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Corticostriatal connectivity and its role in disease

Nature Reviews Neuroscience volume 14, pages 278–291 (2013)Cite this article

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Key Points

  • Corticostriatal (CStr) projections are formed by two distinct classes of cortical pyramidal neurons: intratelencephalic (IT) and pyramidal tract (PT) neurons. IT and PT neurons are highly differentiated at multiple levels, including long-range axonal projections, local cortical circuits, intrinsic electrical properties, neuromodulatory mechanisms and molecular profiles.

  • Many neurological and neuropsychiatric diseases involve dysfunction in the CStr system. In several of these, evidence is accumulating for specific changes in the functional properties of IT and PT neurons and their circuits.

  • Autism appears to involve changes especially in IT neurons and networks.

  • Amyotrophic lateral sclerosis involves degeneration of corticospinal neurons, a major subtype of PT neurons.

  • In Parkinson's disease, a hypokinetic movement disorder, PT neurons are particularly implicated in the disease process. The therapeutic efficacy of deep brain stimulation in the subthalamic nucleus has been ascribed to antidromic activation of PT neurons in the cortex. In Huntington's disease, a hyperkinetic movement disorder, CStr changes suggest both IT and PT involvement.

  • CStr changes are prominent in neuropsychiatric disorders such as schizophrenia and obsessive-compulsive disorder. In major depression, animal studies point to IT specificity.

  • Collectively the evidence suggests that 'IT/PT imbalance' may be a useful concept for guiding further research into diseases involving CStr dysfunction. The distinct properties of IT and PT neurons present abundant opportunities for developing cell type-specific interventions in these disorders.

Abstract

Corticostriatal projections are essential components of forebrain circuits and are widely involved in motivated behaviour. These axonal projections are formed by two distinct classes of cortical neurons, intratelencephalic (IT) and pyramidal tract (PT) neurons. Convergent evidence points to IT versus PT differentiation of the corticostriatal system at all levels of functional organization, from cellular signalling mechanisms to circuit topology. There is also growing evidence for IT/PT imbalance as an aetiological factor in neurodevelopmental, neuropsychiatric and movement disorders — autism, amyotrophic lateral sclerosis, obsessive-compulsive disorder, schizophrenia, Huntington's and Parkinson's diseases and major depression are highlighted here.

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Figure 1: Long-range axonal projections define two classes of CStr neurons.
Figure 2: Intracortical circuits are IT- and PT-specific and hierarchical.
Figure 3: IT and PT neurons have extensively differentiated intrinsic electrophysiology, neuromodulatory properties and molecular profiles.
Figure 4: IT versus PT innervation of striatum may be differentiated along multiple dimensions of striatal circuit organization.
Figure 5: CStr-related changes in ASD, ALS and MDD.
Figure 6: CStr-related changes in OCD and schizophrenia involve subsets of CStr circuits, with some overlap.
Figure 7: CStr changes are prominent in HD and PD but the differential involvement of IT and PT neurons is not fully understood.

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Acknowledgements

I am grateful to M. D. Bevan, D. J. Surmeier and K. Svoboda for comments and suggestions, and to T. Kiritani for the image in figure 1. G.M.G.S. is supported by the US National Institutes of Health/National Institute of Neurological Disorders and Stroke grant NS061963.

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    Gordon M. G. Shepherd

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Glossary

Recurrent connectivity

The concept that neurons within a class connect with one another, implying feedback communication within the network.

Hierarchical connectivity

The concept that one class of neurons is functionally downstream from another. The two classes may be in separate areas or locally intermingled. This feedforward arrangement implies control of the downstream population by the upstream population.

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Shepherd, G. Corticostriatal connectivity and its role in disease. Nat Rev Neurosci 14, 278–291 (2013). https://doi.org/10.1038/nrn3469

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