Glutamate dysfunction associated with developmental cerebellar damage

Relevance to autism spectrum disorders

Eric McKimm, Beau Corkill, Dan Goldowitz, Lorraine Albritton, Ramin Homayouni, Charles D. Blaha, Guy Mittleman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Neural abnormalities commonly associated with autism spectrum disorders include prefrontal cortex (PFC) dysfunction and cerebellar pathology in the form of Purkinje cell loss and cerebellar hypoplasia. It has been reported that loss of cerebellar Purkinje cells results in aberrant dopamine neurotransmission in the PFC which occurs via dysregulation of multisynaptic efferents from the cerebellum to the PFC. Using a mouse model, we investigated the possibility that developmental cerebellar Purkinje cell loss could disrupt glutamatergic cerebellar projections to the PFC that ultimately modulate DA release.We measured glutamate release evoked by local electrical stimulation using fixed-potential amperometry in combination with glutamate selective enzyme-based recording probes in urethane-anesthetized Lurcher mutant and wildtype mice. Target sites included the mediodorsal and ventrolateral thalamic nuclei, reticulotegmental nuclei, pedunculopontine nuclei, and ventral tegmental area. With the exception of the ventral tegmental area, the results indicated that in comparison to wildtype mice, evoked glutamate release was reduced in Lurcher mutants by between 9 and 72% at all stimulated sites. These results are consistent with the notion that developmental loss of cerebellar Purkinje cells drives reductions in evoked glutamate release in cerebellar efferent pathways that ultimately influence PFC dopamine release. Possible mechanisms whereby reductions in glutamate release could occur are discussed.

Original languageEnglish (US)
Pages (from-to)346-353
Number of pages8
JournalCerebellum
Volume13
Issue number3
DOIs
StatePublished - Jan 1 2014

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Prefrontal Cortex
Purkinje Cells
Glutamic Acid
Ventral Tegmental Area
Dopamine
Ventral Thalamic Nuclei
Mediodorsal Thalamic Nucleus
Cerebellar Diseases
Efferent Pathways
Urethane
Synaptic Transmission
Cerebellum
Electric Stimulation
Autism Spectrum Disorder
Pathology
Enzymes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Glutamate dysfunction associated with developmental cerebellar damage : Relevance to autism spectrum disorders. / McKimm, Eric; Corkill, Beau; Goldowitz, Dan; Albritton, Lorraine; Homayouni, Ramin; Blaha, Charles D.; Mittleman, Guy.

In: Cerebellum, Vol. 13, No. 3, 01.01.2014, p. 346-353.

Research output: Contribution to journalArticle

McKimm, E, Corkill, B, Goldowitz, D, Albritton, L, Homayouni, R, Blaha, CD & Mittleman, G 2014, 'Glutamate dysfunction associated with developmental cerebellar damage: Relevance to autism spectrum disorders', Cerebellum, vol. 13, no. 3, pp. 346-353. https://doi.org/10.1007/s12311-013-0541-4
McKimm, Eric ; Corkill, Beau ; Goldowitz, Dan ; Albritton, Lorraine ; Homayouni, Ramin ; Blaha, Charles D. ; Mittleman, Guy. / Glutamate dysfunction associated with developmental cerebellar damage : Relevance to autism spectrum disorders. In: Cerebellum. 2014 ; Vol. 13, No. 3. pp. 346-353.
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