Modality-specific thalamocortical inputs instruct the identity of postsynaptic L4 neurons

Abstract

During development, thalamocortical (TC) input has a critical role in the spatial delineation and patterning of cortical areas, yet the underlying cellular and molecular mechanisms that drive cortical neuron differentiation are poorly understood. In the primary (S1) and secondary (S2) somatosensory cortex, layer 4 (L4) neurons receive mutually exclusive input originating from two thalamic nuclei: the ventrobasalis (VB), which conveys tactile input, and the posterior nucleus (Po), which conveys modulatory and nociceptive input. Recently, we have shown that L4 neuron identity is not fully committed postnatally, implying a capacity for TC input to influence differentiation during cortical circuit assembly. Here we investigate whether the cell-type-specific molecular and functional identity of L4 neurons is instructed by the origin of their TC input. Genetic ablation of the VB at birth resulted in an anatomical and functional rewiring of Po projections onto L4 neurons in S1. This induced acquisition of Po input led to a respecification of postsynaptic L4 neurons, which developed functional molecular features of Po-target neurons while repressing VB-target traits. Respecified L4 neurons were able to respond both to touch and to noxious stimuli, in sharp contrast to the normal segregation of these sensory modalities in distinct cortical circuits. These findings reveal a behaviourally relevant TC-input-type-specific control over the molecular and functional differentiation of postsynaptic L4 neurons and cognate intracortical circuits, which instructs the development of modality-specific neuronal and circuit properties during corticogenesis.

Reciprocal Interareal Connections to Corticospinal Neurons in Mouse M1 and S2

“…Both areas receive corticocortical projections from S1 (see Introduction) and thalamocortical projections from the posterior (PO) nucleus of the thalamus (Herkenham, 1980;Burton, 1986;Theyel et al, 2010;Pouchelon et al, 2014). However, the circuits of M1 and S2, although similar, are also differentiated in several ways.…”

Fate and freedom in developing neocortical circuits

“…Interestingly, in the case of the somatosensory cortex, deprived S1 circuits acquire S2-like features (that is, an increase in excitatory/inhibitory ratio), suggesting that thalamic input not only affects L4 neurons but also determines downstream circuit assembly79. These findings suggest that associative cortical identity is a ground-state feature, and that acquisition of primary cortical area circuit properties is imparted by first-order thalamic input.…”

“…These studies have shown that synaptic release of glutamate from the thalamocortical axons is required for the assembly of L4 neurons into barrels and dendritic polarization towards these axons, in particular via activation of NMDA receptors and metabotropic glutamate receptors17. In addition, several transcription factors, including Lhx2, Npas4, Zbtb20 function to polarize L4 dendrites towards incoming VB axons in S1 (refs 79, 80, 81), and Btbd3 has a similar role in V1 (ref. 82).…”

“…In the absence of exteroceptive, first-order thalamic input, primary areas (S1, V1) acquire molecular properties of associative cortical areas, such as S2 and V2 (refs 79, 83, 84). Interestingly, in the case of the somatosensory cortex, deprived S1 circuits acquire S2-like features (that is, an increase in excitatory/inhibitory ratio), suggesting that thalamic input not only affects L4 neurons but also determines downstream circuit assembly79.…”

Quand la migration de neurones signalisateurs contrôle la régionalisation du cortex cérébral

“…Récem-ment, un rôle des entrées sensorielles en provenance du thalamus (projections thalamo-corticales 2 ) a pu être mis en évidence à des stades post-nataux. Il a ainsi été proposé que ces projections thalamo-corticales déterminent la distinction entre aires primaires et secondaires dans le cortex visuel et somatosensoriel 3 [1,2] [3]. Cependant, l'implication exclusive de signaux diffu-2 Le thalamus est une structure sous-corticale composée d'un ensemble de noyaux, certains d'entre eux recevant l'information provenant des récepteurs de différentes modalités sensorielles et projetant directement vers les aires corticales primaires.…”