It is often assumed that studies of neural circuits in the cerebral cortex of the mouseelucidate fundamental principles of cortical organization that apply to other species including primates.However,it is increasingly clear that significant differences incircuit organization limit the applicability of the mouse as a model system for studying principles of cortical circuit function relevant to primates.Since our understanding of cortical circuits is most advanced in visual cortex,a comparison of visual cortex in mouse and primate illustrates this point.First,it is well known that the visual cortex of the mouse lacks the orderly columnar maps of stimulus properties such as selectivity for the orientation of edges and direction of motionthat are prominent in primate visual cortex.Second,these properties originate at the level of intracortical circuits in primates,but they appear to be derived pre-cortically in the mouse.Beyond these fundamental differences in functional architecture,the level and laminar expression profile of a number of genes differs in mouse and primate neocortex,In particular,many genes with prominent expression in the superficial layers of primate cortex are absent or poorly expressed in the superficial layers of mouse neocortex.Our analysis of the neocortex of the tree shrew,Tupaiabelangeriindicates that it provides a more robust model for exploring principles of cortical circuit function relevant to primates.The functional organization of visual cortex in the tree shrew exhibits a number of similarities to that of primate including well-developed columnar maps of stimulus properties that originate in intracortical circuits.In addition,compared to the mouse,the tree shrew has a more well-developed prefrontal cortex with subdivisions that resemble those of primates.Moreover,the expression patterns of a number of genes in tree shrew neocortex resemble that seen in primate.Of particular relevance for models of psychiatric disorders,the autism-linked Neuroligin 4 gene in the tree shrew shows strong homology with the human gene and high levels of mRNA expression,unlike what is found in the mouse.These factors make the tree shrew an ideal system for exploring cortical circuits in health and disease.Development of the technology to produce transgenic tree shrews would enable the types of manipulations that are necessary to fully capitalize on this unique model system.