Fig. 2.

CREB activation in HIPP cells during background context conditioning. a Lentiviral vector constructs for the conditional expression of control (HA), native CREB and dominant negative CREB^S133A. b Schematic of the viral transduction and behavioral testing paradigm. c CREB^S133A (n = 8) increases fear memory to the background context, while the fear response to the CS remains unaltered (controls n = 10). d The overexpression of native CREB in SST-Cre^ERT2 mice increases, whereas dominant negative CREB^S133A reduces NPY mRNA levels in the hilus (n = 6 each). GAD67 mRNA is also increased by CREB overexpression. SST mRNA by contrast is increased in the CREB^S133A group with a non-significant trend for native CREB, indicative of a phosphorylation-independent constitutive expression regulation. Note the inverted scaling of the ordinate, the lower values indicate higher expression. e A representative microscopic image shows the lentiviral expression in the hilus. Green, HA; blue, DAPI. Scale bar, 10 μm. For an overview, please see Supplementary Fig. 4c. f A schematic of the proposed circuit and the site of CREB manipulation. g The proportion of pCREB^S133/GFP double positive cells in the hilus of NPY-GFP transgenic mice is selectively increased 1 h after background context conditioning (n = 6 each). h Representative microscopic images show phosphorylated CREB expression in the hilus and granule cell layer of the DG. Arrows, pCREB^S133/GFP double-labeled cells. Scale bar, 25 μm. Data are means + s.e.m. Statistical analysis was done with Student’s unpaired t-test in c, and by Fisher’s LSD following one-way ANOVA in d and g. *P < 0.05; **P < 0.01; ***P < 0.001