Physiological needs bias perception and attention to relevant sensory cues. This process is ‘hijacked’ by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how ‘cognitive’ cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food- cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic ‘hunger neurons’ (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues.

Primates and rodents, which descended from a common ancestor around 90 million years ago 1 , exhibit profound differences in behaviour and cognitive capacity; the cellular basis for these differences is unknown. Here we use single-nucleus RNA sequencing to profile RNA expression in 188,776 individual interneurons across homologous brain regions from three primates (human, macaque and marmoset), a rodent (mouse) and a weasel (ferret). Homologous interneuron types-which were readily identified by their RNA-expression patterns-varied in abundance and RNA expression among ferrets, mice and primates, but varied less among primates. Only a modest fraction of the genes identified as 'markers' of specific interneuron subtypes in any one species had this property in another species. In the primate neocortex, dozens of genes showed spatial expression gradients among interneurons of the same type, which suggests that regional variation in cortical contexts shapes the RNA expression patterns of adult neocortical interneurons. We found that an interneuron type that was previously associated with the mouse hippocampus-the 'ivy cell', which has neurogliaform characteristics-has become abundant across the neocortex of humans, macaques and marmosets but not mice or ferrets. We also found a notable subcortical innovation: an abundant striatal interneuron type in primates that had no molecularly homologous counterpart in mice or ferrets. These interneurons expressed a unique combination of genes that encode transcription factors, receptors and neuropeptides and constituted around 30% of striatal interneurons in marmosets and humans.Vertebrate brains contain many specialized brain structures, each with its own evolutionary history. For example, the six-layer neocortex arose in mammals about 200 million years ago 2 , whereas distinct basal ganglia were already present in the last common ancestor of vertebrates more than 500 million years ago 3 .Brain evolution may often be driven by adaptive changes in cellular composition or molecular expression within conserved structures [4][5][6] . Examples of modifications to specific cell types within larger conserved brain systems include hindbrain circuits that control species-specific courtship calls in frogs 7 , the evolution of trichromatic vision in primates 8 , and neurons that have converted from motor to sensory processing to produce a new swimming behaviour in sand crabs 4 . Evolution can modify brain structures through diverse means, such as by increasing or reducing the production or survival of cells of a given type, altering the molecular and cellular properties of shared cell types, reallocating or redeploying cell types to new locations, losing a cell type 9 or inventing a new cell type (Fig. 1a).Genome and RNA sequencing (RNA-seq) analyses have allowed molecular inventories to be compared across species 10,11 , and single-cell RNA-seq now enables the detailed comparison of cell types and expression patterns between homologous brain structures 8,10,11 . A recent study compared n...