neophyte32
Senior Member (Voting Rights)
Highlights
•
Grik4 overexpression in mice induces anxiety, social deficits, and amygdala output imbalance
•
Grik4 normalization in BLA restored activity in regular but not late-firing cells.
•
Grik4 dose normalization in BLA abolished anxiety, depression, and social deficits
•
Regular firing neurons are key regulators of affective disorder-related behaviors
Summary
Anxiety and depression are highly prevalent psychiatric disorders with poorly understood neural mechanisms. The amygdala, particularly its hyperactivity, is strongly implicated in anxiety. Mice overexpressing the Grik4 gene display anxiety, depression, social deficits, and disrupted amygdala excitability, inducing output circuit imbalance. To dissect the role of specific amygdala neuron populations, we created mice with extra copies of Grik4 and floxed native alleles. We normalized Grik4 dosage selectively in the basolateral amygdala (BLA) pyramidal cells via stereotaxic injection of AAV-CRE-GFP, using AAV-GFP as a control. Electrophysiological recordings from centrolateral amygdala (CeL) revealed that the normalization of Grik4 restored synaptic strength in regular but not late firing neurons. Behaviorally, this intervention reversed anxiety, depression, and social deficits, but not object recognition memory impairments. These results highlight the critical role of regular firing CeL neurons in affective disorders and suggest that targeting their activity may offer new strategies for treating anxiety and depression.
I did an RNA sequencing and it showed a huge Z-score for Grik4... I think we discussed kainate, glutamate, etc., with Paolo's recent discoveries. I found that study interesting.
•
Grik4 overexpression in mice induces anxiety, social deficits, and amygdala output imbalance
•
Grik4 normalization in BLA restored activity in regular but not late-firing cells.
•
Grik4 dose normalization in BLA abolished anxiety, depression, and social deficits
•
Regular firing neurons are key regulators of affective disorder-related behaviors
Summary
Anxiety and depression are highly prevalent psychiatric disorders with poorly understood neural mechanisms. The amygdala, particularly its hyperactivity, is strongly implicated in anxiety. Mice overexpressing the Grik4 gene display anxiety, depression, social deficits, and disrupted amygdala excitability, inducing output circuit imbalance. To dissect the role of specific amygdala neuron populations, we created mice with extra copies of Grik4 and floxed native alleles. We normalized Grik4 dosage selectively in the basolateral amygdala (BLA) pyramidal cells via stereotaxic injection of AAV-CRE-GFP, using AAV-GFP as a control. Electrophysiological recordings from centrolateral amygdala (CeL) revealed that the normalization of Grik4 restored synaptic strength in regular but not late firing neurons. Behaviorally, this intervention reversed anxiety, depression, and social deficits, but not object recognition memory impairments. These results highlight the critical role of regular firing CeL neurons in affective disorders and suggest that targeting their activity may offer new strategies for treating anxiety and depression.
Scientists reverse anxiety by fixing a tiny brain circuit
A newly identified group of amygdala neurons appears to play a central role in anxiety and social behavior. Restoring normal activity in this tiny brain circuit reversed anxiety and social deficits in mice, revealing a promising new target for future treatments.
www.sciencedaily.com
I did an RNA sequencing and it showed a huge Z-score for Grik4... I think we discussed kainate, glutamate, etc., with Paolo's recent discoveries. I found that study interesting.