY, Chen C, Sartor MA, Egan B, Xu J, Shi Y. A Mouse Model of X-linked Intellectual Disability Associated with Impaired Removal of Histone Methylation. Cell Rep. 2016 Feb 09; 14(5):1000-1009. View abstract
  4. Bei F, Lee HHC, Liu X, Gunner G, Jin H, Ma L, Wang C, Hou L, Hensch TK, Frank E, Sanes JR, Chen C, Fagiolini M, He Z. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell. 2016 Jan 14; 164(1-2):219-232. View abstract
  5. Hong YK, Park S, Litvina EY, Morales J, Sanes JR, Chen C. Refinement of the retinogeniculate synapse by bouton clustering. Neuron. 2014 Oct 22; 84(2):332-9. View abstract
  6. Hauser JL, Liu X, Litvina EY, Chen C. Prolonged synaptic currents increase relay neuron firing at the developing retinogeniculate synapse. J Neurophysiol. 2014 Oct 01; 112(7):1714-28. View abstract
  7. Louros SR, Hooks BM, Litvina L, Carvalho AL, Chen C. A role for stargazin in experience-dependent plasticity. Cell Rep. 2014 Jun 12; 7(5):1614-1625. View abstract
  8. Lin DJ, Kang E, Chen C. Changes in input strength and number are driven by distinct mechanisms at the retinogeniculate synapse. J Neurophysiol. 2014 Aug 15; 112(4):942-50. View abstract
  9. Chung WS, Clarke LE, Wang GX, Stafford BK, Sher A, Chakraborty C, Joung J, Foo LC, Thompson A, Chen C, Smith SJ, Barres BA. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature. 2013 Dec 19; 504(7480):394-400. View abstract
  10. Kang E, Durand S, LeBlanc JJ, Hensch TK, Chen C, Fagiolini M. Visual acuity development and plasticity in the absence of sensory experience. J Neurosci. 2013 Nov 06; 33(45):17789-96. View abstract
  11. Hauser JL, Edson EB, Hooks BM, Chen C. Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse. J Neurophysiol. 2013 Jan; 109(1):113-23. View abstract
  12. Noutel J, Hong YK, Leu B, Kang E, Chen C. Experience-dependent retinogeniculate synapse remodeling is abnormal in MeCP2-deficient mice. Neuron. 2011 Apr 14; 70(1):35-42. View abstract
  13. Hong YK, Chen C. Wiring and rewiring of the retinogeniculate synapse. Curr Opin Neurobiol. 2011 Apr; 21(2):228-37. View abstract
  14. Hooks BM, Chen C. Vision triggers an experience-dependent sensitive period at the retinogeniculate synapse. J Neurosci. 2008 Apr 30; 28(18):4807-17. View abstract
  15. Liu X, Chen C. Different roles for AMPA and NMDA receptors in transmission at the immature retinogeniculate synapse. J Neurophysiol. 2008 Feb; 99(2):629-43. View abstract
  16. Hooks BM, Chen C. Critical periods in the visual system: changing views for a model of experience-dependent plasticity. Neuron. 2007 Oct 25; 56(2):312-26. View abstract
  17. Paradis S, Harrar DB, Lin Y, Koon AC, Hauser JL, Griffith EC, Zhu L, Brass LF, Chen C, Greenberg ME. An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development. Neuron. 2007 Jan 18; 53(2):217-32. View abstract
  18. Hooks BM, Chen C. Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse. Neuron. 2006 Oct 19; 52(2):281-91. View abstract
  19. Flavell SW, Cowan CW, Kim TK, Greer PL, Lin Y, Paradis S, Griffith EC, Hu LS, Chen C, Greenberg ME. Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science. 2006 Feb 17; 311(5763):1008-12. View abstract
  20. Seeburg DP, Liu X, Chen C. Frequency-dependent modulation of retinogeniculate transmission by serotonin. J Neurosci. 2004 Dec 01; 24(48):10950-62. View abstract
  21. Chen C, Regehr WG. Presynaptic modulation of the retinogeniculate synapse. J Neurosci. 2003 Apr 15; 23(8):3130-5. View abstract
  22. Chen C, Blitz DM, Regehr WG. Contributions of receptor desensitization and saturation to plasticity at the retinogeniculate synapse. Neuron. 2002 Feb 28; 33(5):779-88. View abstract
  23. Carter AR, Chen C, Schwartz PM, Segal RA. Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure. J Neurosci. 2002 Feb 15; 22(4):1316-27. View abstract