Abstract
BackgroundNicotine is known to differentially regulate cortical interneuron and pyramidal neuron activities in the neocortex, while the underlying molecular mechanisms have not been well studied. In this study, RNA-sequencing was performed in acutely isolated cortical somatostatin (Sst)- positive interneurons and pyramidal neurons (Thy1) from mice treated with systemic nicotine for 14 days. We assessed the differentially expressed genes (DEGs) by nicotine in Sst- or Thy1- neurons, respectively, and then compared DEGs between Sst- and Thy1- neurons in the absence and presence of nicotine.ResultsIn Sst-neurons, the DEGs by nicotine were associated with glycerophospholipid and nicotinate and nicotinamide metabolism; while in Thy1-neurons those related to immune response and purine and pyrimidine metabolisms were affected. Under basal condition, the DEGs between Sst- and Thy1- neurons were frequently associated with signal transduction, phosphorylation and potassium channel regulation. However, some new DEGs between Sst- and Thy1- neurons were found after nicotine, the majority of which belong to mitochondrial respiratory chain complex.ConclusionsNicotine differentially affected subset of genes in Sst- and Thy1- neurons, which might contribute to the distinct effect of nicotine on interneuron and pyramidal neuron activities. Meanwhile, the altered transcripts associated with mitochondrial activity were found between interneurons and pyramidal neurons after chronic nicotine.
Highlights
Nicotine is known to differentially regulate cortical interneuron and pyramidal neuron activities in the neocortex, while the underlying molecular mechanisms have not been well studied
Is this study, most Differentially expressed genes (DEG) by nicotine are not enriched in Sst- or thymus cell antigen 1 (Thy1)- neurons (FPKM
Many of the genes affected by nicotine can be categorized into pathways, still the majority of genes cannot be grouped, which does not rule out their functional importance
Summary
Nicotine is known to differentially regulate cortical interneuron and pyramidal neuron activities in the neocortex, while the underlying molecular mechanisms have not been well studied. The inter-play between interneurons and pyramidal neurons in the neocortex forms the basis of inhibition and excitation and neural network function [1, 2]. Recent studies demonstrate that GABAergic interneurons play a critical role in local circuit function and behavior [4,5,6]. Emerging evidence has shown that nicotine differentially regulates interneuron and pyramidal neuron activities. Nicotine layerspecifically regulates neuronal activities where distinct interneurons and pyramidal neurons are located [13]. Gene profiling studies have made great progress in identifying
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