A comprehensive excitatory input map of the striatum reveals novel functional organization
Open accessAbstract
The striatum integrates excitatory inputs from the cortex and the thalamus to control diverse functions. Although the striatum is thought to consist of sensorimotor, associative and limbic domains, their precise demarcations and whether additional functional subdivisions exist remain unclear. How striatal inputs are differentially segregated into each domain is also poorly understood. This study presents a comprehensive map of the excitatory inputs to the mouse striatum. The input patterns reveal boundaries between the known striatal domains. The most posterior striatum likely represents the 4th functional subdivision, and the dorsomedial striatum integrates highly heterogeneous, multimodal inputs. The complete thalamo-cortico-striatal loop is also presented, which reveals that the thalamic subregions innervated by the basal ganglia preferentially interconnect with motor-related cortical areas. Optogenetic experiments show the subregion-specific heterogeneity in the synaptic properties of striatal inputs from both the cortex and the thalamus. This projectome will guide functional studies investigating diverse striatal functions.
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LOFC neurons send inputs to a subregion of striatum ranging from dorsomedial to central striatum, with dense inputs in the central subregion.
“Consistently, it has repeatedly been reported that LOFC neurons send inputs to a subregion of the striatum ranging from the dorsomedial to the central striatum. Dense inputs are observed in the central subregion60–63.”
From Dissociable roles of prefrontal plasticity in decision-making strategy and execution of habitual behavior (2026) · cites this paper as [60]
The Results section on clustered striatal subdivisions (page unavailable) identifies LO/VO as a primary input to the dorsomedial striatum. But the Results section on corticostriatal input distribution patterns places its dense projections in the anterior, medial striatum and describes broader projections as diffuse; it does not support dense LO/VO inputs in a central subregion. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRecent histological analyses revealed distinct projections to striatal regions from each cortical region, suggesting these histologically separated pathways have distinct functions.
“However, recent histological analyses revealed distinct projections to striatal regions from each cortical region59,60 suggesting that these histologically separated pathways have distinct functions.”
From Dissociable roles of prefrontal plasticity in decision-making strategy and execution of habitual behavior (2026) · cites this paper as [60]
Execution of motor behavior is controlled by top-down projections from cortical areas to the dorsal striatum, which form strong excitatory synaptic connections onto striatal output neurons.
“The execution of motor behavior is controlled by top-down projections from cortical areas to the dorsal striatum (caudate putamen in primates), which form strong excitatory synaptic connections onto striatal output neurons [3][4][5].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [4]
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“According to previous studies 58 – 60 , the location of CS is de fi ned as the intermediate zone between the dorsomedial striatum and the dorso-lateral striatum on the mediolateral axis, and between the dorsal striatum and the ventral striatum on the dorsoventral axis.”
- Authors
- Hunnicutt, B. J., Jongbloets, B. C., Birdsong, W. T., Gertz, K. J., Zhong, H., & Mao, T.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- Mao, Tianyi
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-11-28
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5207773
- OpenAlex
- W2558788280
- Cited by
- 536
- References
- 73
- Citations by year
- 2026: 50 · 2025: 76 · 2024: 63 · 2023: 64 · 2022: 57 · 2021: 65 · 2020: 55 · 2019: 51 · 2018: 39 · 2017: 16
- FWCI
- 26.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation
- National Institute of Mental Health (DP2OD008425)
- National Institute of Neurological Disorders and Stroke (U01NS094247, R01NS081071)
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- striatum, dorsomedial striatum, thalamic subregions, synaptic properties, basal ganglia, mouse striatum
- MeSH terms
- Animals, Brain Mapping, Corpus Striatum, Mice, Optogenetics
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