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. 2022 Mar 31;23(7):3894. doi: 10.3390/ijms23073894

Figure 4.

Figure 4

Altered excitatory/inhibitory balance in the cerebellum-inferior olive loop in ASD. Schematic representation of the main alterations described in the cerebellum-inferior olive circuit in ASD, as described in the main text. Briefly, Purkinje cells (PC) are reduced in number and show a decreased level of GAD67 mRNA expression, while molecular layer interneurons (MLI) show an increased inhibition over PC. These would likely determine a decrease in the inhibition (I) over deep cerebellar nuclei (DCN) neurons. DCN disinhibition would increase the excitatory (E) level increasing the output towards the thalamus and other brain regions. Concerning the loop with the inferior olive (IO), DCN neurons which project to this area show decreased GAD65 mRNA expression levels, thus resulting in a decreased inhibition over IO neurons, likely increasing the excitatory inputs and decreasing synchronicity. In ASD, multiple climbing fibers (CF) impinging on the same PC were described. Together with the alterations in IO activity, this anatomical abnormality likely contributes to impair the timing of PC spiking activity.