Region Selective Cortical Control Of The Thalamic Reticular Nucleus

Abstract

Corticothalamic pathways, responsible for the top-down control of the thalamus display a classical, canonical organization in that every cortical region sends dual, layer 6 (L6) and layer 5 (L5) output to the thalamus. Here we demonstrate a qualitative, region-specific difference in the organization of corticothalamic pathways. We show that L5 pyramidal cells of the frontal, but not other cortical regions establish monosynaptic connection with the inhibitory thalamic reticular nucleus (TRN). The frontal L5-TRN pathway paralleled the L6-TRN projection but displayed distinct morphological and physiological features. The exact spike output of the L5 contacted TRN cells correlated with the level of cortical synchrony. Optogenetic perturbation of the L5-TRN connection disrupted the tight link between cortical and TRN activity. L5-driven TRN cells innervated all thalamic nuclei involved in the control of frontal cortical activity. Our data show that frontal cortical functions require a highly specialized cortical control over intrathalamic inhibitory processes.

Micropopulation mapping of the mouse parafascicular nucleus connections reveals diverse input–output motifs

“…Intriguingly, despite the caudal location of Pf within the thalamus, the TRN neurons that innervate it are located in a rostral and ventral part of TRN. The same TRN zone has been reported to project back to Pf in rats (Kolmac and Mitrofanis, 1997) and to be selectively targeted by the axons from other motor thalamic nuclei, as well as by corticothalamic axons from the motor cortex (Hádinger et al, 2023).…”

Sleep spindles in primates: modelling the effects of distinct laminar thalamocortical connectivity in core, matrix, and reticular thalamic circuits

“…Projections from L5 to TRN have only recently been shown directly or indirectly for some cortical areas and at variable levels (Hádinger et al, 2022; Prasad et al, 2020; Zikopoulos and Barbas, 2007b, 2006). In primates, several thalamic nuclei, especially those connected with prefrontal cortices, receive anywhere from 20-50% of their cortical projections from layer 5 pyramidal neurons (Xiao et al, 2009).…”

“…The TRN is a key generator of spindle oscillations that intercepts all TC communications but sends inhibitory projections only back to the thalamus (Luthi, 2014;Steriade, 2005;Steriade et al, 1987). The TRN gets most of its cortical input from L6 pyramidal neurons that participate in core TC loops Bourassa and Desche nes, 1995;Kakei et al, 2001), but is predicted to get substantial input from L5 pyramidal neurons of matrix TC loops in primates Barbas, 2007b, 2006), as was recently shown to some extent in mice (Hádinger et al, 2022;Hadinger et al, 2019;Prasad et al, 2020).…”

“…1) and overall, they were larger than terminals from sensory association areas known to originate from layer 6. Recent studies in mice confirmed that there are direct projections of variable density from L5 pyramidal neurons to TRN from some cortical areas, especially association areas that likely participate in matrix circuits (Hádinger et al, 2022;Hadinger et al, 2019;Prasad et al, 2020). Since the presence of L5 projections to TRN is not ubiquitous we represent it with a dotted line from L5 to TRN in the simplified diagram in Fig.…”

Predicting distributed working memory activity in a large-scale mouse brain: the importance of the cell type-specific connectome

“…There are no recurrent connections in the thalamus within or across thalamic nuclei (Jones 2007). The effect of thalamic reticular nucleus neurons was included indirectly as a constant inhibitory current to all thalamic areas (Crabtree 2018;Hádinger et al 2023). Similarly to cortical areas, the thalamus is organized along a measured hierarchy (Harris et al 2019).…”