Our Publications

Heterogeneity of retinogeniculate axon arbors

Y. Kate Hong, Eliza F. Burr, Joshua R. Sanes, and Chinfei Chen

European Journal of Neuroscience, Vol. 49, pp. 948–956, 2019

The retinogeniculate synapse transmits information from retinal ganglion cells (RGC) in the eye to thalamocortical relay neurons in the visual thalamus, the dorsal lateral geniculate nucleus (dLGN). Studies in mice have identified genetic markers for distinct classes of RGCs encoding different features of the visual space, facilitating the dissection of RGC subtype-specific physiology and anatomy. In this study, we examine the morphological properties of axon arbors of the BD-RGC class of ON-OFF direction selective cells that, by definition, exhibit a stereotypic dendritic arbor and termination pattern in the retina. We find that axon
arbors from the same class of RGCs exhibit variations in their structure based on their target region of the dLGN. Our findings suggest that target regions may influence the morphologic and synaptic properties of their afferent inputs.

A Fine Scale Functional Logic to Convergence from Retina to Thalamus

Liang Liang, Alex Fratzl, Glenn Goldley, Rohan N. Ramesh, Arthur U. Sugden, Josh L. Morgan, Chinfei Chen, Mark L. Andermann

Cell, 31 May 2018, Volume 173, Issue 6

Numerous well-defined classes of retinal ganglion cells innervate the thalamus to guide image-forming vision, yet the rules governing their convergence and divergence remains unknown. Using two-photon imaging in awake mouse thalamus, we observed a functional arrangement of retinal ganglion cell axonal boutons in which coarse-scale retinotopic ordering gives way to fine-scale organization based on shared preferences for other visual features. Specifically, at the ~6 μm scale, clusters of boutons from different axons often showed similar preferences for either one or multiple features, including axis and direction of motion, spatial frequency, and changes in luminance. Conversely, individual axons could "de-multiplex" information channels by participating in multiple, functionally distinct...

Visual Experience-Dependent Expression of Fn14 Is

Required for Retinogeniculate Refinement

 Lucas Cheadle, Christopher P. Tzeng,

Brian T. Kalish, ..., Linda C. Burkly,

Chinfei Chen, Michael E. Greenberg

Neuron, 8 August 2018, Volume 99

 Sensory experience influences the establishment of

neural connectivity through molecular mechanisms

that remain unclear. Here, we employ single-nucleus

RNA sequencing to investigate the contribution of

sensory-driven gene expression to synaptic refinement

in the dorsal lateral geniculate nucleus of the

thalamus, a region of the brain that processes visual

information. We find that visual experience induces

the expression of the cytokine receptor Fn14 in

excitatory thalamocortical neurons. By combining

electrophysiological and structural techniques, we

show that Fn14 is dispensable for early phases of

refinement mediated by spontaneous activity but

that Fn14 is essential for refinement during a

later, experience-dependent period of development.

Refinement deficits in mice lacking Fn14 are associated

with functionally weaker and structurally smaller

retinogeniculate inputs...

Functional Convergence at the Retinogeniculate Synapse

Elizabeth Y. Litvina and Chinfei Chen
Neuron 96, 11 October 2017, Volume 4, Issue 1

Precise connectivity between retinal ganglion cells (RGCs) and thalamocortical (TC) relay neurons is thought to be essential for the transmission of visual information. Consistent with this view, electrophysiological measurements have previously estimated that 1–3 RGCs converge onto a mouse geniculate TC neuron. Recent advances in connectomics and rabies tracing have yielded much higher estimates of retinogeniculate convergence, although not all identified contacts may be functional. Here we use optogenetics and a computational simulation to determine the number of functionally relevant retinogeniculate inputs onto TC neurons in mice. We find an average of ten RGCs converging onto a mature TC neuron, in contrast to >30 inputs before developmental refinement. However, only 30% of retinogeniculate inputs exceed the threshold for dominating postsynaptic activity. These results signify a greater role for the thalamus in visual processing and provide a functional perspective of anatomical connectivity data.

