A combinatorial input landscape in the “higher-order relay” posterior thalamic nucleus

Abstract

A large part of the thalamus is not directly involved in relaying ascending sensory inputs to the cerebral cortex. The functions and wiring of such "non-primary" nuclei remain unclear. The Posterior nucleus, a representative "non-primary" nucleus of the rodent thalamus, receives heavy and powerful inputs from cortical layer 5 (L5) cells. In addition, Po receives also some trigeminal, spinal and superior colliculus (SC) inputs, as well as powerful inhibitory inputs from the zona incerta (ZI) and anterior pretectal nucleus (APT). To elucidate to which extent these input systems converge or remain separate within Po, we first mapped the distribution of terminals immunolabeled for markers of glutamatergic or GABAergic neurotransmission and L5 terminals constitutively labeled in Rbp4-Cre;Ai14 mice. Besides, we retrogradely traced and quantified the sources of brain and spinal cord input reaching different Po regions. In addition, we compared bouton sizes in axons anterogradely labeled from the above input sources. Our data delineate several domains within Po, each dominated by specific sets of inputs. Cortical L5 afferents predominate in central and ventral Po. In contrast, large glutamatergic terminals from the trigeminal complex and spinal cord as well as GABAergic terminals from APT and ZI prevail in rostral and dorsal Po, and along the border with the ventral posteromedial nucleus. SC inputs preferentially target dorsal and caudal Po. These findings reveal multiple partly overlapping domains within Po. Hence, thalamic neuron subpopulations in different parts of Po may integrate diverse combinations of tactile, motor and pain-related inputs and give rise to functionally diverse thalamocortical subnetworks. Significance statementMany nuclei of the thalamus are not involved in relaying to cortex new information about the world or the body. The functions and wiring of such "non-primary" nuclei remain unclear. Here, we first mapped across the brain and spinal cord the origin of the input pathways reaching the Posterior nucleus, a typical non-primary relay nucleus.Then, we analyzed input distribution within the nucleus and, as a proxy for synaptic strength, the size of their axon terminals. We report a complex tridimensional mosaic of partly overlapping input-specific domains and significant bouton size differences. This wiring may allow diverse inputs to converge in graded combinatorial fashion onto thalamic cell subpopulations, hence giving rise to emergent computations and functionally diverse thalamocortical subnetworks.

Pattern of Driver-Like Input onto Neurons of the Mouse Ventral Lateral Geniculate Nucleus

“…Several laboratories make use of the Rpb4-Cre line to visualize or interrogate layer V corticothalamic projections, especially when done in conjunction with a Cre-dependent viral injection approach ( Grant et al, 2016 ; Hoerder-Suabedissen et al, 2019 ; Prasad et al, 2020 ; Hayashi et al, 2021 ; Carroll et al, 2022 ; Casas-Torremocha et al, 2022 ). While the latter is ideal for achieving cell type specificity, it falls short in providing widespread and sufficient expression in a target structure, a task more readily achieved by using Cre-driver lines.…”

Role of Posterior Medial Thalamus in the Modulation of Striatal Circuitry and Choice Behavior

“…22,23,24,25,26, 34,50,51 Its widespread connectivity with sensory and motor cortical areas (S1, S2, and M1), 2,48,49,54,55,128,129 along with its strong modulation of behavioral state and arousal, 17,18 suggests a significant role in sensory-guided behaviors. While POm-striatal projections are anatomically prominent and robustly overlap with corticostriatal inputs from S1 and M1, 2,29,31,32,33,49,73,130 their functional innervation pattern and potential role in learned behaviors are unknown. Therefore, we aimed to elucidate the functional innervation pattern of POm onto striatal cell types, and the role of POm-striatal projections on behavioral performance and learning.…”

A mechanism for deviance detection and contextual routing in the thalamus: a review and theoretical proposal

“…We do not know if these different L6 inputs converge on individual cells or form parallel processing streams on different TC cells. HO TC and TRN cells also receive multiple drivers from different hierarchical levels, and these drivers do converge in TC cells, which therefore can integrate information across hierarchical levels ( Groh et al, 2014 ; Sampathkumar et al, 2021 ; Carroll et al, 2022 ; Casas-Torremocha et al, 2022 ). Likewise, projections from one sector of the TRN can diverge to multiple nuclei of the dorsal thalamus ( Clemente-Perez et al, 2017 ; Crabtree, 2018 ; Li et al, 2020 ), and modulations of subthreshold membrane potential between TRN sensory modalities have been demonstrated ( Kimura, 2014 ).…”