CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats
- Northwestern University,Feinberg School of Medicine, United States
- York College of Pennsylvania, United States
- University of Wisconsin-Madison, United States
Figures
Figure 1 with 1 supplement
CREB expression levels are increased in CA1 neurons of both young and aged rats following stereotaxic injection of AAV-CREB vector into dorsal CA1 region.
(a) The AAV-CREB vector contained a GFP reporter. Example of a stitched 40x confocal image of GFP staining in CA1 area. SO – stratum oriens; SP – stratum pyramidale; SR – stratum radiatum. Scale bar …
Figure 1—figure supplement 1
Schematic for viral constructs.
AAV-CREB encoded the sequence for wild-type rat CREB, expressed from a chicken β-actin promoter with a CMV enhancer. The GFP reporter was downstream from an internal ribosomal entry site (IRES). The …
Figure 2
AAV-CREB ameliorates spatial memory deficits in aged animals.
(a) Performance on visible platform over eight trials (inset), and hidden platform over 4 sessions of training (five trials each session; one session per day) for young animals and aged animals that …
Figure 3 with 3 supplements
AAV-CREB results in higher CREB mRNA levels in CA1, and reduces AHP in infected aged animals.
CREB mRNA levels relative to young GFP group in a) CA1, (b) DG, and c) CA3. In both young and aged animals, AAV-CREB injected animals had more CREB mRNA in CA1 (n = 7, 7, 17, 15). This viral …
Figure 3—figure supplement 1
Aged unimpaired and impaired animals had the same amount of CREB mRNA.
Upon separating the aged GFP group into AU and AI, CREB mRNA levels were not different between AU and AI animals. Horizontal bars represent mean.
Figure 3—figure supplement 2
CREB protein levels are positively correlated with probe trial performance in aged GFP animals.
Levels of CREB protein in CA1 of aged GFP animals are correlated with % time spent in target quadrant on a probe trial run 1 hr after the last training session. Aged rats with more basal levels of …
Figure 3—figure supplement 3
Viral infection state had no effect on postburst AHP size in young CA1 pyramidal neurons, but did affect aged neurons.
(a) Peak and b) slow AHP were measured in AAV-CREB infected cells (CREB+), AAV-CREB uninfected cells (CREB−), and cells from AAV-GFP injected young animals (n = 9, 17, 13). For both measurements, no …
Figure 4
AAV-CREB ameliorates age-related spatial memory deficits on a more difficult water maze task.
(a) Performance on visible platform over eight trials (inset), and hidden platform over 4 sessions of training (three trials each session; one session per day) for young animals and aged animals …
Additional files
-
Supplementary file 1
Young peak and slow post-burst AHP amplitudes do not differ.
(a) Peak post-burst AHP amplitudes (mV) Aged CREB+ cells have smaller peak AHP’s than CREB- and GFP, but young cell types do not differ from each other. Data represent mean ± SEM. *p<0.05, **p<0.01 compared to aged CREB+. (b) Slow post-burst AHP amplitudes (mV) Aged CREB+ cells have smaller slow AHP’s than CREB- and GFP, but young cell types do not differ from each other. Data represent mean ± SEM. *p<0.05, **p<0.01 compared to aged CREB+.
- https://doi.org/10.7554/eLife.19358.010
-
Supplementary file 2
Resting membrane potential and input resistance do not vary across cell types.
(a) Resting Membrane Potential (mV) Resting membrane potential does not vary across different groups of cells. A two-way ANOVA revealed no significant effect of age (F1, 63 = 0.6078, n.s.) or of cell type (F2, 63 = 0.6122, n.s.). Data represent mean ± SEM. (b) Input Resistance (MΩ) Input resistance does not vary across different groups of cells. A two-way ANOVA revealed no significant effect of age (F1, 63 = 0.8259, n.s.) or of cell type (F2, 63 = 1.608, n.s.). Data represent mean ± SEM.
- https://doi.org/10.7554/eLife.19358.011
