Developmental interactions between thalamus and cortex: a true love reciprocal story

Abstract

The developmental programs that control the specification of cortical and thalamic territories are maintained largely as independent processes. However, bulk of evidence demonstrates the requirement of the reciprocal interactions between cortical and thalamic neurons as key for the correct development of functional thalamocortical circuits. This reciprocal loop of connections is essential for sensory processing as well as for the execution of complex sensory-motor tasks. Here, we review recent advances in our understanding of how mutual collaborations between both brain regions define area patterning and cell differentiation in the thalamus and cortex.

Figure 1. Development of corticothalamic and thalamocortical circuits

Developmental time line of thalamocortical and corticothalamic circuits, notice that the upper part of the scheme represents the cortical development timeline (A) and the lower the thalamic one (B). The central core of the scheme is focused in summarizing the CTAs and TCAs navigation. Key developmental time-points and special features are highlighted in the scheme. (A) Cortical development of excitatory neurons takes place from E11.5 to E16.5, at the same time, GABAergic interneurons invade the cortical plate. (B) Thalamic glutamatergic neurons are born between E10.5 and E16.5 at the ventricular zone of the caudal pre-thalamus. GABAergic thalamic interneurons, which origin remains controversial, invade the thalamus during the first postnatal week.

Figure 2. Cortical influence over thalamic development

Schemes representing the interaction between cortex and thalamus at early developmental stages. (A) In the wild type, a sensory representation for each modality (visual, somatosensory and auditory) is represented in both the cortex and thalamus. TCAs are topographically organized in a sensory modality fashion. (B) Modifications of sensory cortical areas promote thalamic rearrangements, either by TCA rewiring or by changing thalamic structures. Ectopic expression of FGF8 at the caudal pole of the cortex generates a duplication of S1, both S1 and S1’ are innervated by TCAs from the VPM nucleus. Reduction of Pax6 expression in the cortex generates a miniaturize S1 cortical area, engaging a reduction of the VPM nucleus. Ablation of COUP-TF1 expression in the cortex produces a shift of cortical areas towards de occipital pole of the cortex, TCAs rewire to properly connect with the shifted cortical territories. POm, Posterior Medial nucleus; LP, Lateral Posterior nucleus; dLG, Dorsal Lateral Geniculate nucleus; MGv, ventral division of the Medial Geniculate body; VPM, Ventral Posterolateral nucleus; TCAs, Thalamocortical axons; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; V1, primary visual cortex; V2, secondary visual cortex; A1, primary auditory cortex.

Figure 3. Bottom-up plasticity. Thalamic influence over cortical arealization and circuitry

Schemes representing the interaction between cortex and thalamus at early developmental stages. (A) In the wild type, a sensory representation for each modality (visual, somatosensory and auditory) is represented in both the cortex and thalamus. Primary and secondary areas are represented in both structures. (B) Ablation or reduction of first-order sensory nuclei of the thalamus engage a bottom-up plasticity, where corresponding primary cortical areas acquire properties of secondary areas. Cross-modal plastic changes are directed by embryonic thalamic activity before sensory onset. Disruption of spontaneous calcium activity in the auditory thalamic nucleus engages an increment of calcium waves in the VPM, producing an increment of the S1 size by augmenting TCA arborisation. POm, Posterior Medial nucleus; LP, Lateral Posterior nucleus; dLG, Dorsal Lateral Geniculate nucleus; MGv, ventral division of the Medial Geniculate body; VPM, Ventral Posterolateral nucleus; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; V1, primary visual cortex; V2, secondary visual cortex; A1, primary auditory cortex.