Cerebellar Projections to the Prefrontal Cortex of the Primate
Open accessAbstract
The cerebellum is known to project via the thalamus to multiple motor areas of the cerebral cortex. In this study, we examined the extent and anatomical organization of cerebellar input to multiple regions of prefrontal cortex. We first used conventional retrograde tracers to map the origin of thalamic projections to five prefrontal regions: medial area 9 (9m), lateral area 9 (9l), dorsal area 46 (46d), ventral area 46, and lateral area 12. Only areas 46d, 9m, and 9l received substantial input from thalamic regions included within the zone of termination of cerebellar efferents. This suggested that these cortical areas were the target of cerebellar output. We tested this possibility using retrograde transneuronal transport of the McIntyre-B strain of herpes simplex virus type 1 from areas of prefrontal cortex. Neurons labeled by retrograde transneuronal transport of virus were found in the dentate nucleus only after injections into areas 46d, 9m, and 9l. The precise location of labeled neurons in the dentate varied with the prefrontal area injected. In addition, the dentate neurons labeled after virus injections into prefrontal areas were located in regions spatially separate from those labeled after virus injections into motor areas of the cerebral cortex. Our observations indicate that the cerebellum influences several areas of prefrontal cortex via the thalamus. Furthermore, separate output channels exist in the dentate to influence motor and cognitive operations. These results provide an anatomical substrate for the cerebellum to be involved in cognitive functions such as planning, working memory, and rule-based learning.
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Reciprocal connections between neocortical motor and non-motor association areas and the cerebellum have been carefully mapped out.
“Reciprocal connections between neocortical motor and non-motor association areas and the cerebellum have also been carefully mapped out [211, 212].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [212]
Polysynaptic connections between the cerebellum and the cortex have been demonstrated in anatomic tracing and functional connectivity studies.
“Polysynaptic connections between the cerebellum and the cortex have been demonstrated both in anatomic tracing studies and functional connectivity studies9,10,11,12,13.”
From Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits (2020) · cites this paper as [10]
Connectivity exists between the left mPFC and Rcrus1 in humans and primates.
“We and others previously demonstrated connectivity between the left mPFC and Rcrus1 in humans and primates8,9,10.”
From Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits (2020) · cites this paper as [10]
Functional connections exist between the cerebellar cortex and cerebral cortical areas in the regulation of complex non-motor behavior.
“support functional connections between the cerebellar cortex and cerebral cortical areas in the regulation of complex non-motor behavior3,9,10,19.”
From Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits (2020) · cites this paper as [10]
These patterns of size-independently co-evolving brain structures correspond to brain systems that have been described in electrophysiological and anatomical tract-tracing studies in non-human primates and MRI studies in humans.
“These patterns of size-independently co-evolving brain structures correspond to brain systems that have been described in electrophysiological and anatomical tract-tracing studies in non-human primates [27–31] and MRI studies in humans [32–35]”
From Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution (2013) · cites this paper as [28]
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- Authors
- Middleton, F. A., & Strick, P. L.
- Affiliations
- United States Department of Veterans Affairs (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-01-15
- Volume
- 21
- Issue
- 2
- Pages
- 700-712
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763818
- OpenAlex
- W2149795074
- Cited by
- 1,034
- References
- 5
- Citations by year
- 2026: 33 · 2025: 31 · 2024: 41 · 2023: 38 · 2022: 52 · 2021: 47 · 2020: 43 · 2019: 43 · 2018: 35 · 2017: 46 · 2016: 40 · 2015: 45 · 2014: 48 · 2013: 55 · 2012: 49
- FWCI
- 16.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- U.S. Public Health Service
- National Institute of Mental Health (MH-48185, R01MH056661, MH11262, F31MH011262, MH-56661, P50MH048185)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
- Keywords
- cerebellum, prefrontal cortex, thalamocortical connections, dentate nucleus, area 46, retrograde tracing, herpes simplex virus type 1, transneuronal transport, cognitive function, working memory, rule-based learning
- MeSH terms
- Animals, Brain Mapping, Cebus, Cerebellar Nuclei, Cerebellum, Fluorescent Dyes, Neural Pathways, Neurons, Thalamus, Prefrontal Cortex, Herpesvirus 1, Human
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