Browsing by Author "Guido, William"

Now showing 1 - 7 of 7
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    Developmental remodeling of relay cells in the dorsal lateral geniculate nucleus in the absence of retinal input
    El-Danaf, Rana N.; Krahe, Thomas E.; Dilger, Emily K.; Bickford, Martha E.; Fox, Michael A.; Guido, William (BMC, 2015)
    Background: The dorsal lateral geniculate nucleus (dLGN) of the mouse has been an important experimental model for understanding thalamic circuit development. The developmental remodeling of retinal projections has been the primary focus, however much less is known about the maturation of their synaptic targets, the relay cells of the dLGN. Here we examined the growth and maturation of relay cells during the first few weeks of life and addressed whether early retinal innervation affects their development. To accomplish this we utilized the math5 null (math5−/−) mouse, a mutant lacking retinal ganglion cells and central projections. Results: The absence of retinogeniculate axon innervation led to an overall shrinkage of dLGN and disrupted the pattern of dendritic growth among developing relay cells. 3-D reconstructions of biocytin filled neurons from math5−/− mice showed that in the absence of retinal input relay cells undergo a period of exuberant dendritic growth and branching, followed by branch elimination and an overall attenuation in dendritic field size. However, math5−/− relay cells retained a sufficient degree of complexity and class specificity, as well as their basic membrane properties and spike firing characteristics. Conclusions: Retinal innervation plays an important trophic role in dLGN development. Additional support perhaps arising from non-retinal innervation and signaling is likely to contribute to the stabilization of their dendritic form and function.
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    Diverse GABAergic neurons organize into subtype-specific sublaminae in the ventral lateral geniculate nucleus
    Sabbagh, Ubadah; Govindaiah, Gubbi; Somaiya, Rachana D.; Ha, Ryan V.; Wei, Jessica C.; Guido, William; Fox, Michael A. (Wiley, 2020-05-19)
    In the visual system, retinal axons convey visual information from the outside world to dozens of distinct retinorecipient brain regions and organize that information at several levels, including either at the level of retinal afferents, cytoarchitecture of intrinsic retinorecipient neurons, or a combination of the two. Two major retinorecipient nuclei which are densely innervated by retinal axons are the dorsal lateral geniculate nucleus, which is important for classical image-forming vision, and ventral LGN (vLGN), which is associated with non-image-forming vision. The neurochemistry, cytoarchitecture, and retinothalamic connectivity in vLGN remain unresolved, raising fundamental questions of how it receives and processes visual information. To shed light on these important questions, used in situ hybridization, immunohistochemistry, and genetic reporter lines to identify and characterize novel neuronal cell types in mouse vLGN. Not only were a high percentage of these cells GABAergic, we discovered transcriptomically distinct GABAergic cell types reside in the two major laminae of vLGN, the retinorecipient, external vLGN (vLGNe) and the non-retinorecipient, internal vLGN (vLGNi). Furthermore, within vLGNe, we identified transcriptionally distinct subtypes of GABAergic cells that are distributed into four adjacent sublaminae. Using trans-synaptic viral tracing and in vitro electrophysiology, we found cells in each these vLGNe sublaminae receive monosynaptic inputs from retina. These results not only identify novel subtypes of GABAergic cells in vLGN, they suggest the subtype-specific laminar distribution of retinorecipient cells in vLGNe may be important for receiving, processing, and transmitting light-derived signals in parallel channels of the subcortical visual system.