The Importance of Constructive Feedback: Implications of Top Down Regulation in the Development of Neural Circuits

Andrew D. Thompson and Chinfei Chen
Neurogenesis, 3 March 2017, Volume 4, Issue 1

Neural circuits in sensory pathways develop through a general strategy of overproduction of synapses followed by activity-driven pruning to fine-tune connectivity for optimal function. The early visual pathway, consisting of the retina!visual thalamus!primary visual cortex, has served for decades as a powerful model system for probing the mechanisms and logic of this process. In addition to these feedforward projections, the early visual pathway also includes a substantial feedback component in the form of corticothalamic projections from the deepest layer of primary visual cortex...

Cortical Feedback Regulates Feedforward Retinogeniculate Refinement

Andrew D. Thompson, Nathalie Picard, Lia Min, Michela Fagiolini, Chinfei Chen
Neuron, 7 September 2016, Volume 91, Issue 5, 1021-1033

According to the prevailing view of neural development, sensory pathways develop sequentially in a feedforward manner, whereby each local microcircuit refines and stabilizes before directing the wiring of its downstream target. In the visual system, retinal circuits are thought to mature first and direct refinement in the thalamus, after which cortical circuits refine with experience-dependent plasticity. In contrast, we now show that feedback from cortex to thalamus critically regulates refinement of the retinogeniculate projection during a discrete window in development, beginning at postnatal day 20 in mice...

Restoration of Visual Function by Enhancing Conduction in Regenerated Axons

Bei F, Lee HH, Liu X, Gunner G, Jin H, Ma L, Wang C, Hou L, Hensch TK, Frank E, Sanes JR, Chen C, Fagiolini M, He Z.
Cell, 14 January 2016, Volume 164, Issue 1-2, 219-32

Although a number of repair strategies have been shown to promote axon outgrowth following neuronal injury in the mammalian CNS, it remains unclear whether regenerated axons establish functional synapses and support behavior. Here, in both juvenile and adult mice, we show that either PTEN and SOCS3 co-deletion, or co-overexpression of osteopontin (OPN)/insulin-like growth factor 1 (IGF1)/ciliary neurotrophic factor (CNTF), induces regrowth of retinal axons and formation of functional synapses in the superior colliculus (SC) but not significant recovery of visual function...

Untangling the Web between Eye and Brain

Chen C, Bickford ME, Hirsch JA
Cell, 24 March 2016, Volume 165, Issue 1, 20-21

How is the picture of the visual scene that the eye encodes represented by neural circuits in the brain? In this issue of Cell, Morgan et al. address this question by forming an ultrastructural “connectome” of the mouse’s visual thalamus that depicts individual retinal afferents and every contact these form with target relay cells

Refinement of the Retinogeniculate Synapse by Bouton Clustering

Y. Kate Hong, SuHong Park, Elizabeth Y. Litvina, Jose Morales, Joshua R. Sanes, Chinfei Chen
Neuron, 22 October 2014, Volume 84, Issue 2, 332–339

Mammalian sensory circuits become refined over development in an activity-dependent manner. Retinal ganglion cell (RGC) axons from each eye first map to their target in the geniculate and then segregate into eye-specific layers by the removal and addition of axon branches. Once segregation is complete, robust functional remodeling continues as the number of afferent inputs to each geniculate neuron decreases from many to a few. It is widely assumed that large-scale axon retraction underlies this later phase of circuit refinement. On the contrary, RGC axons remain stable during functional pruning...

Prolonged synaptic currents increase relay neuron firing at the developing retinogeniculate synapse

Jessica L. Hauser, Xiaojin Liu, Elizabeth Y. Litvina, Chinfei Chen
Journal of Neurophysiology, October 2014, Volume 112, Issue 7, 1714-1728

The retinogeniculate synapse, the connection between retinal ganglion cells (RGC) and thalamic relay neurons, undergoes robust changes in connectivity over development. This process of synapse elimination and strengthening of remaining inputs is thought to require synapse specificity. Here we show that glutamate spillover and asynchronous release are prominent features of retinogeniculate synaptic transmission during this period. The immature excitatory postsynaptic currents exhibit a slow decay time course that is sensitive to low-affinity glutamate receptor antagonists and extracellular calcium concentrations, consistent with glutamate spillover. Furthermore, we uncover and characterize a novel, purely spillover-mediated AMPA receptor current from immature relay neurons...

