Authors: Eric McKimm Beau Corkill Dan Goldowitz Lorraine M Albritton Ramin Homayouni Charles D Blaha Guy Mittleman
Publish Date: 2013/12/05
Volume: 13, Issue: 3, Pages: 346-353
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 fixedpotential amperometry in combination with glutamate selective enzymebased recording probes in urethaneanesthetized 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
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