Functional Outcomes of Cerebellar Malformations

Abstract

The cerebellum is well-established as a primary center for controlling sensorimotor functions. However, recent experiments have demonstrated additional roles for the cerebellum in higher-order cognitive functions such as language, emotion, reward, social behavior, and working memory. Based on the diversity of behaviors that it can influence, it is therefore not surprising that cerebellar dysfunction is linked to motor diseases such as ataxia, dystonia, tremor, and Parkinson’s disease as well to non-motor disorders including autism spectrum disorders (ASD), schizophrenia, depression, and anxiety. Regardless of the condition, there is a growing consensus that developmental disturbances of the cerebellum may be a central culprit in triggering a number of distinct pathophysiological processes. Here, we consider how cerebellar malformations and neuronal circuit wiring impact brain function and behavior during development. We use the cerebellum as a model to discuss the expanding view that local integrated brain circuits function within the context of distributed global networks to communicate the computations that drive complex behavior. We highlight growing concerns that neurological and neuropsychiatric diseases with severe behavioral outcomes originate from developmental insults to the cerebellum.

Long-term persistence of infectious Zika virus: Inflammation and behavioral sequela in mice

“…Therefore, although animals that survived neonatal ZIKV infection with PRVABC059 do not exhibit overt microcephaly, they do have reduced cerebellar volume and increased cerebellar fluid. Importantly, multiple studies have shown that defects in cerebellum can affect not only balance and coordination, but language, emotion, social behavior and working memory as well [ 25 , 26 ].…”

Abnormal Cerebellar Development in Autism Spectrum Disorders

“…Some children who have tumor resection surgery for medulloblastomas, a type of cerebellar tumor, also exhibit symptoms of CCAS [27] and some experience posterior fossa syndrome (PFS). PFS is characterized by a similar but often more severe constellation of symptoms including mutism, emotional lability, ataxia, hypotonia, and behavioral disturbances [28,29]. While the acute, severe presentation of PFS often resolves with time, children who experience PFS often suffer long-term neurocognitive impairment [30][31][32].…”

“…Cerebellar development follows a protracted developmental timeline compared to the cerebral cortex [11, 12, 28]. The first cerebellar neurons are born during mid embryogenesis, but neurogenesis and differentiation of the late-born granule cells, which are the most populous cell type in the brain, occurs during gestational weeks 20–40 in humans and postnatally in rodents (shown in Fig.…”

Downregulation of TrkC Receptors Increases Dendritic Arborization of Purkinje Cells in the Developing Cerebellum of the Opossum, Monodelphis domestica

“…The Purkinje cell is one of the largest neurons in the brain. It has a large cell body and a unique and distinguishable dendritic tree that produces a γ-aminobutyric acid (GABA) inhibitory neurotransmitter, while granule cells have a small somata and produce glutamate, an excitatory neurotransmitter (for review see Gill and Sillitoe, 2019 ). In rats, neurons of the deep nuclei and Purkinje cells are generated in the ventricular zone on embryonic day (E) 14 and E15, and granule cells proliferate from the caudal part of the ventricular zone known as the rhombic lip (Altman and Bayer, 1985a , b , c ; Hausmann et al, 1985 ).…”