Cell Type-Specific Circuit Mapping Reveals the Presynaptic Connectivity of Developing Cortical Circuits.

Area of Science:

• Neuroscience
• Developmental Biology
• Systems Neuroscience

Background:

• Mapping cell type-specific neuronal connectivity in the mammalian cerebral cortex in vivo is a significant challenge.
• Understanding the development of excitatory and inhibitory interneuron presynaptic input is crucial for comprehending early cortical network formation.

Purpose of the Study:

• To analyze the development of neuronal connectivity in the cerebral cortex during the first postnatal month using a murine model.
• To investigate the connectivity of Cajal-Retzius (CR) cells, critical for cortical layer formation and early network establishment.
• To characterize the refinement of excitatory and inhibitory inputs onto major neuronal populations in the developing cortex.

Main Methods:

• Utilized a murine model to study the first postnatal month of cortical development.
• Surveyed connectivity of Cajal-Retzius cells, focusing on inputs received and provided.
• Employed Cre drivers to label neuronal progenitors and study discrete neuronal populations in older cortex.
• Assessed inputs onto inhibitory interneurons and excitatory projection neurons at different developmental stages.

Main Results:

• Cajal-Retzius cells receive inputs from deeper-layer excitatory neurons and inhibitory interneurons in the first postnatal week.
• Excitatory pyramidal neurons and inhibitory interneurons receive broad inputs, including from CR cells, in the first postnatal week.
• Excitatory cortical and subcortical inputs onto inhibitory interneurons and excitatory projection neurons are refined by the fourth postnatal week.
• Local inhibitory inputs onto these neuronal populations increase during this postnatal period.

Conclusions:

• Cell type-specific circuit mapping is an effective method for determining cortical connectivity with molecular subtype precision.
• The study provides a systematic analysis of presynaptic connections of discrete neuronal subtypes in the developing and mature cerebral cortex.
• Findings elucidate the dynamic changes in excitatory and inhibitory circuit development during early postnatal life.