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. 2011 Sep 30;223(1):233-8.
doi: 10.1016/j.bbr.2011.04.020. Epub 2011 Apr 27.

Zinc transporter ZnT3 is involved in memory dependent on the hippocampus and perirhinal cortex

Guillaume Martel  1 , Charles Hevi, Noriko Kane-Goldsmith, Gleb P Shumyatsky
Affiliations

Zinc transporter ZnT3 is involved in memory dependent on the hippocampus and perirhinal cortex

Guillaume Martel et al. Behav Brain Res. .

Abstract

Since zinc transporter ZnT3 is localized to the hippocampus and perirhinal cortex, we used ZnT3 knockout mice (KO) to analyze the role of ZnT3 in memory and behavior dependent on these brain regions. ZnT3KO mice were normal in initial learning in the standard water maze but had difficulty finding a second platform location. The mutants showed increased social interaction but were deficient in social and object recognition memory. These data suggest that ZnT3 is involved in certain types of spatial memory and behavior dependent on the hippocampus and perirhinal cortex.

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Figures

Figure 1
Figure 1
Localization of ZnT3 protein in the hippocampus. A, There is a strong overlap (yellow) between antibodies against ZnT3 (green) and synaptophysin (red), a presynaptic marker. B, Double-labeling using anti-ZnT3 (green) and anti-MAP2a/b (red), a dendritic marker, shows no co-localization but proximity between the ZnT3- and MAP2-labeled neurons (arrows). Scale bar is 1 μm. C, ZnT3 mRNA is present in the hippocampus in WT mice (left panel) but not in KO mice (right panel).
Figure 2
Figure 2
ZnT3KO mice have normal learning in the water maze, but showed deficits in reversal learning. A, No difference was found between the genotypes (10 WT and 11 KO) in the visible platform task in the water maze (phase 1). B, Both genotypes learned similarly in the spatial memory task (phase 2). C, In the transfer task (reversal learning), both genotypes learned the new location of the platform, but ZnT3KO mice needed significantly more time to find the platform during the second day (phase 3). D and E, First trial of the second day of the transfer task. D, Mutants needed significantly more time to find the platform. E, Time spend on the former platform location during the first trial of the second day of transfer, showing that ZnT3KO mice spent significantly more time in the previous platform location. F, First trial of phase 3 analyzed as a probe trial showed that both genotypes used a spatial strategy during phase 2. G, Probe trial performed 24 h after the end of phase 3 showed that WT and KO mice used spatial strategy during phase 3. H, Representative swim paths used by KO and WT mice during each phase. Pictures on the left represent swim paths used on day 2 of phase 1 (visible platform). Pictures in the middle represent swim paths that were used on day 6 of phase 2 (spatial phase). Pictures on the right represent swim paths used during day 2 of phase 3 (reversal – transfer) when KO mice spent significantly more time finding the platform. Results are presented as mean ± SEM. *, P < 0.05; **, P < 0.01.
Figure 3
Figure 3
Contextual fear, social interaction, and object recognition are deficient in ZnT3KO mice. A, B and C, Contextual fear conditioning. A, Both genotypes (16 WT and 16 KO) had a similar rate of freezing during the acquisition phase. B, During the extinction phase, ZnT3KO mice froze less than WT littermates. Percent of freezing to the context is shown by 4 blocks of 150 s during 4 days of extinction. C, Extinction normalized to the initial freezing showed no difference in the rate of extinction between WT and KO mice. D, ZnT3KO mice (n = 9) have a significant increase in social interactions compared to WT littermates (n = 10). E, During social memory test, ZnT3KO mice failed to recognize an unfamiliar mouse from the familiar mouse compared to the control mice. F, Object recognition. During testing ZnT3KO mice (n = 11) failed to discriminate between the old object and the new object compared to control mice (n = 11). Results are presented as mean ± SEM. Results are presented as mean ± SEM. *, P < 0.05.
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