Functional Diversity of Thalamic Reticular Subnetworks

Abstract

The activity of the GABAergic neurons of the thalamic reticular nucleus (TRN) has long been known to play important roles in modulating the flow of information through the thalamus and in generating changes in thalamic activity during transitions from wakefulness to sleep. Recently, technological advances have considerably expanded our understanding of the functional organization of TRN. These have identified an impressive array of functionally distinct subnetworks in TRN that participate in sensory, motor, and/or cognitive processes through their different functional connections with thalamic projection neurons. Accordingly, “first order” projection neurons receive “driver” inputs from subcortical sources and are usually connected to a densely distributed TRN subnetwork composed of multiple elongated neural clusters that are topographically organized and incorporate spatially corresponding electrically connected neurons—first order projection neurons are also connected to TRN subnetworks exhibiting different state-dependent activity profiles. “Higher order” projection neurons receive driver inputs from cortical layer 5 and are mainly connected to a densely distributed TRN subnetwork composed of multiple broad neural clusters that are non-topographically organized and incorporate spatially corresponding electrically connected neurons. And projection neurons receiving “driver-like” inputs from the superior colliculus or basal ganglia are connected to TRN subnetworks composed of either elongated or broad neural clusters. Furthermore, TRN subnetworks that mediate interactions among neurons within groups of thalamic nuclei are connected to all three types of thalamic projection neurons. In addition, several TRN subnetworks mediate various bottom-up, top-down, and internuclear attentional processes: some bottom-up and top-down attentional mechanisms are specifically related to first order projection neurons whereas internuclear attentional mechanisms engage all three types of projection neurons. The TRN subnetworks formed by elongated and broad neural clusters may act as templates to guide the operations of the TRN subnetworks related to attentional processes. In this review article, the evidence revealing the functional TRN subnetworks will be evaluated and will be discussed in relation to the functions of the various sensory and motor thalamic nuclei with which these subnetworks are connected.

Two dynamically distinct circuits driving inhibition in sensory thalamus

“…We first explored the cellular composition of the TRN, characterizing expression of parvalbumin (PV), calbindin (CB), and somatostatin (SOM)-three markers previously found to be useful in differentiating functionally distinct neural types in the neocortex and elsewhere 13 . Brain sections spanning the somatosensory sector of the TRN 4,7,8 were prepared from SOM-Cre mice that had been crossed with a Cre-dependent tdTomato (tdT) reporter, then stained immunohistochemically for CB and PV (Fig. 1a).…”

“…First-order VP and higher-order POM thalamocortical (TC) nuclei transmit distinct information to different targets in the neocortex and send collaterals to the TRN, the latter leading to both openand closed-loop thalamic inhibition [4][5][6]8 . Clarifying the organization of these circuits, including how first-order and higher-order TC nuclei synapse with specific subsets of TRN neurons 16 , is essential to understanding thalamic information processing 7 .…”

“…There was greater short-term depression for the central cells than the edge cells (p < 0.03, ANOVA, stim. [2][3][4][5][6][7][8][9][10]. Depression in the two edge cell groups did not differ (Bonferroni's t-test, all p>0.99).…”

A thalamic reticular circuit for head direction cell tuning and spatial navigation

“…However, in the interest of survival, environmental cues may need to be detected rapidly to adapt 31 navigational strategies without potentially time-consuming cortical elaboration. A major site for 32 subcortical gating of sensory stimuli is the inhibitory thalamic reticular nucleus (TRN) that shows 33 a unique anatomical positioning at the interface between sensory thalamic nuclei and cortex 34 (Scheibel and Scheibel, 1966;Pinault, 2004;Crabtree, 2018). The significance of TRN in 35 controlling sensory flow is now documented for the gain control of incoming sensory inputs (Le 36 Masson et al, 2002), the sharpening of receptive fields (Lee et al, 1994; Soto-Sánchez et al, 37 2017), attentional modulation of monomodal (Halassa et al, 2014) or multimodal conflicting 38 sensory inputs (Ahrens et al, 2015;Wimmer et al, 2015), and sensory induced escape (Dong et 39 al., 2019).…”

“…Anatomical and physiological identification of synaptic inputs to TRN has repeatedly opened a 430 novel point of view for the TRN's active role in gating sensory information flow to and from the 431 cortex (for review, see (Crabtree, 2018)). We uncover here a previously undescribed excitatory 432 input to TRN from the parahippocampal dPreS and the RSC that shows high connectivity, 433 mediates robust feedforward inhibition to ATN and shapes HD tuning in AD.…”