Fig. 1: Spontaneous glutamate transmission increases in dorsolateral striatal VKI SPNs emerges by 6 months. | npj Parkinson's Disease

Fig. 1: Spontaneous glutamate transmission increases in dorsolateral striatal VKI SPNs emerges by 6 months.

From: Emergent glutamate & dopamine dysfunction in VPS35(D620N) knock-in mice and rapid reversal by LRRK2 inhibition

Fig. 1

A i) Schematic depicting whole-cell patch-clamp recording of spiny projection neurons (SPNs) in the dorsolateral striatum (STR) from acute coronal brain sections also containing cortex (CTX). ii) Representative trace of voltage-clamp recording of spontaneous excitatory post-synaptic current (sEPSC) from dorsolateral striatal SPNs. Representations of amplitude, inter-event interval, and decay tau measurements annotated in red. B At 1 month, i) cumulative probability distributions of sEPSC amplitude are not significantly different between VKI and WT SPNs (2-way ANOVA Interaction p > 0.99, genotype p = 0.22). ii) Cumulative probability distributions of inter-event intervals are not significantly different between VKI and WT SPNs (2-way ANOVA interaction p = 0.99, genotype p = 0.93). iii) sEPSC decay tau is not significantly different between VKI and WT SPNs (Unpaired t-test p = 0.43). C At 3 months, i) cumulative probability distributions show VKI SPNs have more, larger amplitude sEPSC than WT SPNs (2-way ANOVA interaction p = 0.02, genotype p = 0.21). ii) sEPSC inter-event intervals are not significantly different between genotypes (2-way ANOVA interaction p = 0.10, genotype p = 0.95). iii) Average sEPSC decay tau is significantly faster in VKI vs WT neurons (Mann-Whitney U-test p = 0.01). D At 6 months, i) cumulative distributions show a significantly higher number of larger-amplitude sEPSCs in VKI neurons (2-way ANOVA interaction p < 0.0001, genotype p = 0.02). ii) Cumulative distributions of sEPSC inter-event intervals indicate VKI neurons have shorter inter-event intervals than WT neurons (2-way ANOVA interaction p < 0.0001, genotype p = 0.06). iii) Average sEPSC decay taus are not significantly different in VKI vs WT neurons (Mann-Whitney U-test p = 0.65). Asterisks denote pairwise comparisons; * 0.05>p > 0.01, ** 0.01>p > 0.001, *** 0.001>p > 0.0001, **** p > 0.0001. 2-way ANOVA comparisons listed if p < 0.10.

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