Browsing by Author "Govindaiah, Gubbi"

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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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    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.