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The thalamus, often called “the gateway to the cerebral cortex,” is vital in processing and directing sensory and motor signals throughout the brain. Almost all inputs destined for the cerebral cortex, except for olfactory signals, are relayed through the thalamus. The thalamus is  a sophisticated relay station, channeling information from various brain regions to the cerebral cortex, as well as a filter, prioritizing certain signals over others based on current physiological...
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The diencephalon, etymologically translated as 'through brain,' plays an integral role as the conduit between the cerebrum and the vast extent of the nervous system. However, the olfactory system is an exception, as it interfaces directly with the cerebrum. The diencephalon, deeply ensconced beneath the cerebrum, primarily consists of three paired structures — the thalamus, hypothalamus, and epithelamus. It also includes accessory structures such as the subthalamus, which houses...
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Sensory impulses related to touch, pressure, vibration, and proprioception from various body parts, such as the limbs, trunk, neck, and posterior head, travel to the cerebral cortex through the posterior column-medial lemniscus pathway. The pathway’s name derives from the two white-matter tracts that convey the impulses: the spinal cord's posterior column and the brainstem's medial lemniscus. First-order sensory neurons extend their axons into the spinal cord, forming the...
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Ex utero Electroporation and Whole Hemisphere Explants: A Simple Experimental Method for Studies of Early Cortical Development
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Progression of Cortical Layer 6 Input to First-Order Thalamic Nuclei and the Thalamic Reticular Nucleus During

Guela Sokhadze1,2, Gubbi Govindaiah1, Peter Campbell1,3

  • 1Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky, USA.

The European Journal of Neuroscience
|March 18, 2025
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Summary

Layer 6 (L6) corticothalamic (CT) projections to the thalamus develop in a coordinated sequence. Connections in the thalamic reticular nucleus (TRN) mature before those in first-order thalamic nuclei like the ventrobasal complex (VB) and dorsal lateral geniculate nucleus (dLGN).

Keywords:
Layer 6corticothalamicdevelopmentdorsal lateral geniculate nucleusthalamic reticular nucleusventrobasal complex

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Systems Neuroscience

Background:

  • Layer 6 (L6) neurons in the neocortex form major excitatory projections to the thalamus.
  • Corticothalamic (CT) projections interact with the thalamic reticular nucleus (TRN), influencing thalamocortical signaling.
  • The developmental timeline of L6 CT connections in the TRN and thalamic nuclei is largely unknown.

Purpose of the Study:

  • To investigate the developmental timing of L6 CT axon innervation and functional synapse formation in the TRN and first-order thalamic nuclei (VB, dLGN).
  • To characterize the maturation of synaptic function in these developing connections.

Main Methods:

  • Utilized L6-specific Ntsr1-Cre mouse lines crossed with Cre-dependent reporters (Ai9, Ai32) to visualize and electrophysiologically assess CT projections.
  • Employed in vivo imaging of tdTomato-labeled CT axons and ex vivo acute slice electrophysiology with optogenetics to record synaptic responses.

Main Results:

  • L6 CT axons innervated the TRN and ventrolateral VB by postnatal day (P)2-3, expanding to all of VB by P7.
  • Innervation of the dorsal lateral geniculate nucleus (dLGN) progressed from ventral to dorsal between P7 and P14.
  • Functional excitatory postsynaptic responses appeared sequentially in TRN (P7), VB (P7-10), and dLGN (P10-14), initially weak and maturing with age, showing synaptic facilitation.

Conclusions:

  • L6 cortical innervation of the thalamus is a highly coordinated developmental process.
  • Connections within the TRN mature earlier than those in first-order thalamic nuclei (VB, dLGN).
  • This developmental sequence suggests a specific order for the establishment of modulatory feedback circuits in the thalamus.