File:Brainsci-12-00367-g001-550.webp

English: Figure 1. Transition of the cerebellar dysfunction in the infection model. (A) In response to invaded pathogens (e.g., virus, bacteria, fungus, etc.), as the acute phase, microglia present innate immune responses and release inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, etc.), which increase the intrinsic excitability of Purkinje cells in the cerebellar cortex and modulate the presynaptic release and postsynaptic responsiveness of the excitatory synapses [30]. (B) In the transient phase or chronic phase of the infection, Purkinje cells show various disruptions of the physiological properties. In the drawing, we summarized possible dysfunctions: an impairment of the parallel-fiber’s long-term synaptic plasticity and reduced parallel-fiber innervation, excess climbing-fiber innervations, an increase in GABAergic synaptic transmission, loss of Ca2+ homeostasis of Purkinje cells, hypoexcitability and aberrant oscillation, mitochondrial dysfunction, degeneration and loss of Purkinje cells, resultant reduction in the inhibitory input to deep cerebellar nuclei (DCN) neurons, and hyperexcitability of DCN neurons. (C) Aberrant Purkinje-cell activity and impairment of error modification cause the excess DCN activity, forwarding it to the efferent cerebellar pathways that contribute to the generation of tremor/ataxia.