TY - JOUR
T1 - Deletion of Dtnbp1 in mice impairs threat memory consolidation and is associated with enhanced inhibitory drive in the amygdala
AU - Huang, Cathy C.Y.
AU - Muszynski, Kevin J.
AU - Bolshakov, Vadim Y.
AU - Balu, Darrick T.
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Schizophrenia is a severe and highly heritable disorder. Dystrobrevin-binding protein 1 (DTNBP1), also known as dysbindin-1, has been implicated in the pathophysiology of schizophrenia. Specifically, dysbindin-1 mRNA and protein expression are decreased in the brains of subjects with this disorder. Mice lacking dysbinidn-1 also display behavioral phenotypes similar to those observed in schizophrenic patients. However, it remains unknown whether deletion of dysbindin-1 impacts functions of the amygdala, a brain region that is critical for emotional processing, which is disrupted in patients with schizophrenia. Here, we show that dysbindin-1 is expressed in both excitatory and inhibitory neurons of the basolateral amygdala (BLA). Deletion of dysbindin-1 in male mice (Dys −/− ) impaired cued and context-dependent threat memory, without changes in measures of anxiety. The behavioral deficits observed in Dys −/− mice were associated with perturbations in the BLA, including the enhancement of GABAergic inhibition of pyramidal neurons, increased numbers of parvalbumin interneurons, and morphological abnormalities of dendritic spines on pyramidal neurons. Our findings highlight an important role for dysbindin-1 in the regulation of amygdalar function and indicate that enhanced inhibition of BLA pyramidal neuron activity may contribute to the weakened threat memory expression observed in Dys −/− mice.
AB - Schizophrenia is a severe and highly heritable disorder. Dystrobrevin-binding protein 1 (DTNBP1), also known as dysbindin-1, has been implicated in the pathophysiology of schizophrenia. Specifically, dysbindin-1 mRNA and protein expression are decreased in the brains of subjects with this disorder. Mice lacking dysbinidn-1 also display behavioral phenotypes similar to those observed in schizophrenic patients. However, it remains unknown whether deletion of dysbindin-1 impacts functions of the amygdala, a brain region that is critical for emotional processing, which is disrupted in patients with schizophrenia. Here, we show that dysbindin-1 is expressed in both excitatory and inhibitory neurons of the basolateral amygdala (BLA). Deletion of dysbindin-1 in male mice (Dys −/− ) impaired cued and context-dependent threat memory, without changes in measures of anxiety. The behavioral deficits observed in Dys −/− mice were associated with perturbations in the BLA, including the enhancement of GABAergic inhibition of pyramidal neurons, increased numbers of parvalbumin interneurons, and morphological abnormalities of dendritic spines on pyramidal neurons. Our findings highlight an important role for dysbindin-1 in the regulation of amygdalar function and indicate that enhanced inhibition of BLA pyramidal neuron activity may contribute to the weakened threat memory expression observed in Dys −/− mice.
UR - http://www.scopus.com/inward/record.url?scp=85064203473&partnerID=8YFLogxK
U2 - 10.1038/s41398-019-0465-y
DO - 10.1038/s41398-019-0465-y
M3 - 期刊論文
C2 - 30967545
AN - SCOPUS:85064203473
SN - 2158-3188
VL - 9
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 132
ER -