Two dynamically distinct circuits driving inhibition in sensory thalamus

Abstract

Most sensory information destined for the neocortex is relayed there from the thalamus, where considerable transformation occurs 1,2 . One powerful means of transformation involves interactions between excitatory thalamocortical neurons that carry data to cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate flow of those data 3-6 . Despite enduring recognition of the TRN's importance 7-9 , understanding of its cell types, their organization, and their functional properties has lagged that of the thalamocortical systems it controls.Here we address this, investigating somatosensory and visual circuits of the TRN. First, in the somatosensory TRN we observed two groups of genetically defined neurons that are topographically segregated, physiologically distinct, and connect reciprocally with independent thalamocortical nuclei via dynamically divergent synapses. Calbindin-expressing cells, located in the central core, connect with the ventral posterior nucleus (VP), the primary somatosensory thalamocortical relay. In contrast, somatostatin-expressing cells, residing along the surrounding edges of TRN, synapse with the posterior medial thalamic nucleus (POM), a higher-order structure that carries both top-down and bottom-up information 10-12 . The two TRN cell groups process their inputs in pathway-specific ways. Synapses from VP to central TRN cells evoke rapid currents that depress deeply during repetitive activity, driving phasic spike output. In contrast, synapses from POM to edge TRN cells evoke slower, sustained currents that drive more persistent spiking. Differences in intrinsic physiology of TRN cell types, including state-dependent bursting, also contribute to these output dynamics. Thus, processing specializations of the two TRN circuits appear to be tuned to the types of signals they carry-the primary central circuit to discrete sensory events, and the higher-order edge circuit to temporally distributed signals integrated from multiple sources. Central and edge circuits of the visual TRN and their associated thalamocortical nuclei closely resemble those of the somatosensory circuits. These results provide fundamental insights about how subnetworks of TRN neurons could differentially process distinct classes of thalamic information.

Gamma rhythms and visual information in mouse V1 specifically modulated by somatostatin+ neurons in reticular thalamus

“…Using immunohistochemistry and confocal imaging, we confirmed that putative synaptic boutons from PV and SST nRT neurons are largely distinct (Figure 1-figure supplement 2), although certain neurons do express both markers (Figure 1-figure supplement 2) consistent with previous work (Clemente-Perez et al, 2017). Calbindin has been suggested as another marker of a subpopulation of nRT neurons (Martinez-Garcia et al, 2020); however, this has not been confirmed by single-nuclear RNA sequencing studies, which found no absolutely exclusive genetic markers between nRT cell types, although gradients in Spp1 and Ecl1 gene expression were noted between core and shell parts of the nRT (Li et al, 2020). Future studies at multiple levels of analysis (protein, genetic) will determine whether the differences between results of the studies cited above are due to use of different transgenic mouse models.…”

“…The existence of functionally distinct neuron types within the nRT has been shown (Lee et al, 2007;Halassa et al, 2014), and has recently been associated with PV and SST markers (Clemente-Perez et al, 2017), and further extended to additional molecular markers (Li et al, 2020;Martinez-Garcia et al, 2020). Finding molecular markers of functionally distinct nRT cells may be significant because it could allow us to selectively perturb distinct functions of the nRT.…”

Higher-order thalamic nuclei facilitate the generalization and maintenance of spike-and-wave discharges of absence seizures

“…Notably, the zona incerta has reciprocal connections with the initiation site and when inhibited, reduces SWD occurrence (Liang et al, 2011;Shaw et al, 2013). Although S1 has been shown to affect VB neurons via the NRT during SWD (McCafferty et al, 2018) this cannot be generalized to the PO since NRT microcircuits between FO and HO differ in their location and properties (Martinez-Garcia et al, 2020).…”

Region Selective Cortical Control Of The Thalamic Reticular Nucleus

“…These neurons had also significantly lower firing and burst rates and were spatially mixed with the neurons which showed significant correlation with the cortical LFP (FigS4). Recent investigations (Clemente-Perez et al, 2017; Li et al, 2020; Martinez-Garcia et al, 2020) demonstrated the presence of at least two morphologically and physiologically different cell types in the TRN. Whether the two anterior TRN populations in our experiments corresponds with these previously described groups requires further investigation.…”