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microRNA Deficiency in VIP+ Interneurons Leads to Cortical Circuit Dysfunction
Fang Qiu1, Xingfeng Mao2, Penglai Liu2
1Department of Neurology, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cerebral Cortex (New York, N.Y. : 1991)
|March 6, 2021
Summary
MicroRNAs (miRNAs) are crucial for the survival and function of vasoactive intestinal peptide (VIP+) interneurons in the brain. Removing miRNAs impairs VIP+ interneurons, affecting cortical circuits and improving spatial memory in mice.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are vital for the development and function of various cortical interneuron subtypes.
- The specific roles of miRNAs in vasoactive intestinal peptide-expressing (VIP+) interneurons, originating from the caudal ganglionic eminence, are not well understood.
- Previous research indicates miRNAs are essential for medial ganglionic eminence-derived interneuron migration, maturation, and survival.
Purpose of the Study:
- To investigate the function and necessity of miRNA biogenesis in postmitotic VIP+ interneurons.
- To elucidate the impact of miRNA deficiency on VIP+ interneuron properties and cortical circuit activity.
- To determine the behavioral consequences of impaired miRNA function in VIP+ interneurons.
Main Methods:
- Conditional deletion of Dicer, an enzyme critical for miRNA biogenesis, in postmitotic VIP+ interneurons of mice.
- Assessment of intrinsic and synaptic properties of VIP+ interneurons and pyramidal neurons.
- In vivo electrophysiological recordings of cortical local field potentials.
- Evaluation of lifespan, spatial working memory, and motor coordination in mutant mice.
Main Results:
- Conditional Dicer removal led to concordant alterations in the intrinsic and synaptic properties of VIP+ interneurons and pyramidal neurons.
- A progressive loss of VIP+ interneurons was observed in mutant mice.
- Elevated cortical local field potential power and a shortened lifespan were noted in mutant mice.
- Mutant mice demonstrated enhanced spatial working memory and motor coordination.
Conclusions:
- MicroRNAs are indispensable for the proper function and survival of VIP+ interneurons.
- VIP+ interneurons play a critical role in regulating cortical circuit activity and cognitive functions.
- Disruption of miRNA biogenesis in VIP+ interneurons has complex effects on brain function and behavior.