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    Modulation of CREB in the Dorsal Lateral Geniculate Nucleus of Dark-Reared Mice
    Krahe, Thomas E.; Seabrook, Tania A.; Chen, Ching-Kang; Fox, Michael A.; Guido, William (Hindawi, 2012)
    The cAMP-response element-binding protein (CREB) plays an important role in visual cortical plasticity that follows the disruption of sensory activity, as induced by dark rearing (DR). Recent findings indicate that the dorsal lateral geniculate nucleus (dLGN) of thalamus is also sensitive to altered sensory activity. DR disrupts retinogeniculate synaptic strength and pruning in mice, but only when DR starts one week after eye opening (delayed DR, DDR) and not after chronic DR (CDR) from birth.While DR upregulates CREB in visual cortex, whether it also modulates this pathway in dLGN remains unknown. Here we investigate the role of CREB in the dLGN of mice that were CDR or DDR using western blot and immunofluorescence. Similar to findings in visual cortex, CREB is upregulated in dLGN after CDR and DDR. These findings are consistent with the proposal that DR up-regulates the CREB pathway in response to decreased visual drive.
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    A Molecular Mechanism Regulating the Timing of Corticogeniculate Innervation
    Brooks, Justin M.; Su, Jianmin; Levy, Carl; Wang, Jessica S.; Seabrook, Tania A.; Guido, William (Elsevier, 2013-11-14)
    Neural circuit formation demands precise timing of innervation by different classes of axons. However, the mechanisms underlying such activity remain largely unknown. In the dorsal lateral geniculate nucleus (dLGN), axons from the retina and visual cortex innervate thalamic relay neurons in a highly coordinated manner, with those from the cortex arriving well after those from retina. The differential timing of retino- and corticogeniculate innervation is not a coincidence but is orchestrated by retinal inputs. Here, we identified a chondroitin sulfate proteoglycan (CSPG) that regulates the timing of corticogeniculate innervation. Aggrecan, a repulsive CSPG, is enriched in neonatal dLGN and inhibits cortical axons from prematurely entering the dLGN. Postnatal loss of aggrecan from dLGN coincides with upregulation of aggrecanase expression in the dLGN and corticogeniculate innervation and, it is important to note, is regulated by retinal inputs. Taken together, these studies reveal a molecular mechanism through which one class of axons coordinates the temporal targeting of another class of axons.
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    Nuclei-specific differences in nerve terminal distribution, morphology, and development in mouse visual thalamus
    Hammer, Sarah; Carrillo, Gabriela Lizana; Govindaiah, Gubbi; Monavarfeshani, Aboozar; Bircher, Joseph S.; Su, Jianmin; Guido, William; Fox, Michael A. (BMC, 2014)
    Background: Mouse visual thalamus has emerged as a powerful model for understanding the mechanisms underlying neural circuit formation and function. Three distinct nuclei within mouse thalamus receive retinal input, the dorsal lateral geniculate nucleus (dLGN), the ventral lateral geniculate nucleus (vLGN), and the intergeniculate nucleus (IGL). However, in each of these nuclei, retinal inputs are vastly outnumbered by nonretinal inputs that arise from cortical and subcortical sources. Although retinal and nonretinal terminals associated within dLGN circuitry have been well characterized, we know little about nerve terminal organization, distribution and development in other nuclei of mouse visual thalamus. Results: Immunolabeling specific subsets of synapses with antibodies against vesicle-associated neurotransmitter transporters or neurotransmitter synthesizing enzymes revealed significant differences in the composition, distribution and morphology of nonretinal terminals in dLGN, vLGN and IGL. For example, inhibitory terminals are more densely packed in vLGN, and cortical terminals are more densely distributed in dLGN. Overall, synaptic terminal density appears least dense in IGL. Similar nuclei-specific differences were observed for retinal terminals using immunolabeling, genetic labeling, axonal tracing and serial block face scanning electron microscopy: retinal terminals are smaller, less morphologically complex, and more densely distributed in vLGN than in dLGN. Since glutamatergic terminal size often correlates with synaptic function, we used in vitro whole cell recordings and optic tract stimulation in acutely prepared thalamic slices to reveal that excitatory postsynaptic currents (EPSCs) are considerably smaller in vLGN and show distinct responses following paired stimuli. Finally, anterograde labeling of retinal terminals throughout early postnatal development revealed that anatomical differences in retinal nerve terminal structure are not observable as synapses initially formed, but rather developed as retinogeniculate circuits mature. Conclusions: Taken together, these results reveal nuclei-specific differences in nerve terminal composition, distribution, and morphology in mouse visual thalamus. These results raise intriguing questions about the different functions of these nuclei in processing light-derived information, as well as differences in the mechanisms that underlie their unique, nuclei-specific development.
