Nuclei-specific differences in nerve terminal distribution, morphology, and development in mouse visual thalamus

Abstract

BackgroundMouse 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.ResultsImmunolabeling 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.ConclusionsTaken 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.

Adaptive reorganization of retinogeniculate axon terminals in dorsal lateral geniculate nucleus following experimental mild traumatic brain injury

“…Examination of VGLUT2 immunoreactivity within dLGN allowed for identification of the retinogeniculate axon terminals downstream of the injured optic nerve. Assessment of this immunoreactivity in our sham-injured animals was consistent with previous reports of normal VGLUT2 immunoreactivity by others (El-Danaf et al, 2015; Hammer et al, 2015, 2014). Within sham animals, the distribution of VGLUT2 immunoreactivity occurred in large clusters of variable size, likely composed of multiple axon terminals as they synapse on proximal dendrites of relay neurons.…”

“…Within sham animals, the distribution of VGLUT2 immunoreactivity occurred in large clusters of variable size, likely composed of multiple axon terminals as they synapse on proximal dendrites of relay neurons. These axon terminal clusters appeared evenly distributed throughout dLGN, a finding consistent with reports on the normal ultrastructure of retinogeniculate synapses upon relay neurons within dLGN (Bickford et al, 2015, 2010; Guido, 2008; Hammer et al, 2015, 2014; Morgan et al, 2016). Comparison of VGLUT2 immunoreactivity in mTBI animals 4 days post-injury to sham demonstrated the persistence of clusters (Figure 1B & D), however, the clusters in dLGN were more widely separated from each other, suggestive of axon terminal loss.…”

LRRTM1 underlies synaptic convergence in visual thalamus

“…Complex RG synapses have been reported in both rodents and higher mammals (Lund and Cunningham, 1972, Jones and Powell, 1969, So et al, 1985, Campbell and Frost, 1987, Guillery and Scott, 1971, Wilson et al, 1984. Similar to the more classical simple RG synapses (which contain a single retinal terminal on a given portion of a relay cell dendrite), these complex RG synapses are absent from other retinorecipient regions of brain (Hammer et al, 2014) ( Figure S1). Since branches of dLGN-projecting RGCs also innervate other retinorecipient nuclei (Dhande et al, 2015), we interpret this to suggest that targetderived signals must be generated in dLGN to pattern the unique transformation of retinal axons into simple and complex RG synapses.…”

“…In addition to being segregated based on class, retinal projections in dLGN are unique in that they form structurally and functionally distinct synapses compared to their counterparts in other retinorecipient nuclei (Hammer et al, 2014). Retinal terminals in dLGN are prototypic "driver" inputs which are dramatically large (compared to adjacent non-retinal inputs) and are capable of generating strong excitatory postsynaptic responses in thalamic relay cells.…”

Toxoplasmainduces stripping of perisomatic inhibitory synapses

“…Serial block face scanning electron microscopy. SBFSEM was performed as described previously (Hammer et al 2014;Monavarfeshani et al 2018). Briefly, mice were perfused with 0.1M sodium cacodylate buffer containing 4% PFA and 2.5% glutaraldehyde and immediately 300 µm vibratomed coronal sections were collected.…”