Fig. 1

Reduced activity of PNs by elevated Ca²⁺ influx and GABA release from interneuron nerve terminals in Fmr1-KO synapses. a Schematics of the cerebellar circuitry including excitatory and inhibitory inputs to a PN. b, c Representative firing activity of PNs recorded in the cell-attached mode from WT (b) and Fmr1-KO (c) cerebellar slices in the absence (control, top panels) or presence of an AMPA receptor blocker NBQX (10 μM, middle panels), or in a combination of NBQX and a GABA_A receptor blocker bicuculline (10 μM, bottom panels). d Summary of the frequency of APs from WT (black bars) and KO (green bars) PNs in the aforementioned conditions (b, c). e, f IPSCs obtained in the whole-cell mode at a holding potential of −60 mV from PNs of WT (e) and KO (f) mice in NBQX to block excitatory inputs. The same PNs are subsequently exposed to a Na⁺ channel blocker TTX (1 μM) and bicuculline (10 μM). g, h Summary of the amplitude and frequency of IPSCs recorded from the WT (black bars, n = 23) and KO (green bars, n = 18) animals in the above conditions (e, f). i, j Images of a BC filled with Alexa Fluor 594 (30 µM, red) projecting a long axon to innervate a PN (grey). Arrows indicate the boutons of the BC nerve terminal in a 3D multiphoton image. k, l Averaged intra-terminal Ca²⁺ signals (bottom panels) from 5 trials evoked by AP trains (100 Hz, 100 ms, top panels) delivered to the soma of BCs in WT (k) and KO (l) slices. m–p Summary of the amplitude (m), area integral (n), 10–90 rise time (o), and 90–10 decay time (p) of Ca²⁺ transients measured from the WT (black bars, n = 6) and KO (green bars, n = 7) nerve terminals. In this and following figures, data are represented as mean ± s.e.m. and asterisks (*) denote statistical significance (p < 0.05)