Thalamocortical connectivity is crucial for conscious perception in mammals, involving precise circuitry between the cerebral cortex and thalamus. The development and evolution of these structures are closely linked, with thalamocortical axons (TCAs) navigating through the forebrain during development. The organization of the pallial–subpallial boundary (PSPB) varies among mammals, reptiles, and birds, influencing TCA pathfinding. Early TCA guidance relies on interactions with transient cell populations in the internal capsule and subplate neurons, which help navigate through the PSPB. Thalamocortical axons initially pattern cortical areas genetically, then innervate the cortex in a topographic manner to refine sensory input.
The thalamus and six-layered isocortex form functional circuits that process sensory input, regulate brain state, and perform higher cognitive functions. Thalamocortical circuits and their abnormalities are important for understanding sensory perception, brain state control, and sleep, with implications for neurological and psychiatric conditions. The guidance of early thalamocortical projections involves multiple mechanisms along their trajectory, with the DTB and PSPB being particularly vulnerable. Guidepost cells in the prethalamus and thalamic reticular nucleus form precocious projections that assist TCA pathfinding.
The crossing of the PSPB is a major challenge for ascending thalamocortical projections. The PSPB is first established as a gene expression boundary, with radial glial fascicles and dense cell packs influencing TCA passage. Corticothalamic and thalamocortical projections grow toward the PSPB at similar developmental stages, with pioneer corticofugal axons arriving before thalamic axons. These axons cofasculate to cross the nonpermissive PSPB, guided by the "handshake hypothesis," where descending and ascending axons guide each other through this region.
The "handshake" hypothesis is supported by in vivo observations and in vitro studies, showing that descending axons are necessary for area-specific connectivity. Conditional deletion studies confirm the role of cortical efferents in guiding TCA pathfinding across the PSPB. Subplate neurons are crucial for this process, with their absence leading to TCA defects. Thalamocortical axons accumulate in the subplate zone before invading the cortical plate, with the "waiting" period allowing for refinement of connections.
Genetic studies using subplate-spared gene manipulation reveal the role of subplate neurons in TCA guidance, with Arid1a expression being essential for "handshake" interactions. The evolution of the PSPB reflects changes in migratory streams, with differences in tangential migration between mammals and birds. The claustrum and other structures in mammals differ from those in birds and reptiles, highlighting the importance of genetic changes in early forebrain development.
Thalamocortical connectivity is also regulated by the hierarchy of thalamic nuclei, with first-order nucleiThalamocortical connectivity is crucial for conscious perception in mammals, involving precise circuitry between the cerebral cortex and thalamus. The development and evolution of these structures are closely linked, with thalamocortical axons (TCAs) navigating through the forebrain during development. The organization of the pallial–subpallial boundary (PSPB) varies among mammals, reptiles, and birds, influencing TCA pathfinding. Early TCA guidance relies on interactions with transient cell populations in the internal capsule and subplate neurons, which help navigate through the PSPB. Thalamocortical axons initially pattern cortical areas genetically, then innervate the cortex in a topographic manner to refine sensory input.
The thalamus and six-layered isocortex form functional circuits that process sensory input, regulate brain state, and perform higher cognitive functions. Thalamocortical circuits and their abnormalities are important for understanding sensory perception, brain state control, and sleep, with implications for neurological and psychiatric conditions. The guidance of early thalamocortical projections involves multiple mechanisms along their trajectory, with the DTB and PSPB being particularly vulnerable. Guidepost cells in the prethalamus and thalamic reticular nucleus form precocious projections that assist TCA pathfinding.
The crossing of the PSPB is a major challenge for ascending thalamocortical projections. The PSPB is first established as a gene expression boundary, with radial glial fascicles and dense cell packs influencing TCA passage. Corticothalamic and thalamocortical projections grow toward the PSPB at similar developmental stages, with pioneer corticofugal axons arriving before thalamic axons. These axons cofasculate to cross the nonpermissive PSPB, guided by the "handshake hypothesis," where descending and ascending axons guide each other through this region.
The "handshake" hypothesis is supported by in vivo observations and in vitro studies, showing that descending axons are necessary for area-specific connectivity. Conditional deletion studies confirm the role of cortical efferents in guiding TCA pathfinding across the PSPB. Subplate neurons are crucial for this process, with their absence leading to TCA defects. Thalamocortical axons accumulate in the subplate zone before invading the cortical plate, with the "waiting" period allowing for refinement of connections.
Genetic studies using subplate-spared gene manipulation reveal the role of subplate neurons in TCA guidance, with Arid1a expression being essential for "handshake" interactions. The evolution of the PSPB reflects changes in migratory streams, with differences in tangential migration between mammals and birds. The claustrum and other structures in mammals differ from those in birds and reptiles, highlighting the importance of genetic changes in early forebrain development.
Thalamocortical connectivity is also regulated by the hierarchy of thalamic nuclei, with first-order nuclei