Figure 6.

Behavioral phenotype of mice treated with anti-NMDAR and control antibodies during weeks 3 and 4 of antibody washout. Following the infusion of anti-NMDAR and control antibodies, mice were retained in their home cages for an additional two weeks before their motor and anxiety phenotypes were assessed in an open field paradigm; the total distance traveled, and time spent in the center of the arena were recorded. Mice treated with anti-NMDAR antibodies and control antibodies displayed similar motor or anxiety phenotypes during week 3 of antibody washout (A-B). In the object location paradigm, the acquisition trial during which mice were presented with two identical objects was followed by a retention period and a test trial during which one object was displaced to a new location (NL) diagonally from the object in the familiar location (FL). The time spent in the NL and FL were recorded and the NL index was calculated as the ratio of NL and the total time spent in NL and FL. Mice exposed to anti-NMDAR antibodies demonstrated persistent loss of spatial discrimination in an object location test (C). One week later, in the Barnes maze apparatus mice were trained to locate an escape chamber situated beneath one of the peripheral holes (the target hole) over the course of three days (seven sessions). The latency to reach the target hole in the Barnes maze and the proportion of mice that did not reach the target hole (failure rate) were recorded for each training session to assess learning. During the acquisition trial, mice treated with anti-NMDAR antibodies displayed higher latencies to enter the escape chamber and higher failure rates compared to the mice treated with control antibodies demonstrating impaired learning (D-E). In a Y maze paradigm, mice were allowed to explore three open arms of the Y maze; the alternation index was calculated as a ratio of the number of alternations to the number of choices. Mice treated with anti-NMDAR antibodies demonstrated spatial memory impairment in a Y-maze paradigm (F). *, p < 0.05 (chi-squared tests); **, p < 0.01; ***, p < 0.001 (t-tests or ANOVA). The data represent mean ± SEM or proportions of animals; n = 9–10 per group. NL, new location.