Cerebellar Circuitry in Autism (funded through NAAR)

Neuropathological studies in autistic brains have reported cellular alterations in the cerebellum, a structure believed to be important in motor skills, balance, and cognition. In the posterolateral cerebellar cortex, many Purkinje cells (PCs) are missing, which are targets for afferent projection fibers from the inferior olivary nucleus in the medulla of the brainstem. The missing PCs raise an interesting question: Were the missing PCs ever produced or were they produced only to die later in migration or at their normal location between the molecular and granular layers? If they died later, then GABAergic basket cells should have formed their elaborate axonal plexuses that surround the PC body forming a nest. If the PCs were never generated then basket cell nests would not be expected. The first aim of this study was to determine whether basket cell nests have formed in areas with a decreased number of PCs leaving “empty nests”. The second aim of this study investigated whether the surviving PCs in posterolateral cerebellar cortex of individuals with autism represent a particular subpopulation of PC neurons or whether it is a more diffuse loss. The third aim investigated a major structure in the medulla of the brain stem that sends a direct projection to PCs, the inferior olivary nucleus. It was hoped that findings from these studies might allow us to understand the developmental timing of autistic behavior and might lead to the development of new early interventions that target specific neurotransmitter systems.