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    Pattern of Driver-Like Input onto Neurons of the Mouse Ventral Lateral Geniculate Nucleus
    Govindaiah, Gubbi; Fox, Michael A.; Guido, William (Society Neuroscience, 2023-01)
    The ventral lateral geniculate nucleus (vLGN) is a retinorecipient region of thalamus that contributes to a num-ber of complex visual behaviors. Retinal axons that target vLGN terminate exclusively in the external subdivi-sion (vLGNe), which is also transcriptionally and cytoarchitectonically distinct from the internal subdivision (vLGNi). While recent studies shed light on the cell types and efferent projections of vLGNe and vLGNi, we have a crude understanding of the source and nature of the excitatory inputs driving postsynaptic activity in these regions. Here, we address this by conducting in vitro whole-cell recordings in acutely prepared thalamic slices and using electrical and optical stimulation techniques to examine the postsynaptic excitatory activity evoked by the activation of retinal or cortical layer V input onto neurons in vLGNe and vLGNi. Activation of ret-inal afferents by electrical stimulation of optic tract or optical stimulation of retinal terminals resulted in robust driver-like excitatory activity in vLGNe. Optical activation of corticothalamic terminals from layer V resulted in similar driver-like activity in both vLGNe and vLGNi. Using a dual-color optogenetic approach, we found that many vLGNe neurons received convergent input from these two sources. Both individual pathways displayed similar driver-like properties, with corticothalamic stimulation leading to a stronger form of synaptic depression than retinogeniculate stimulation. We found no evidence of convergence in vLGNi, with neurons only respond-ing to corticothalamic stimulation. These data provide insight into the influence of excitatory inputs to vLGN and reveal that only neurons in vLGNe receive convergent input from both sources.Significance StatementThe ventral lateral geniculate nucleus is traditionally thought of as a thalamic visual recipient structure. However, recent studies reveal its divergent output to a variety of nonvisual subcortical structures helps control an array of light-mediated defensive and mood-related behaviors. Despite this knowledge, we still lack an understanding of where and how inputs to this nucleus drive activity. Here we show that vLGN re-ceives strong, driver-like excitatory input from two sources: the retina and cortical layer V. The external sub-division receives convergent input from both sources, whereas the internal division receives input only from layer V. Such an arrangement has important implications for understanding the functional organization of vLGN and its role in integrating vision with internal behavioral states.
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    Retinal inputs signal astrocytes to recruit interneurons into visual thalamus
    Su, Jianmin; Charalambakis, Naomi E.; Sabbagh, Ubadah; Somaiya, Rachana D.; Monavarfeshani, Aboozar; Guido, William; Fox, Michael A. (2020-02-04)
    Inhibitory interneurons comprise a fraction of the total neurons in the visual thalamus but are essential for sharpening receptive field properties and improving contrast-gain of retinogeniculate transmission. During early development, these interneurons undergo long-range migration from germinal zones, a process regulated by the innervation of the visual thalamus by retinal ganglion cells. Here, using transcriptomic approaches, we identified a motogenic cue, fibroblast growth factor 15 (FGF15), whose expression in the visual thalamus is regulated by retinal input. Targeted deletion of functional FGF15 in mice led to a reduction in thalamic GABAergic interneurons similar to that observed in the absence of retinal input. This loss may be attributed, at least in part, to misrouting of interneurons into nonvisual thalamic nuclei. Unexpectedly, expression analysis revealed that FGF15 is generated by thalamic astrocytes and not retino-recipient neurons. Thus, these data show that retinal inputs signal through astrocytes to direct the long-range recruitment of interneurons into the visual thalamus.