Completed Brain & Nervous System Cells, Biochemistry & Physiology

General principles underlying the assembly of cortical inhibitory circuits.

Funder Wellcome Charity-funded
Recipient organisation King's College London
Funding £2.7M
Period Jul 2014 — Dec 2019

In plain English

AI plain-English summary

The cerebral cortex contains two broad classes of neurons—excitatory pyramidal cells and inhibitory interneurons—that must wire together into precise microcircuits during development, but the rules governing this assembly remain unknown. This matters because the brain’s ability to process information, generate thoughts, and coordinate movement depends on the balance between excitation and inhibition. Pyramidal cells make up about 80% of cortical neurons and transmit signals between brain regions, while interneurons provide inhibitory control that shapes rhythmic brain activity. How dozens of distinct interneuron types find their correct partners and positions within cortical layers and columns is a fundamental gap in neuroscience. This is curiosity-driven fundamental science with no immediate practical application. However, understanding the general principles of circuit assembly could eventually illuminate what goes wrong in neurodevelopmental conditions such as epilepsy, schizophrenia, or autism, where inhibitory circuit dysfunction is implicated. Past discoveries in fundamental neuroscience—such as the principles of synaptic plasticity—have led to treatments for brain disorders decades later. A deeper grasp of how inhibitory circuits are built may similarly open unexpected avenues for future therapies.

View original technical description
One of the major goals of neuroscience is to understand how brain function emerges through the assembly of specific neuronal circuits. This is particularly challenging ffor the cerebral cortex, where dozens of different classes of neurons converge during development to form specific microcircuits. The cerebral cortex contain two main classes of neurons: excitatory glutamatergic pyramidalcells and inhibitory gamma-aminobutyric acid-containing (GABAergic) interneurons. Pyramidal cells constitute approximately 80% of cortical neurons and they specialise in transmitting information between different cortical regions and to other regions of the brain. Interneurons comprise a highly heterogeneous group of neurons that provide inhibitory inputs and shape different forms of synchronised oscillations. Pyramidal cells and interneurons are organised along two main dimensions in the cerebral cortex. A first axis (tangential organisation) divides the cortex into a variable number of layers depending on the cortical area. Neurons within the same cortical layer share important features, including general patterns of connectivity. The second axis (radial organisation) reflects the vertical arrangement of neuronal circuits within a column of cortical tissue. The neurons within a given column are stereotypically interconnected in the vertical dimension, share extrinsic connectivity and function as the basic units underlying cortical operations.

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Researchers

Oscar Marín (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Developmental principles for the functional specialisation of inhibitory circuits in neocortical areas
Molecular Mechanisms of Neuronal Diversification and Cortical Circuit Assembly
Assembly and organisation of inhibitory networks in the cerebral cortex
The emergence of GABAergic microcircuits in the cortex
Functional neuromics of the cerebral cortex.

Original classification

Investigator Award in Science

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