Cortico-Thalamo-Cortical Circuits of Mouse Forelimb S1 Are Organized Primarily as Recurrent Loops

Abstract

Cortical projections to the thalamus arise from corticothalamic (CT) neurons in layer 6 and pyramidal tract-type (PT) neurons in layer 5B. We dissected the excitatory synaptic connections in the somatosensory thalamus formed by CT and PT neurons of the primary somatosensory (S1) cortex, focusing on mouse forelimb S1. Mice of both sexes were studied. The CT neurons in S1 synaptically excited S1projecting thalamocortical (TC) neurons in subregions of both the ventral posterior lateral and posterior (PO) nuclei, forming a pair of recurrent cortico-thalamo-cortical (C-T-C) loops. The PT neurons in S1 also formed a recurrent loop with S1-projecting TC neurons in the same subregion of the PO. The PT neurons in the adjacent primary motor (M1) cortex formed a separate recurrent loop with M1projecting TC neurons in a nearby subregion of the PO. Collectively, our results reveal that C-T-C circuits of mouse forelimb S1 are primarily organized as multiple cortical cell-type-specific and thalamic subnucleus-specific recurrent loops, with both CT and PT neurons providing the strongest excitatory input to TC neurons that project back to S1. The findings, together with those of related studies of C-T-C circuits, thus suggest that recurrently projecting thalamocortical neurons are the principal targets of cortical excitatory input to the mouse somatosensory and motor thalamus.

Visual intracortical and transthalamic pathways carry distinct information to cortical areas

“…It is therefore still unresolved if they are part of transthalamic, feedforward pathways between cortical areas. Alternatively, pulvinar circuits could provide additional visual pathways from the retina to the cortex via the superior colliculus or form specific, reciprocal loops with individual cortical areas (Wurtz et al, 2011;Guo Z. et al, 2017;Beltramo and Scanziani, 2019;Bennett et al, 2019;Guo K. et al, 2020). Furthermore, it is unclear what information these pathways through the pulvinar bring to cortical visual areas, and how the signals they convey differ from those carried by direct intracortical projections.…”

Circuit organization of the excitatory sensorimotor loop through hand/forelimb S1 and M1

“…Thus, for the hand-related 381 pathways, and in contrast to cuneo-PO projections described in other species such as the cat 382 (Berkley et al, 1986;Loutit et al, 2020), we did not identify a clear cuneo-PO counterpart to the 383 trigemino-PO circuit in the whisker-related paralemniscal pathway. Although ascending 384 subcortical sources of input to hand-related PO neurons in the mouse remain to be identified, 385 descending cortical axons from hand S1 target a subregion of PO, strongly exciting recurrently 386 projecting PO neurons there to form cortico-thalamo-cortical loops (Guo et al, 2020). 387…”

“…Somatosensory mapping. Transcranial fluorescence imaging of somatosensory responses was performed as described previously (Guo et al 2020), with several modifications. Briefly, after undergoing head-post mounting surgery, mice were injected with ketamine (80-100 mg/kg) and…”

A subpopulation of L6b neurons provides driver‐like input to the posteromedial thalamus

“…In contrast, Drd1a CT neurons receive little thalamic input and are predominantly driven by long-range cortical projections from areas such as primary motor cortex (M1) and secondary somatosensory cortex (S2) (Zolnik et al 2020). Lack of thalamic input to a subpopulation of L6b neurons is unexpected as L6 is traditionally thought of as a main component of recurrent corticothalamocortical (CTC) loops, where CT neurons in L6 project to thalamus and specifically target neurons that project back to the same cortical area (Guo et al 2020). In this sense, they are considered to be closed loops, as opposed to open loops which form transthalamic connections to other cortical areas (Sherman, 2016;Guo et al 2020).…”

“…Lack of thalamic input to a subpopulation of L6b neurons is unexpected as L6 is traditionally thought of as a main component of recurrent corticothalamocortical (CTC) loops, where CT neurons in L6 project to thalamus and specifically target neurons that project back to the same cortical area (Guo et al 2020). In this sense, they are considered to be closed loops, as opposed to open loops which form transthalamic connections to other cortical areas (Sherman, 2016;Guo et al 2020). Closed loops are thought to allow the dynamic modulation of sensory responses in both thalamus and cortex through the recruitment of inhibitory interneurons in TRN (Kirchgessner et al 2020) (Fig.…”