A Role for Stargazin in Experience-Dependent Plasticity

Susana R. Louros, Bryan M. Hooks, Liza Litvina, Ana Luisa Carvalho, Chinfei Chen
Cell Reports, 12 June 2014, Volume 7, Issue 5, 1614-1625

During development neurons are constantly refining their connections in response to changes in activity. Experience-dependent plasticity is a key form of synaptic plasticity, involving changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) accumulation at synapses. Here we report a critical role for the AMPAR auxiliary subunit, stargazin, in this plasticity. We show that stargazin is functional at the retinogeniculate synapse and that in the absence of stargazin, the refinement of the retinogeniculate synapse is specifically disrupted during the experience-dependent phase...

Changes in input strength and number are driven by distinct mechanisms at the retinogeniculate synapse

David J. Lin, Erin Kang, Chinfei Chen
Journal of Neurophysiology, August 2014, Volume 112, Issue 4, 942-950

Recent studies have demonstrated that vision influences the functional remodeling of the mouse retinogeniculate synapse, the connection between retinal ganglion cells and thalamic relay neurons in the dorsal lateral geniculate nucleus (LGN). Initially, each relay neuron receives a large number of weak retinal inputs. Over a 2- to 3-wk developmental window, the majority of these inputs are eliminated, and the remaining inputs are strengthened. This period of refinement is followed by a critical period when visual experience changes the strength and connectivity of the retinogeniculate synapse. Visual deprivation of mice by dark rearing from postnatal day (P)20 results in a dramatic weakening of synaptic strength and recruitment of additional inputs...

Visual acuity development and plasticity in the absence of sensory experience


Kang E, Durand S, LeBlanc JJ, Hensch TK, Chen C, Fagiolini M
Journal of Neuroscience,6 November 2013, Volume 33, Issue 45, 17789-17796

Visual circuits mature and are refined by sensory experience. However, significant gaps remain in our understanding how deprivation influences the development of visual acuity in mice. Here, we perform a longitudinal study assessing the effects of chronic deprivation on the development of the mouse subcortical and cortical visual circuits using a combination of behavioral optomotor testing, in vivo visual evoked responses (VEP) and single-unit cortical recordings. As previously reported, orientation tuning was degraded and onset of ocular dominance plasticity was delayed and remained open in chronically deprived mice....

Frequency-Dependent Modulation of Retinogeniculate Transmission by Serotonin

Daniel P. Seeburg, Xiaojin Liu, Chinfei Chen
The Journal of Neuroscience, 1 December 2004, Volume 24, Issue 48, 10950-10962

The relay of visual information converging in the lateral geniculate nucleus (LGN) en route to the visual cortex is modulated by projections from brainstem nuclei. The release of serotonin, one mediator of these effects, has been shown to act at a presynaptic site to inhibit neurotransmitter release at the retinogeniculate synapse, the connection between retinal ganglion cells and thalamocortical relay neurons in the LGN. To understand how serotonergic inhibition of synaptic transmission influences the transfer of information at this synapse, we examined the EPSCs and firing responses of relay neurons...

Distinct Roles for Spontaneous and Visual Activity in Remodeling of the Retinogeniculate Synapse

Bryan M. Hooks, Chinfei Chen
Neuron,19 October 2006, Volume 52, Issue 2, 281-291

Sensory experience and spontaneous activity play important roles in development of sensory circuits; however, their relative contributions are unclear. Here, we test the role of different forms of activity on remodeling of the mouse retinogeniculate synapse. We found that the bulk of maturation occurs without patterned sensory activity over 4 days spanning eye opening. During this early developmental period, blockade of spontaneous retinal activity by tetrodotoxin, but not visual deprivation, retarded synaptic strengthening and inhibited pruning of excess retinal afferents...

Critical Periods in the Visual System: Changing Views for a Model of Experience-Dependent Plasticity

Bryan M. Hooks, Chinfei Chen
Neuron, 25 October 2007, Volume 56, Issue 2, 312-326

Visual system circuitry, a canonical model system for the study of experience-dependent development, matures before and following the onset of vision. Sensory experience or deprivation during an early critical period results in substantial plasticity and is a crucial factor in establishing the mature circuitry. In adulthood, plasticity has been thought to be reduced or absent. However, recent studies point to the potential for change in neuronal circuits within the mature brain...

