The Insular Cortex Of The Mice Responds To Aversive Visceral Stimuli And Mediates Feeding Behavior Unilaterally

Feeding behavior is an instinctive response for human survival,which is regulated by a complex central mechanism.This involves not only the manipulation of homeostatic mechanisms,but also non-homeostatic regulatory systems such as reward,emotion/memory,attention,and cognition.These circuits interact with each other to control energy intake and expenditure,thus maintaining the body’s energy balance.The hypothalamus is believed to be the feeding center,sensing internal and external information and maintaining energy balance.However,in some pathological conditions such as gastrointestinal discomfort or inflammation,appetite is significantly reduced and energy balance is disrupted.Are there other brain regions that can sense harmful stimuli and manipulate the hypothalamus to cause eating disorders?The insular cortex is considered as the primary taste and visceral sensory center.the dysregulation of its activity may be an important factor in anorexia nervosa.In addition,f MRI also revealed lateral activation in the insular cortex in response to different stimuli.Human brain function laterality（asymmetry）is an important attribute for human beings as organisms to adapt to the external environment.This attribute has been confirmed by numerous of brain functional imaging data,but the internal mechanism of human brain laterality is still poorly understood.We found that pathological stimulation induced by lithium chloride（Li Cl）,Lipopolysaccharide（LPS）and cis-dichlorodiammine Platinum（II）could obviously activate glutamate neurons(a IC^{Ca MKII+})in the right anterior insular cortex,but there was no lateral effect in the young mice（3 weeks）and the old mice（15months）.Intravenous injection or i.p.injection of Li Cl the mice with subdiaphragmatic vagotamy were both induced no obvious Fos expression.Photogenetic activation（inhibition）of right a IC^{Ca MKII+}cause decreased（increased）feeding.However,photogenetic activation of the left a IC^{Ca MKII+}neurons did not inhibit the feeding behavior of hungry mice.In addition,pharmacogenetic inhibition of right a IC^{Ca MKII+}neurons effectively reversed cisplatin induced weight loss.The tracer results showed that a IC^{Ca MKII+}was projected directly into v Glu T2 positive neurons in the lateral hypothalamus.Moreover,we found that photogenetic activation of the right a IC^{Ca MKII+}neurons projected to the terminal of LH could reduce the food intake and feeding times in hungry mice.Gene expression profile sequencing and q PCR were performed with the isolated left and right a IC brain regions tissues,and some genes associated with feeding behavior were observed to be laterally expressed.This study will contribute to our understanding of the mechanisms of the human brain lateralization,provided us to assess treatment success or as a novel biomarker for early detection of feeding disorders.