Cerebellar Projections to the Prefrontal Cortex of the Primate

By F. Middleton, Peter Strick. Journal of Neuroscience, 2001

1,020 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Neurology, Sensory Systems

View Paper: https://www.semanticscholar.org/paper/7fe3b965772e95c4c147e32a73225c2f56312d86

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Citations in the corpus

Cerebellum and nonmotor function. (2009, background): “However, our injection sites into area 46 display little or no overlap with the prefrontal eye field (compare figure 2 in Middleton & Strick 2001 with figure 2 in Tian & Lynch 1996).”
An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. (2003, background): “It is now clear that the anatomical substrate exists for cerebellar output to influence nonmotor as well as motor areas of the cerebral cortex (Clower et al. 2001; Hoover and Strick 1999; Middleton and Strick 1998, 2001).”
Cerebellar networks with the cerebral cortex and basal ganglia. (2013, background): “of prefrontal and posterior parietal cortex are targets of cerebellar output (Figure 2) [8, 9, 12, 16, 24].”
Functional Topography of the Cerebellum in Verbal Working Memory (2010, background): “Ventral portions of the cerebellar output dentate nuclei connect with dorsolateral prefrontal regions (BA 9/46) implicated in working memory and executive control (Dum and Strick 2003; Kelly and Strick 2003; Middleton and Strick 2001).”
The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. (2013, background): “Strick and colleagues resolved the issue by using transneuronal tracing to observe both input and output projections between the cerebellum and cerebral association cortex (Middleton and Strick, 1994, 2001; Kelly and Strick, 2003; see Bostan et al., 2013 for review).”
Cerebellar Loops with Motor Cortex and Prefrontal Cortex of a Nonhuman Primate (2003, methodology): “…we used retrograde transneuronal transport of HSV1 to examine the organization of dentate projections to areas of motor, premotor, oculomotor, prefrontal, and posterior parietal cortex (Hoover and Strick, 1993, 1999; Lynch et al., 1994; Middleton and Strick, 1994, 2001; Clower et al., 2001).”
Functional grouping and cortical-subcortical interactions in emotion: A meta-analysis of neuroimaging studies (2008, neutral): “The CB is connected with specific prefrontal regions in topographically mapped reciprocal circuits (Middleton and Strick, 1994, 2000) and with “limbic” regions, including the Hy (Haines and Dietrichs, 1984), OFC, dmPFC, portions of IFG, and inferior frontal convexity (BA 46/12) (Middleton and Strick”
Consensus Paper: Pathological Role of the Cerebellum in Autism (2012, background): “Reciprocal connections between neocortical motor and non-motor association areas and the cerebellum have also been carefully mapped out [211, 212].”
The teen brain: insights from neuroimaging. (2008, background): “However a converging body of evidence from electroencephalography (EEG) studies [8], fMRI studies [9], studies in subjects with vascular and degenerative cerebellar disease [10,11], and histologic studies demonstrating cerebellar connections to dorsolateral prefrontal cortex, the medial frontal cort”
Structural brain imaging of attention-deficit/hyperactivity disorder. (2005, background): “Additionally, Middleton and Strick (2001) have demonstrated cerebellar–cortical connections that provide an anatomic substrate for a cerebellar–prefrontal circuit in the pathophysiology of ADHD.”
Distinct Cerebellar Contributions to Intrinsic Connectivity Networks (2009, background): “…2009 Society for Neuroscience 0270-6474/09/298586-09$15.00/0 substantiated prominent connections from associative and limbic cortices and hypothalamus to the neocerebellum (including the dentate nuclei) (Schmahmann, 1996; Haines et al., 1997; Middleton and Strick, 1997, 2001; Dum and Strick, 2003).”