Higher-order thalamocortical circuits are specified by embryonic cortical progenitor types in the mouse brain

• Published in: Cell reports (Cambridge) Vol. 43; no. 5; p. 114157
• Main Authors: Buchan, Matthew J., Gothard, Gemma, Mahfooz, Kashif, van Rheede, Joram J., Avery, Sophie V., Vourvoukelis, Alexios, Demby, Alexander, Ellender, Tommas J., Newey, Sarah E., Akerman, Colin J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.05.2024; Elsevier
• Subjects: Animals; cortex; CP: Neuroscience; development; higher-order; in utero labelling; intermediate progenitor; LIM-Homeodomain Proteins - genetics; LIM-Homeodomain Proteins - metabolism; lineage; Mice; Mice, Inbred C57BL; Neuronal Plasticity - physiology; Neurons - cytology; Neurons - metabolism; Neurons - physiology; optotagging; sensory-evoked plasticity; Somatosensory Cortex - cytology; Somatosensory Cortex - physiology; thalamus; Thalamus - cytology; Thalamus - embryology; Thalamus - physiology; Transcription Factors - metabolism; cortex; lineage; development; CP: Neuroscience; intermediate progenitor; in utero labelling; higher-order; sensory-evoked plasticity; optotagging; thalamus
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114157

The sensory cortex receives synaptic inputs from both first-order and higher-order thalamic nuclei. First-order inputs relay simple stimulus properties from the periphery, whereas higher-order inputs relay more complex response properties, provide contextual feedback, and modulate plasticity. Here, we reveal that a cortical neuron’s higher-order input is determined by the type of progenitor from which it is derived during embryonic development. Within layer 4 (L4) of the mouse primary somatosensory cortex, neurons derived from intermediate progenitors receive stronger higher-order thalamic input and exhibit greater higher-order sensory responses. These effects result from differences in dendritic morphology and levels of the transcription factor Lhx2, which are specified by the L4 neuron’s progenitor type. When this mechanism is disrupted, cortical circuits exhibit altered higher-order responses and sensory-evoked plasticity. Therefore, by following distinct trajectories, progenitor types generate diversity in thalamocortical circuitry and may provide a general mechanism for differentially routing information through the cortex. [Display omitted] •Progenitor type determines an excitatory cortical neuron’s input from thalamus•L4 neurons derived from intermediate progenitors receive more higher-order thalamic input•This reflects progenitor-specified effects upon fine-scale dendritic development•Progenitor-specified circuits dictate higher-order sensory responses and plasticity Buchan et al. demonstrate that the thalamic input received by a layer 4 excitatory cortical neuron in mice is influenced by the neuron’s embryonic progenitor type. Neurons derived from intermediate progenitors receive greater input from higher-order thalamus, which reflects their dendritic morphology and molecular mechanisms specified by the progenitors.