My laboratory studies the synaptic mechanisms that underlie developmental synapse remodeling and contribute to the processing of information in the immature and mature central nervous system. Our goal is to understand the role of plasticity in normal development, and how disruption of normal plasticity leads to neurodevelopmental disorders. We use the retinogeniculate synapse as a model for our studies of synapse plasticity. This synapse connects neurons in the retina to neurons in the thalamus--a deep brain structure that relays incoming sensory information to the cortex.
In one line of investigation, we are studying the factors that are important in the formation and refinement of synaptic connections during development. We have found that developmental synaptic plasticity at the retinogeniculate synapse occurs over a much longer time scale than previously recognized. Our studies show two robust phases of synaptic remodeling, the first dependent on spontaneous activity, the other, previously unrecognized, on sensory experience. Using a candidate gene approach, we are screening for molecules that regulate the two different phases of synaptic plasticity.
One mutant animal from the screen that exhibits a disruption in plasticity is a mouse lacking the transcriptional regulator MeCP2; this mutant is used to model Rett syndrome. We find that the strength and number of retinal-ganglion-cell inputs onto geniculate neurons in these mice are comparable to those of wild-type littermates during the first phase of synapse refinement, indicating that initial stages of synapse formation, elimination and strengthening are not significantly affected by MeCP2 absence.
However, during the later, experience-dependent phase of synapse remodeling, the circuit becomes abnormal in the mutant mice as retinal innervation of relay neurons increases and retinal inputs fail to strengthen further. Moreover, synaptic plasticity in response to visual deprivation is diminished in the mutants. These results suggest a crucial role for MeCP2 in experience-dependent refinement of synaptic circuits.
In another line of research, we are investigating the mechanisms that regulate how firing patterns of retinal cells are decoded into the output of the thalamo-cortical neurons. These mechanisms are especially important during development, when there are dramatic changes in strength and connectivity.
We found that several features of the immature synapse are different from the mature synapse and contribute to synaptic transmission--including asynchronous release, neurotransmitter spillover and the prolonged time course of NMDA receptor currents. These properties enable immature synapses to contribute to the firing of postsynaptic relay neurons. Our results suggest that the properties of the glutamate receptors and intrinsic membrane conductances at the retinogeniculate synapse are finely matched to the "maturity" of the connection to ensure the transmission of information over development.
About Chinfei Chen
Chinfei Chen received an MD/PhD from the Harvard/MIT Division of Health Sciences and Technology. She trained in adult neurology at Massachusetts General Hospital and as a postdoctoral fellow in the Neurobiology Department at Harvard Medical School before joining the faculty at Children's Hospital Boston. Chen was a 2001 Pew Scholar in the Biomedical Sciences.
Hooks BM, Chen C. Vision triggers an experience-dependent sensitive period at the retinogeniculate synapse. J Neurosci 2008 Apr 30; 28(18):4807-17.
Liu X, Chen C. Differential Roles for AMPA and NMDA Receptors in at the Immature Retinogeniculate Synapse. J Neurophysiology 2008; 99:629-43.
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.
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.
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.
Hooks BM and Chen C. A model for synaptic refinement in visual thalamus. In: Erzurumlu R et al, eds. Development and Plasticity in Sensory Thalamus and Cortex. 2006. Springer Science+ Business Media, LL.
Seeburg DP, Liu X, Chen C. Frequency-dependent modulation of retinogeniculate transmission by serotonin. J Neurosci 2004; 24:10950-62.
For a list of Chinfei Chen's publications on PubMed, click here.