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. 2021 Jan 1:396:112906.
doi: 10.1016/j.bbr.2020.112906. Epub 2020 Sep 17.

Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors

Yun-Fang Jia  1 , Katheryn Wininger  2 , Lee Peyton  1 , Ada Man-Choi Ho  3 , Doo-Sup Choi  4
Affiliations

Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors

Yun-Fang Jia et al. Behav Brain Res. .

Erratum in

Abstract

Glutamatergic dysregulation is known to contribute to obsessive-compulsive disorder (OCD). Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance. However, the role of GLT1 in OCD-like behavior remains unclear. Here, we found that astrocytic GLT1 deficient mice showed increased wheel running activity but reduced home cage activity. Notably, they exhibited elevated grooming/rearing time and increased repetitive behavior counts in contextual and cued fear conditioning. In addition, they showed increased rearing counts in the metabolic chamber, and also augmented rearing time and jumping counts in the open field test. Taken together, our findings suggest that astrocytic GLT1 deficiency promotes OCD-like repetitive behaviors.

Keywords: Fear conditioning; Glutamate transporter 1 (GLT1); Grooming; Obsessive-compulsive disorder (OCD); Repetitive behavior; Wheel running activity.

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Conflict of interest statement

Disclosures

Dr. DS Choi is a scientific advisory board member to Peptron Inc. and the Peptron had no role in the preparation, review, or approval of the manuscript; nor the decision to submit the manuscript for publication. All the other authors declare no biomedical financial interests or potential conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Prolonged activity in wheel running test in GFAPcre/+;GLT1F/F mice. (A) Activity amplitude of wheel running test in GFAPcre/+;GLT1F/F mice (n = 6) and controls (n = 4). Amplitude was measured by arbitrary unit (AU). (B) Total activity counts of wheel running test in GFAPcre/+;GLT1F/F mice (n = 5) and controls (n = 4). (C) Activity counts during active phase (dark period) of wheel running test in GFAPcre/+;GLT1F/F mice (n = 5) and controls (n = 4). (D) Activity counts during rest phase (light period) of wheel running test in GFAPcre/+;GLT1F/F mice (n = 5) and controls (n = 4). (E) Representative images of actogram for GFAPcre/+;GLT1F/F mice and control. All data are presented as mean ± SEM. Statistical significance was calculated by Student’s t-test in (B, C, and D), and by two-way repeated measures ANOVA with post hoc t-test for multiple comparisons in (A). *P < 0.05.
Fig. 2.
Fig. 2.
Lower activity in Clocklab homecage monitor test in GFAPcre/+;GLT1F/F mice. (A) Activity amplitude in home cage by Clocklab system monitor sensor assembled on the lid in GFAPcre/+;GLT1F/F mice (n = 8) and controls (n = 7). (B) Total activity counts of GFAPcre/+;GLT1F/F mice (n = 5) and controls (n = 7) in home cage. (C) Active phase activity counts (dark period) of GFAPcre/+;GLT1F/F mice (n = 7) and controls (n = 7) in home cage. (D) Rest phase activity counts (light period) of GFAPcre/+;GLT1F/F mice (n = 6) and controls (n = 6) in home cage. (E) Representative images of actogram for GFAPcre/+;GLT1F/F mice and control. All data are presented as mean±SEM. All data are presented as mean ± SEM. Statistical significance was calculated by Student’s t-test in (B, C, and D), and by two-way repeated measures ANOVA with post hoc t-test for multiple comparisons in (A). *P < 0.05.
Fig. 3.
Fig. 3.
Excessive repetitive behavior in fear memory test in GFAPcre/+;GLT1F/F mice. (A) The experimental schedule for performing fear conditioning test. (B) The grooming time during contextual test of GFAPcre/+;GLT1F/F mice (n = 8) and controls (n = 9). (C) The total counts of grooming behavior during contextual test of GFAPcre/+;GLT1F/F mice (n = 8) and controls (n = 9). (D) The total counts of syntactic chains grooming during contextual test of GFAPcre/+;GLT1F/F mice (n = 8) and controls (n = 9). (E) The total counts of rearing behavior during contextual test of GFAPcre/+;GLT1F/F mice (n = 8) and controls (n = 9). (F) The grooming time during cued test of GFAPcre/+;GLT1F/F mice (n = 10) and controls (n = 10). (G) The total counts of grooming behavior during cued test of GFAPcre/+;GLT1F/F mice (n = 10) and controls (n = 10). (H) The total counts of syntactic chains grooming during cued test of GFAPcre/+;GLT1F/F mice (n = 10) and controls (n = 10). (I) The total counts of rearing behavior during cued test of GFAPcre/+;GLT1F/F mice (n = 10) and controls (n = 10). All data are presented as mean ± SEM. Statistical significance was calculated by Student’s t-test. *P < 0.05.
Fig. 4.
Fig. 4.
Persistent behavior of GFAPcre/+;GLT1F/F mice in metabolic and open field chambers. (A) Total counts of rearing behavior for 48 h in GFAPcre/+;GLT1F/F mice (n = 3) and controls (n = 3) in the metabolic chamber. (B) Duration of rearing behavior in GFAPcre/+;GLT1F/F mice (n = 10) and controls (n = 12) in the open field test. (C) Jump counts in GFAPcre/+;GLT1F/F mice (n = 10) and controls (n = 11) in the open field test. (D) Distance moved in the open field of GFAPcre/+;GLT1F/F mice (n = 9) and controls (n = 9). All data are presented as mean±SEM. Statistical significance was calculated by Student’s t-test. *P < 0.05.
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