a, Immunoblot (IB) analysis of Ube3a in tissue from young (P26) WT, Ube3a^m+/p-, and Ube3a^m−/p+ mice. b, Immunohistochemical analysis of Ube3a expression in the visual cortex from young (P24) WT and Ube3a^m−/p+ mice. Strong Ube3a immunoreactivity was observed in layer 2/3 (L2/3) neurons of WT mice. NeuN antibody stains cell bodies of neurons. Scale bars, 50 μm. c, Representative traces of mEPSCs recorded in L2/3 pyramidal neurons from WT (upper) or Ube3a^m−/p+ (lower) mice at ∼P10, ∼P25, and ∼P100. Scale bars, 0.2 sec, 20 pA. d, Average mEPSC amplitude as a function of postnatal age in WT (P10, n = 11 cells; P25, n =11 cells; P100, n =12 cells) and Ube3a^m−/p+ mice (P10, n =11 cells; P25, n =12 cells; P100, n =12 cells). e, Average mEPSC frequency as a function of postnatal age in WT and Ube3a^m−/p+. * p < 0.05, ** p < 0.005. Error bars in this and all subsequent figures represent s.e.m.

a, Schematic for the rearing conditions. Normally-reared (NR) animals were maintained in a 12 h consecutive dark:light cycle, and dark-reared (DR) animals were kept in complete darkness from ∼P10. b, Representative traces of mEPSCs recorded in layer 2/3 pyramidal neurons in young WT (left) or Ube3a^m−/p+ (right) mice reared in complete darkness (DR) or normally (NR). Scale bar: 0.2 sec, 20 pA. c, Dark-rearing does not affect mEPSC amplitude in WT (DR, n = 12 cells; NR, n = 11 cells) or Ube3a^m−/p+ mice (DR, n = 14 cells; NR, n = 12 cells). d, Dark-rearing significantly reduces mEPSC frequency in WT mice, but does not affect mEPSC frequency in Ube3a^m−/p+ mice. e, Representative images of basal dendrites of layer 2/3 pyramidal neurons visualized with Golgi staining. Scale bar, 10 μm. f, Average density of dendritic spines in DR (WT, n = 25 cells; Ube3a^m−/p+, n = 25 cells) and in NR (WT, n = 33 cells; Ube3a^m−/p+, n = 32 cells). *** p < 0.0005.

a, Schematic diagram of stimulating (S) and recording (R) configuration. b, Baseline synaptic responses of WT (open circle) and Ube3a^m−/p+ (closed triangle) mice were measured before and after application of conditioning stimuli to the layer 4 (L4) to L2/3 pathway of the visual cortex. Top traces are representative averaged traces of 15 min baseline (1), 30-45 min period after LTD induction (2), and their overlays (1, 2). Scale bars: 10 ms, 1 mV. The bottom graph describes average change in field EPSP (% fEPSP) upon delivery of a 1 Hz stimulus (indicated by the bar). Whereas 1 Hz stimulation for 15 min induced LTD in young WT mice, it did not change fEPSP amplitudes in Ube3a^m−/p+ mice (Percentage field excitatory postsynaptic potential (fEPSP): WT, n = 13 slices; Ube3a^m−/p+, n = 7 slices; p < 0.04). c, Same as b, except that a stimulus consisting of three 40 Hz trains was delivered (indicated by an arrow). While this stimulation induced LTP in WT mice, it did not alter fEPSP amplitudes in Ube3a^m−/p+ mice (WT, n = 12 slices; Ube3a^m−/p+, n = 10 slices; p < 0.02). d, Same as c, except that the stimulus consisted of two 100 Hz trains (indicated by an arrow). This stimulation induced LTP in both genotypes (WT, n = 12 slices; Ube3a^m−/p+, n = 10 slices; p = 0.59). e, Frequency-response functions derived from visual cortex of WT and Ube3a^m−/p+ mice. Data points represent percent changes in fEPSP 30-45 min after the delivery of conditioning stimuli. The data points for 0.033 Hz are inferred from baseline stimulation delivered once every 30 sec, which induced no obvious synaptic modifications.

a, Schematic of the recording configuration. b, Schematic for the dark-rearing condition. c, Representative waveforms and averaged data demonstrating that the level of LTP induced with 40 Hz stimulation is comparable between WT (n = 18) and Ube3a^m−/p+ (n = 18) mice reared in complete darkness (p = 0.91). Scale bars: 10 ms, 0.5 mV. d, The level of LTD is also comparable between WT and Ube3a^m−/p+ dark-reared mice (WT, n = 16 slices; Ube3a^m−/p+, n = 17 slices; p = 0.69). e, Schematic showing the schedule for exposing dark-reared mice to light. f, One day of normal-rearing following dark-rearing attenuates LTD in visual cortical slices from Ube3a^m−/p+ mice (WT, n = 19; Ube3a^m−/p+, n = 15; p = 0.08). g, Four days of normal-rearing following dark-rearing completely suppresses LTD in visual cortical slices from Ube3a^m−/p+ mice (WT, n = 9; Ube3a^m−/p+, n = 6; p < 0.01). h, Visual experience dampens LTD in the visual cortex of Ube3a^m−/p+ mice. Data represent means ± SEM of the percent reduction in fEPSP 30-45 min after the delivery of conditioning stimuli measured in normally-reared (NR), dark-reared (DR), and dark-then-light exposed for 1 or 4 days (DR+1L, DR+4L) mice.

a, Schematic of the recording configuration. b, Schematic for the late-onset visual deprivation (LOVD) rearing condition. c, Averaged data demonstrating that LTD is abolished in normally reared (NR) WT mice at ∼P40, while LTD of a similar magnitude was induced after LOVD in WT and Ube3a^m−/p+ mice (% fEPSP: NR WT, n = 10 slices; LOVD WT, n = 10 slices; LOVD Ube3a^m−/p+, n = 11 slices; p < 0.05, NR WT is significantly different from both LOVD WT and LOVD Ube3a^m−/p+, one-way ANOVA followed by Tukey). d, Bar graph of data shown in c.

a, Schedule of the surgery and recording. b, Changes in the ratio of contralateral to ipsilateral eye responses (C/I ratio) in MD (n = 13 mice) and non-deprived control WT mice (n = 14 mice) from P27 (Day 0) to P30 (Day 3). After 3 days of MD, the C/I ratio was significantly reduced (paired t-test p < 0.01), whereas this reduction was not observed in age-matched non-deprived controls (paired t-test p = 0.14). c, C/I ratios in Ube3a^m−/p+ mice (MD = 11 mice, control = 9 mice). MD did not affect the C/I ratio (paired t-test p = 0.52). C/I ratio was stable for 3 days in age-matched non-deprived controls (paired t-test p = 0.53). d, MD-induced changes in contralateral but not ipsilateral VEPs in WT mice. Top traces are representative waveforms of VEPs recorded in WT mice. Scale bars: 50 μV, 50 msec. The bottom graph describes comparisons of VEP amplitudes between control and monocularly deprived WT mice (* p < 0.05). e, Same as d except that experiments were conducted in Ube3a^m−/p+ mice.