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Research Overview

The formation and refinement of synaptic circuits are fundamental to neurological function. The Chen lab has been dedicated to understanding the mechanisms underlying this process in the developing mammalian central nervous system. While much is known about plasticity in the hippocampus and cortex, little attention has been focused on other regions of the brain that are critical in cognition and disease. Our studies have focused on the thalamus, a subcortical region important for the processing and relay of information targeted to different areas of the cortex. The thalamus regulates consciousness, sleep, and alertness, yet how thalamic circuits develop and how disruption of these circuits contributes to neurodevelopmental and neuropsychiatric disorders are poorly understood. Our hope is that the knowledge gained from our studies will inform new therapeutic approaches for neurodevelopmental disorders such as autism, mental retardation, epilepsy, schizophrenia and bipolar disease.

We use the visual system as our experimental model as it is the premier system to probe the mechanisms and logic of neuronal circuit refinement over development. Sensory information can be easily manipulated, and resultant outputs monitored quantitatively with electrophysiological, anatomical and behavioral assays. We study the connection between retinal ganglion cells (RGCs) in the eye and relay neurons in the dorsolateral geniculate nucleus (dLGN, the visual thalamus) of mice, a synapse that shows robust synaptic plasticity during development. RGC axons initially map diffusely onto dLGN and then segregate into eye-specific layers by the removal of axon segments in incorrect layers. However, even after eye-specific layers are formed, retinogeniculate connections within the same layer continue to undergo a process of robust synapse elimination and strengthening (collectively referred to as synapse remodeling) to produce the precise connectivity that determines a mature thalamocortical neuron’s receptive field. Our research has revealed significant plasticity in the thalamus, a major relay station for most sensory information transmitted to the cortex. Furthermore, our studies have demonstrated that the thalamus plays a significant role in integrating and transforming the representations of information that come from the retina, a role previously attributed solely to the cortex.

About Chinfei Chen

Chinfei Chen received her M.D. and Ph.D. from Harvard Medical School and completed her internship and residency in adult Neurology at Massachusetts General Hospital. She trained as a postdoctoral fellow with Dr. Roderick MacKinnon and later with Dr. Wade Regehr. She has received numerous awards including a Mentored Clinical Scientist Development Award and Pew Scholars Program in the Biomedical Sciences.

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  • 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