Cerebellar modulation of frontal cortex dopamine efflux in mice: Relevance to autism and schizophrenia
Open accessAbstract
Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 μA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co‐occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders. Synapse 62:544–550, 2008. © 2008 Wiley‐Liss, Inc.
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Recent studies report cerebellar control of dopamine release in prefrontal cortex, a mechanism that might be triggered by spatiotemporal cortical activity patterns.
“Important new clues, however, come from recent studies reporting cerebellar control of dopamine release in the prefrontal cortex [179, 180], a mechanism that might be triggered by spatiotemporal cortical activity patterns, as proposed here.”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [180]
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- Authors
- Mittleman, G., Goldowitz, D., Heck, D. H., & Blaha, C. D.
- Affiliations
- University of Memphis (US)
- University of Tennessee Health Science Center (US)
- Corresponding author
- Blaha, Charles D.
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 2008-04-24
- Volume
- 62
- Issue
- 7
- Pages
- 544-550
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- PMC
- PMC3854870
- OpenAlex
- W2094121582
- Cited by
- 111
- References
- 46
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 11 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 10 · 2018: 9 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 8 · 2013: 10 · 2012: 6
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Synapse (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Autism Speaks (AS1780)
- National Institute of Neurological Disorders and Stroke (R01NS063009)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03HD057244)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- cerebellum, prefrontal cortex, dopamine efflux, Purkinje cells, dentate nucleus, cerebellar stimulation, autism spectrum disorder, schizophrenia, developmental disorders, dopamine reuptake
- MeSH terms
- Animals, Autistic Disorder, Cerebellar Nuclei, Cerebellum, Dopamine, Electric Stimulation, Frontal Lobe, Mice, Neurologic Mutants, Mice, Transgenic, Neural Pathways, Synaptic Transmission, Purkinje Cells, Schizophrenia, Prefrontal Cortex, Presynaptic Terminals, Mice
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