Distinct subnetworks of the thalamic reticular nucleus

Abstract

The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, is known to regulate thalamocortical interactions critical for sensory processing, attention and cognition 1 - 5 . TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders 6 - 9 . Currently, little is known about the organizational principles underlying its divergent functions. We performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that TRN cellular heterogeneity is characterized by a transcriptomic gradient of two negatively correlated gene expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core/shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections to the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN-thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. Taken together, our study provides a comprehensive atlas for TRN neurons at the single-cell resolution, and links molecularly defined subnetworks to the functional organization of the thalamo-cortical circuits.

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.…”

“…Confocal microscopy revealed dense axonal 4 boutons from SST nRT neurons in the dLGN, but only very sparse input from PV nRT neurons (Figure 1B-D). This was surprising given that PV neurons are thought to represent the major cellular population of nRT (Clemente-Perez et al, 2017;Li et al, 2020). As previously shown, PV but not SST neurons from the nRT projected densely to the somatosensory ventroposteromedial (VPM) thalamocortical nucleus (Figure 1B-D, Figure 1-figure supplement 2).…”

“…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.…”

Stable thalamocortical learning between medial-dorsal thalamus and cortical attractor networks captures cognitive flexibility

“…We can apply our method to animal model of schizophrenia and see whether we can understand the reason for loss of performance when an animal model of schizophrenia is engaged in various tasks [55]. Generally, it is claimed that the way schizophrenia animal got malfunction is due to the reduction in strength of the thalamo-cortical connectivity [56,57]. Our simulation result is supporting this statement.…”

Involvement of the thalamic reticular nucleus in prepulse inhibition of acoustic startle

“…In their study, the PTCHD1 knockout mice showed reduced repetitive bursting of TRN neurons, but no change in PPI performance 12 . In consideration of our findings, different kinds of burst firing modes, like single burst firing or repetitive burst firing, may modulate sensory processing in different ways 2 , 37 . Undoubtedly, complete blockage of burst firing can impair PPI performance.…”