Program

PO1-1-17

Removal of perineuronal nets in the deep cerebellar nuclei enhances GABAergic transmission and improves delay eyeblink conditioning

[Speaker] Moritoshi Hirono:1,2
[Co-author] Satoshi Watanabe:3, Shigenori Kawahara:4, Soichi Nagao:2,5, Yuchio Yanagawa:6, Hiroaki Misonou:1
1:Graduate School of Brain Science, Doshisha University, Japan, 2:Laboratory for Motor Learning Control, RIKEN BSI, Japan, 3:National Institute of Neuroscience, National Center of Neurology and Psychiatry, Japan, 4:Graduate School of Science and Engineering, University of Toyama, Japan, 5:Laboratory for Integrative Brain Functions, Nozomi Hospital, Japan, 6:Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Japan

Perineuronal nets (PNNs), composed mainly of chondroitin sulfate proteoglycans (CSPGs), are the extracellular matrix that surrounds cell bodies, proximal dendrites, and axon initial segments of adult CNS neurons. PNNs are known to regulate neuronal plasticity, although their physiological roles in cerebellar functions have yet to be elucidated. Here, we examined the role of PNNs in regulating GABAergic transmission of Purkinje cells (PCs) onto large glutamatergic neurons in the deep cerebellar nuclei (DCN). We degradated PNNs in acute mouse cerebellar slices by incubating them with chondroitinase ABC (ChABC), and recorded inhibitory postsynaptic currents (IPSCs) from large DCN neurons. Reduction of PNNs increased the amplitude of evoked IPSCs and reduced the paired-pulse ratio. ChABC-treatment also facilitated spontaneous IPSCs and increased the miniature IPSC frequency without changing the amplitude, suggesting that degradation of PNNs in the DCN enhances GABA release from the presynaptic terminals of PCs. Furthermore, we tested if the digestion of PNNs affects cerebellar motor learning by injecting ChABC focally to the interpositus nuclei, which is responsible for the delay eyeblink conditioning. Mice received the enzyme exhibited the conditioned response at 70% after 10 days of training, which was 20% higher than the rate in control mice. Thus, our results suggest that PNNs of the DCN suppress GABAergic transmission between PCs and large glutamatergic DCN neurons and restrict motor learning in the adult cerebellum.
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