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A new paper by the Akerman Group is published in the journal Cell Reports this week and reveals how fine scale synaptic connectivity in the adult brain is shaped by events during embryonic development.

This image shows a graphical abstract of the new paper from the Akerman group, and illustrates how 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

Cortical neurons in the adult receive and integrate synaptic connections from different thalamic nuclei, which relay distinct types of information. The synaptic inputs from so-called first-order thalamic nuclei are considered the primary relay from the sensory periphery to cortex. In contrast, the synaptic inputs from higher-order thalamic nuclei relay information from multiple cortical and subcortical origins. Consequently, these higher-order inputs can encode more complex contextual information and represent a form of feedback that regulates first-order inputs. Despite their importance, there has been no account as to how cortical neurons receive their higher-order thalamic information.

This new study reveals that a cortical neuron’s higher-order synaptic input is determined by the type of embryonic progenitor from which the neuron is born during development. Neurons born from so-called “intermediate progenitors” go on to receive stronger higher-order thalamic input and exhibit higher-order sensory responses in the adult. These effects result from differences in dendritic morphology and key transcription factors that are specified by the progenitor. When this mechanism is disrupted, adult cortical circuits exhibit abnormal higher-order responses and disrupted sensory-evoked plasticity. These findings reveal that embryonic progenitor types generate distinct synaptic circuits for the differential routing of excitatory information through cortex.

The paper is first authored by Dr Matthew Buchan and is published this week in Cell Reports. The paper is entitled “Higher-order thalamocortical circuits are specified by embryonic cortical progenitor types in the mouse brain” and is available to read here: https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00485-6

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