Potential impact of perineuronal net on the pathogenesis of SchizophreniaToshitaka Oohashiin the cerebellum (Figure 1)9).The principal cells of the MNTB receive their large single input, which is known as calyx of Held, from the ventral cochlea nucleus. MNTB neurons are enclosed in densely organized extracellular matrix structures, known as PNN. We have recently reported that HAPLN4 is important for brevican localization specific at the perisynaptic space between the calyx of Held terminals and principal neurons10). Genetic deletion of Hapln4 exhibited a clear ectopic shift of brevican localization from the perisynaptic space between the calyx of Held terminals and principal neurons to the neuropil surrounding the whole calyx Figure 1. HAPLN4 is a PNN component that selectively contributes to formation and transmission of PC-DCN synapses in the cerebellum9)Figure 2. Patch-clamp techniques application to rodent calyx of Held – MNTB synapses for electrophysiological studies11) (A) and morphological studies (A photo courtesy of Dr. Tetsuya Hori) (B).of Held terminals. In contrast, aggrecan expression showed a consistent localization at the surrounding neuropil, together with HAPLN1 and tenascin-R, in both KO and wild-type mice. To elucidate the functional role during postnatal development, we have investigated the electrophysiological properties of calyx-MNTB synapses in Hapln4-KO mice. The advantage of calyx-MNTB synapses is the availability of paired whole-cell presynaptic and postsynaptic recordings (Figure 2A). Presynaptic currents are recorded from a calyceal terminal (left patch pipette in A), while postsynaptic currents are recorded from a principal neuron in the MNTB (right pipette in A). After recording, loading fluorophore from the presynaptic whole-cell 72
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