Connecting the dots of the cerebro-cerebellar role in cognitive function

Neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex

Tiffany D. Rogers, Price E. Dickson, Detlef Heck, Dan Goldowitz, Guy Mittleman, Charles D. Blaha

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Cerebellar involvement in autism, schizophrenia, and other cognitive disorders is typically associated with prefrontal cortical pathology. However, the underlying neuronal mechanisms are largely unknown. It has previously been shown in mice that stimulation of the dentate nucleus (DN) of the cerebellum evokes dopamine (DA) release in the medial prefrontal cortex (mPFC). Here, we investigated the neuronal circuitry by which the cerebellum modulates mPFC DA release. Fixed potential amperometry was used to determine the contribution of two candidate pathways by which the cerebellum may modulate mPFC DA release. In urethane anesthetized mice, DA release evoked by DN stimulation (50 Hz) was recorded in mPFC following local anesthetic lidocaine (0.02 μg) or ionotropic glutamate receptor antagonist kynurenate (0.5 μg) infusions into the mediodorsal or ventrolateral thalamic nucleus (ThN md; ThN vl), or the ventral tegmental area (VTA). Following intra-VTA lidocaine or kynurenate infusions, DA release was decreased by ~50%. Following intra-ThN md and ThN vl infusions of either drug, DA release was decreased by ~35% and 15%, respectively. Reductions in DA release following lidocaine or kynurenate infusions were not significantly different indicating that neuronal cells in the VTA and ThN were activated primarily if not entirely by glutamatergic inputs. The present study suggests that neuropathological changes in the cerebellum commonly observed in autism, schizophrenia, and other cognitive disorders could result in a loss of functionality of cerebellar-mPFC circuitry that is manifested as aberrant dopaminergic activity in the mPFC. Additionally, these results specifically implicate glutamate as a modulator of mPFC dopaminergic activity.

Original languageEnglish (US)
Pages (from-to)1204-1212
Number of pages9
JournalSynapse
Volume65
Issue number11
DOIs
StatePublished - Nov 1 2011

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Prefrontal Cortex
Cognition
Dopamine
Kynurenic Acid
Cerebellum
Ventral Tegmental Area
Lidocaine
Cerebellar Nuclei
Autistic Disorder
Schizophrenia
Ventral Thalamic Nuclei
Mediodorsal Thalamic Nucleus
Ionotropic Glutamate Receptors
Excitatory Amino Acid Antagonists
Urethane
Local Anesthetics
Glutamic Acid
Pathology

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Connecting the dots of the cerebro-cerebellar role in cognitive function : Neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex. / Rogers, Tiffany D.; Dickson, Price E.; Heck, Detlef; Goldowitz, Dan; Mittleman, Guy; Blaha, Charles D.

In: Synapse, Vol. 65, No. 11, 01.11.2011, p. 1204-1212.

Research output: Contribution to journalArticle

Rogers, Tiffany D. ; Dickson, Price E. ; Heck, Detlef ; Goldowitz, Dan ; Mittleman, Guy ; Blaha, Charles D. / Connecting the dots of the cerebro-cerebellar role in cognitive function : Neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex. In: Synapse. 2011 ; Vol. 65, No. 11. pp. 1204-1212.
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