Differential Innervation of Direct- and Indirect-Pathway Striatal Projection Neurons
Open accessAbstract
The striatum integrates information from multiple brain regions to shape motor learning. The two major projection cell types in striatum target different downstream basal ganglia targets and have opposing effects on motivated behavior, yet differential innervation of these neuronal subtypes is not well understood. To examine whether input specificity provides a substrate for information segregation in these circuits, we used a monosynaptic rabies virus system to generate brain-wide maps of neurons that form synapses with direct- or indirect-pathway striatal projection neurons. We discovered that sensory cortical and limbic structures preferentially innervated the direct pathway, whereas motor cortex preferentially targeted the indirect pathway. Thalamostriatal input, dopaminergic input, as well as input from specific cortical layers, was similar onto both pathways. We also confirm synaptic innervation of striatal projection neurons by the raphe and pedunculopontine nuclei. Together, these findings provide a framework for guiding future studies of basal ganglia circuit function.
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The failure to observe vasopressinergic input to CA2 from the paraventricular nucleus may reflect an inability of the transsynaptic rabies tracing system to label peptidergic inputs.
“we failed to observe vasopressinergic input to CA2 from the paraventricular nucleus of the hypothalamus13, which may reflect an inability of the transsynaptic rabies tracing system to label peptidergic inputs15.”
From The hippocampal CA2 region is essential for social memory (2014) · cites this paper as [15]
The CeA sends a direct, likely inhibitory projection to the striatum.
“It sends a direct, likely inhibitory33, projection to the striatum30,34,35 and is, thus, poised to oppose striatal activity.”
From A dual-pathway architecture for stress to disrupt agency and promote habit (2025) · cites this paper as [34]
DMS D1 and A2A neurons receive projections from BLA and CeA.
“rabies-labeled, DMS D1-projecting cell bodies in the BLA and CeA (right), consistent with prior reports30,34.”
From A dual-pathway architecture for stress to disrupt agency and promote habit (2025) · cites this paper as [34]
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- Authors
- Wall, N. R., De La Parra, M., Callaway, E. M., & Kreitzer, A. C.
- Affiliations
- Salk Institute for Biological Studies (US)
- Gladstone Institutes (US)
- Corresponding author
- Callaway, Edward M.
- Kreitzer, Anatol C.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 79
- Issue
- 2
- Pages
- 347-360
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3729794
- OpenAlex
- W2074651284
- Cited by
- 489
- References
- 69
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 39 · 2023: 40 · 2022: 28 · 2021: 44 · 2020: 38 · 2019: 36 · 2018: 42 · 2017: 48 · 2016: 53 · 2015: 34 · 2014: 32 · 2013: 3
- FWCI
- 25.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Gatsby Charitable Foundation
- National Institutes of Health
- National Institute of Mental Health (MH063912, R01MH063912)
- National Institute on Drug Abuse (P01DA010154, DA-010154)
- National Institute of Neurological Disorders and Stroke (NS064984, R01NS078435, R01NS064984)
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- striatum, direct pathway, indirect pathway, striatal projection neurons, synaptic innervation, basal ganglia, dopaminergic input, motor cortex, sensory cortex, limbic structures, raphe nuclei, information segregation, motor learning
- MeSH terms
- Animals, Cerebral Cortex, Corpus Striatum, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Neural Pathways, Neurons, Mice, HEK293 Cells
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