Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat
- Icahn School of Medicine at Mount Sinai, United States
- University of Haifa, Israel
- Albert Einstein College of Medicine, United States
Figures
Figure 1 with 1 supplement
Gene-targeting of the rat Shank3 gene.
(A) The top schematic shows the Shank3 protein domains [ankyrin repeats domain (ANK), a Src homology 3 (SH3) domain, a PDZ domain, and a sterile α-motif (SAM) domain] and indicates the published de …
Figure 1—figure supplement 1
The introduced mutation in rat targets exon 6 and leads to reduced overall Shank3 transcripts and to decreased levels of the full-length Shank3 and Homer proteins.
(A) Schematic based on the integrative genome browser (IGB) output from RNA sequencing (RNAseq) of a wild-type (WT) and a knockout (KO) sample, showing the mapped reads at exons 4 to 7 of the Shank3 …
Figure 2 with 1 supplement
Shank3-deficient rats exhibit deficits in social memory.
(A–B) Above each figure are schematics of the short- and long-term social discrimination (SD) paradigms. The examined adult subject is shown in white, and the juveniles are shown in black and grey. …
Figure 2—figure supplement 1
General social behaviors are unaffected in Shank3-deficient rats.
(A) Bars ± SEM show the average investigation times of simultaneously presented juvenile rat (gray bars) and object (black bars) for WT (n = 12), Shank3-Het (n = 12) and KO (n = 11) during the …
Figure 3 with 1 supplement
Shank3-deficient rats exhibit deficits in attention.
(A) Traces and clouds indicate mean percentage of trials with a correct response ± SEM (WT, n = 10; Het, n = 13; KO, n = 12) across 10 5-CSRT sessions. The right side in all panels is the cross-rat …
Figure 3—figure supplement 1
Shank3-deficient rats exhibit normal motivation for reward and task performance is at WT levels when cue durations are long.
(A) Traces and clouds show the average latency ± SEM from a correct screen touch to entry into a reward receptacle for WT (black, n = 10), Shank3 Het (blue, n = 13), or KO rats (red, n = 12) across …
Figure 4 with 1 supplement
Synaptic plasticity is impaired in Shank3-deficient rats.
(A) High-frequency stimulation (HFS, arrow)-induced long-term potentiation (LTP) at hippocampal Schaffer collateral-CA1 synapses (n = 6 rats/genotype, 1–2 slices per rat). (B) Long-term depression …
Figure 4—figure supplement 1
Basal synaptic transmission is intact in Shank3-deficient rats.
Input-output relationship at Schaffer collateral-CA1 synapses (n = 5 rats/genotype, three slices per rat). Summary data are presented as mean ± SD.
Figure 5 with 1 supplement
Oxytocin improves social memory and attentional deficits in Shank3-deficient rats.
Above each figure is a schematic depicting the sequence of oxytocin administration and behavioral testing on the long-term social discrimination (SD) paradigm (in A) or 5-CSRT task (in B). In A, the …
Figure 5—figure supplement 1
Oxytocin has no effect on social memory or attention in WT rats.
(A) Performance on the long-term social discrimination test following treatment with oxytocin or vehicle in WT rats (n = 7). Plotting conventions are identical to the bar plots in Figure 2A–B. (B) …
Figure 6 with 1 supplement
Oxytocin improves synaptic plasticity deficits in Shank3-deficient rats.
(A) Traces depict Hippocampal HFS-induced LTP (4 × 100 Hz) in WT and Shank3-deficient rats (n = 4 rats/genotype, six slices per rat). Application of 1 µM of oxytocin is indicated by the horizontal …
Figure 6—figure supplement 1
Oxytocin enhances LTP induced by a single pulse at 100 Hz in WT but not in Shank3-deficient rats.
(A) Traces show HFS-induced LTP (1 × 100 Hz) recorded from hippocampal slices in WT and Shank3-deficient rats (n = 4 rats/genotype, six slices per rat). Brain slices were treated with oxytocin (1 …
Additional files
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Supplementary file 1
Summary of all experimental and statistical results.
- https://doi.org/10.7554/eLife.18904.015
