The prefrontal cortex(PFC)is thought to be involved in higher order cognitive functions,such as in working memory,abstract categorization,and reward processing.It has been reported that two distinct neuron classes(put...The prefrontal cortex(PFC)is thought to be involved in higher order cognitive functions,such as in working memory,abstract categorization,and reward processing.It has been reported that two distinct neuron classes(putative pyramidal cells and interneurons)in the PFC played different functional roles in neural circuits involved in forming working memory and abstract categories.However,it remains elusive how the two types of neurons process reward information in the PFC.To investigate this issue,the activity of single neurons was extracellularly recorded in the PFC of the monkey performing a reward predicting task.PFC neurons were classified into putative pyramidal cells and interneurons,respectively,based on the waveforms of action potentials.Both the two types of neurons encoded reward information and discriminated two reward conditions(the preferred reward condition vs.the nonpreferred reward condition).However,the putative pyramidal neurons had better and more reliable discriminability than the putative interneurons.Also,the pyramidal cells represented reward information in the preferred reward condition,but not in the nonpreferred reward condition by raising their firing rates relative to the baseline rates.In contrast,the interneurons encoded reward information in the nonpreferred reward condition,but not in the preferred reward condition by inhibiting their discharge rates relative to the baseline rates.These results suggested that the putative pyramidal cells and interneurons had complementary functions in reward processing.These findings may help to clarify individual functions of each type of neurons in PFC neuronal circuits involved in reward processing.展开更多
Dystrobrevin-binding protein 1 （Dtnbp1） is one of the earliest identified schizophrenia susceptibility genes. Reduced expression of DTNBP1 is commonly found in brain areas of schizophrenic patients. Dtnbp1-nuU mutan...Dystrobrevin-binding protein 1 （Dtnbp1） is one of the earliest identified schizophrenia susceptibility genes. Reduced expression of DTNBP1 is commonly found in brain areas of schizophrenic patients. Dtnbp1-nuU mutant mice exhibit abnormalities in beha- viors and impairments in neuronal activities. However, how diminished DTNBP1 expression contributes to clinical relevant fea- tures of schizophrenia remains to be illustrated. Here, using a conditional Dtnbp1 knockout mouse line, we identified an in vivo schizophrenia-relevant function of DTNBP1 in pyramidal neurons of the medial prefrontal cortex （mPFC）. We demonstrated that DTNBP1 elimination specifically in pyramidal neurons of the mPFC impaired mouse pre-pu[se inhibition （PPI） behavior and reduced perisomatic GABAergic synapses. We further revealed that loss of DTNBP1 in pyramidal neurons diminished activity- dependent secretion of brain-derived neurotrophic factor （BDNF）. Finally, we showed that chronic BDNF infusion in the mPFC fully rescued both GABAergic synaptic dysfunction and PPI behavioral deficit induced by DTNBP1 elimination from pyramidal neurons. Our findings highlight brain region- and cell type-specific functions of DTNBP1 in the pathogenesis of schizophrenia, and under- score BDNF restoration as a potential therapeutic strategy for schizophrenia.展开更多
基金supported by Grant-in-aid for Scientific Research on Innovative Areas,Grant-in-aid for Scientific Research(A),and Tamagawa Global Center of Excellence,Japanthe National Natural Science Foundation of China(Grant No.11232005)+1 种基金the Fundamental Research Funds for the Central Universities of ChinaShanghai Pujiang Program(Grant No.13PJ1402000)
文摘The prefrontal cortex(PFC)is thought to be involved in higher order cognitive functions,such as in working memory,abstract categorization,and reward processing.It has been reported that two distinct neuron classes(putative pyramidal cells and interneurons)in the PFC played different functional roles in neural circuits involved in forming working memory and abstract categories.However,it remains elusive how the two types of neurons process reward information in the PFC.To investigate this issue,the activity of single neurons was extracellularly recorded in the PFC of the monkey performing a reward predicting task.PFC neurons were classified into putative pyramidal cells and interneurons,respectively,based on the waveforms of action potentials.Both the two types of neurons encoded reward information and discriminated two reward conditions(the preferred reward condition vs.the nonpreferred reward condition).However,the putative pyramidal neurons had better and more reliable discriminability than the putative interneurons.Also,the pyramidal cells represented reward information in the preferred reward condition,but not in the nonpreferred reward condition by raising their firing rates relative to the baseline rates.In contrast,the interneurons encoded reward information in the nonpreferred reward condition,but not in the preferred reward condition by inhibiting their discharge rates relative to the baseline rates.These results suggested that the putative pyramidal cells and interneurons had complementary functions in reward processing.These findings may help to clarify individual functions of each type of neurons in PFC neuronal circuits involved in reward processing.
文摘Dystrobrevin-binding protein 1 （Dtnbp1） is one of the earliest identified schizophrenia susceptibility genes. Reduced expression of DTNBP1 is commonly found in brain areas of schizophrenic patients. Dtnbp1-nuU mutant mice exhibit abnormalities in beha- viors and impairments in neuronal activities. However, how diminished DTNBP1 expression contributes to clinical relevant fea- tures of schizophrenia remains to be illustrated. Here, using a conditional Dtnbp1 knockout mouse line, we identified an in vivo schizophrenia-relevant function of DTNBP1 in pyramidal neurons of the medial prefrontal cortex （mPFC）. We demonstrated that DTNBP1 elimination specifically in pyramidal neurons of the mPFC impaired mouse pre-pu[se inhibition （PPI） behavior and reduced perisomatic GABAergic synapses. We further revealed that loss of DTNBP1 in pyramidal neurons diminished activity- dependent secretion of brain-derived neurotrophic factor （BDNF）. Finally, we showed that chronic BDNF infusion in the mPFC fully rescued both GABAergic synaptic dysfunction and PPI behavioral deficit induced by DTNBP1 elimination from pyramidal neurons. Our findings highlight brain region- and cell type-specific functions of DTNBP1 in the pathogenesis of schizophrenia, and under- score BDNF restoration as a potential therapeutic strategy for schizophrenia.
