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Untangling the cortico-thalamo-cortical loop: cellular pieces of a knotty circuit puzzle

Nature Reviews Neuroscience volume 22, pages 389–406 (2021)Cite this article

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Abstract

Functions of the neocortex depend on its bidirectional communication with the thalamus, via cortico-thalamo-cortical (CTC) loops. Recent work dissecting the synaptic connectivity in these loops is generating a clearer picture of their cellular organization. Here, we review findings across sensory, motor and cognitive areas, focusing on patterns of cell type-specific synaptic connections between the major types of cortical and thalamic neurons. We outline simple and complex CTC loops, and note features of these loops that appear to be general versus specialized. CTC loops are tightly interlinked with local cortical and corticocortical (CC) circuits, forming extended chains of loops that are probably critical for communication across hierarchically organized cerebral networks. Such CTC–CC loop chains appear to constitute a modular unit of organization, serving as scaffolding for area-specific structural and functional modifications. Inhibitory neurons and circuits are embedded throughout CTC loops, shaping the flow of excitation. We consider recent findings in the context of established CTC and CC circuit models, and highlight current efforts to pinpoint cell type-specific mechanisms in CTC loops involved in consciousness and perception. As pieces of the connectivity puzzle fall increasingly into place, this knowledge can guide further efforts to understand structure–function relationships in CTC loops.

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Fig. 1: Major classes of excitatory projection neurons in cortico-thalamo-cortical loops.
Fig. 2: Cell type-specific cortico-thalamo-cortical connectivity matrices across areas.
Fig. 3: Patterns and types of circuit connections in cortico-thalamo-cortical loops.
Fig. 4: Cortico-thalamo-cortical loops are interconnected with local cortical circuits and corticocortical circuits, via hub-like intratelencephalic neurons.
Fig. 5: Cortico-thalamo-cortical loops in the context of hierarchical models of cortical organization.
Fig. 6: Inhibition in cortico-thalamo-cortical loops.
Fig. 7: Cortico-thalamo-cortical loop connectivity with the diverse types of matrix axon arborizations.

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Acknowledgements

The authors thank L. Acsády, J. M. Barrett, S. Brown, J. Huguenard and L. Petreanu for comments and suggestions.

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  1. Naoki Yamawaki

    Present address: Department of Biomedicine, Aarhus University, Aarhus, Denmark

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  1. Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Gordon M. G. Shepherd & Naoki Yamawaki

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Glossary

Hierarchical organization

As applied to cerebral organization, this term refers to the concept of feedforward and feedback streams of information processing across areas and regions, reflected in distinct patterns of axonal projections.

Monosynaptic

A synaptic circuit connection from one neuron or set of neurons to another that is direct, with no other intervening neurons in the circuit.

Polysynaptic

A synaptic circuit connection from one neuron or set of neurons to another that is indirect, because it involves connections to other intervening neurons in the circuit.

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Shepherd, G.M.G., Yamawaki, N. Untangling the cortico-thalamo-cortical loop: cellular pieces of a knotty circuit puzzle. Nat Rev Neurosci 22, 389–406 (2021). https://doi.org/10.1038/s41583-021-00459-3

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