Vision Triggers an Experience-Dependent Sensitive Period at the Retinogeniculate Synapse

Bryan M. Hooks and Chinfei Chen
The Journal of Neuroscience, 30 April 2008, Volume 28, Issue 18, 4807-4817

In the mammalian visual system, sensory experience is widely thought to sculpt cortical circuits during a precise critical period. In contrast, subcortical regions, such as the thalamus, were thought to develop at earlier ages in a vision-independent manner. Recent studies at the retinogeniculate synapse, however, have demonstrated an influence of vision on the formation of synaptic circuits in the thalamus. In mice, dark rearing from birth does not alter normal developmental maturation of the connection between retina and thalamus. However, deprivation 20 d after birth [postnatal day 20 (p20)] resulted in dramatic weakening...

Experience-Dependent Retinogeniculate Synapse Remodeling Is Abnormal in MeCP2-Deficient Mice

Joao Noutel, Y. Kate Hong, Byunghee Leu, Erin Kang, Chinfei Chen
Neuron, 14 April 2011, Volume 70, Issue 1, 35-42

Mutations in MECP2 underlie the neurodevelopmental disorder Rett (RTT) syndrome. One hallmark of RTT is relatively normal development followed by a later onset of symptoms. Growing evidence suggests an etiology of disrupted synaptic function, yet it is unclear how these abnormalities explain the clinical presentation of RTT. Here we investigate synapse maturation in Mecp2-deficient mice at a circuit with distinct developmental phases– the retinogeniculate synapse. We find that synapse development in mutants is comparable to that of WT littermates between postnatal days 9–21, indicating that initial phases of synapse formation...

Wiring and rewiring of the retinogeniculate synapse

Hong YK, Chen C
Current Opinion in Neurobiology, 21 April 2011, Volume 21, Issue 2, 228-37

The formation and refinement of synaptic circuits are areas of research that have fascinated neurobiologists for decades. A recurrent theme seen at many CNS synapses is that neuronal connections are at first imprecise, but refine and can be rearranged with time or with experience. Today, with the advent of new technologies to map and monitor neuronal circuits, it is worthwhile to revisit a powerful experimental model for examining the development and plasticity of synaptic circuits-the retinogeniculate synapse...

Presynaptic Modulation of the Retinogeniculate Synapse

Chinfei Chen, Wade G. Regehr
The Journal of Neuroscience, 15 April 2003, Volume 23, Issue 8, 3130-3135

Modulatory projections from brainstem nuclei and intrinsic thalamic interneurons play a significant role in modifying sensory information as it is relayed from the thalamus to the cortex. In the lateral geniculate nucleus (LGN), neurotransmitters released from these modulatory inputs can affect the intrinsic conductances of thalamocortical relay neurons, thus altering their firing properties. Here, we show that in addition to postsynaptic effects, neuromodulators such as serotonin (5-HT) and GABA can act presynaptically to regulate neurotransmitter release at the synapse between retinal ganglion cells (RGCs) and relay neurons in the LGN, the retinogeniculate synapse...

Contributions of Receptor Desensitization and Saturation to Plasticity at the Retinogeniculate Synapse

Chinfei Chen, Dawn M. Blitz, Wade G. Regehr
Neuron, 28 February 2002, Volume 33, Issue 5, 779-788

The retinogeniculate synapse conveys visual information from the retina to thalamic relay neurons. Here, we examine the mechanisms of short-term plasticity that can influence transmission at this connection in mouse brain slices. Our studies show that synaptic strength is modified by physiological activity patterns due to marked depression at high frequencies. Postsynaptic mechanisms of plasticity make prominent contributions to this synaptic depression...

Developmental Remodeling of the Retinogeniculate Synapse

Chinfei Chen, Wade G. Regehr
Neuron, December 2000,Volume 28, Issue 3, 955-966

Anatomical rearrangement of retinogeniculate connections contributes to the refinement of synaptic circuits in the developing visual system, but the underlying changes in synaptic function are unclear. Here, we study such changes in mouse brain slices. Each geniculate cell receives a surprisingly large number of retinal inputs (>20) well after eye-specific zones are formed. All but one to three of these inputs are eliminated over a 3-week period spanning eye opening...

©2018 BY CHINFEI CHEN LAB