Loss of Smad4 Modulates Anxiety-Related Behavior in the Elevated Plus Maze.

<p>In the Elevated Plus Maze (A) the fbΔSmad4 mutant mice (blue) spent a significantly increased proportion of time exploring the open-arms, (B) had a significantly increased duration of time on the open-arms, (C) and made significantly more entries onto the open-arms compared to control littermates (white). When closed-arm exploration was examined, (D) the fbΔSmad4 mutant mice spent a significantly reduced proportion of time on the closed-arms, but (E) there was no significant difference in duration of time on the closed-arms, however, (F) the number of closed-arm entries was significantly reduced. Results reported as mean ± S.E.M. Asterisk indicates *p<0.05.</p

Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration

<div><p>To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.</p></div

Loss of BMPRII Modulates Anxiety-Related Behavior in the Elevated Plus Maze.

<p>In the Elevated Plus Maze (A) the fbΔBMPRII mutant mice (red) spent a significantly increased proportion of time exploring the open-arms compared to control littermates (white), and (B) had a significantly increased duration of time on the open-arms, (C) but there was no significant difference in open-arm entries. When closed-arm exploration was examined, (D) the fbΔBMPRII mutant mice spent a significantly reduced proportion of time on the closed-arms, and (E) had a significantly reduced duration of time on the closed-arms, (F) but there was no significant difference in closed-arm entries. Results reported as mean ± S.E.M. Asterisk indicates *p<0.05 or **p<0.005.</p

Floating Behavior in the Water Maze and Immobility of BMPRII Mice in the Porsolt Swim Test.

<p>(A) The fbΔBMPRII mutant mice (red) had significantly more trials with floating behavior during the water maze compared to control littermates, (B) and significantly more trials with floating across days, which impacted the average swimming speed of the mice, as well as the latency to find the hidden platform. (C) When tested in the PST, the fbΔBMPRII mutants did not have any differences in immobility compared to littermate controls, (D) and did not have any differences in the latency to first bout of immobility. Results reported as mean ± S.E.M. Asterisk indicates *p<0.05, **p<0.005.</p

Prepulse Inhibition of the Acoustic Startle Reflex in fbΔBMPRII Mice.

<p>The fbΔBMPRII mutants (red) and control littermates (white) showed similar levels of prepulse inhibition of the acoustic startle across three different intensities of the prepulse stimulus. Thus, the mutant mice did not show deficits in sensorimotor gating.</p

Western Blot Analysis of BMPRII Protein in the Brain.

<p>Western blot analysis of tissues from the hippocampus (HP), Cerebellum (Cb), and cortex (Cx) in BMPRII flox/flox controls (cn) and BMPRII flox/flox; CaMKIIα-Cre (ko) mice. At 2 months old, fbΔBMPRII mutant mice show a great reduction of BMPRII protein in the hippocampus and cortex, but show similar levels of BMPRII protein in the cerebellum.</p