FIGURES AND TABLES
FROM:
Parallel Loss of Hippocampal LTD and Cognitive Flexibility in a Genetic Model of Hyperdopaminergia
Elise Morice, Jean-Marie Billard, Cécile Denis, Flavie Mathieu, Catalina Betancur, Jacques Epelbaum, Bruno Giros and Marika Nosten-Bertrand
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Figure 1.
DAT-KO mice exhibit enhanced LTP but impaired LTD. (a, left) Time course of mean theta-burst stimulation-induced LTP (arrow) in hippocampal slices of WT (n=7), HT (n=4), and KO (n=13) mice. (a, right) Summary histograms of the percent in fEPSP slope averaged from the last 15 min of recordings. (b, left) Time course of mean high frequency stimulation-induced LTP (arrow) in WT (n=7) and KO (n=6) mice. (b, right) Summary histograms of the percent in fEPSP slope averaged from the last 15 min of recordings. (c, left) Time course of mean low frequency stimulation-induced LTD (arrow) in WT (n=8), HT (n=5), and KO (n=9) mice. (c, right) Summary histograms of the percentage in fEPSP slope averaged from the last 15 min of recordings. The dotted line represents percentage of baseline. Values represent means
SEM (n=numbers of slices per group). *
P<0.05 and **
P<0.01.
Figure 2.
Haloperidol, but not methylphenidate, fully restores LTD in DAT-KO mice. (a, left) Time course of mean low-frequency stimulation-induced LTD (arrow) calculated from slices of WT (n=8) and KO (n=5) mice in the presence of haloperidol. (a, right) Summary histograms of the percent in fEPSP slope averaged from the last 15 min of recordings performed in the presence of haloperidol. (b, left) Time course of mean low-frequency stimulation-induced LTD (arrow) in WT (n=6) and KO (n=6) mice in the presence of methylphenidate. (b, right) Summary histograms of the percent in fEPSP slope averaged from the last 15 min of recordings performed in the presence of methylphenidate. The dotted line represents percentage of baseline. Values represent meansSEM (n=numbers of slices per group). **
P<0.01.
Figure 3.
DAT-KO mice exhibit normal spatial reference memory, but show disrupted reversal learning in the Morris watermaze. Performance of WT, HT, and KO mice during acquisition trials of the place (a) and reversal (c) learning. The results are expressed as distance traveled (cm) and proportion of successful trials. Probe trial of the place (b) and reversal learning (d). Mice were scored for the percentage of distance traveled in the four quadrants: north-east (NE), south-east (SE), south-west (SW), and north-west (NW), and for the number of annulus crossings. The targeted quadrant and platform are indicated in black. The horizontal line indicates the distance traveled using a random search strategy. Values represent meansSEM (n=8 mice per group).
Figure 4.
DAT-KO mice are severely impaired in the cued version of the Morris watermaze. (a) Performance of WT, HT, and KO mice on the spontaneous cued version. (b) Performance of WT and KO mice in the cued version with the platform kept at a fixed position. Results are expressed as mean distance traveled (top) and proportion of successful trials (bottom). Values represent meansSEM (n=5–7 mice per group).
Figure 5.
Haloperidol improves the performances of DAT-KO mice in the cued version of the Morris watermaze. (a) Total locomotor horizontal activity in WT and KO mice automatically recorded over a 2-h period after acute injection of saline or haloperidol (n=5–8 mice per group). (b) Performance of WT and KO mice in the cued version of the watermaze. Thirty minutes before each daily session, mutant mice were injected with haloperidol (0.075 mg/kg, i.p.) and WT mice received a saline injection. Results are expressed as mean distance traveled (top) and proportion of successful trials (bottom). Values represent meansSEM (n=8 mice per group).
Figure 6.
Methylphenidate does not improve the performance of DAT-KO mice in the cued version of the Morris watermaze. (a) Locomotor dose–response to administration of methylphenidate in DAT-KO mice over a 2-h period (n=5–15 mice per group). (b) Performance of the WT and KO in the cued version following methylphenidate treatment. Fifteen minutes before each daily session, mutant mice were injected with methylphenidate (80 mg/kg, i.p.), and WT mice received a saline injection. All results are expressed as mean distance traveled (top) and proportion of successful trials (bottom). Values represent meansSEM (n=8 mice per group).
