This study provides important insights into how a specific brain region controls innate responses to odors, showing that different parts of this region govern behaviors related to attraction and aversion. The findings are convincing and supported by a combination of well-executed experimental approaches, including genetic manipulations and neural activity mapping, though the evidence could be strengthened by addressing certain methodological concerns, such as clarifying the rationale for specific experimental choices and exploring alternative techniques.
During the peer-review process the editor and reviewers write an eLife assessment that summarises the significance of the findings reported in the article on a scale ranging from landmark to useful and the strength of the evidence on a scale ranging from exceptional to inadequate. Learn more about eLife assessments. Animals exhibit innate behaviors that are stereotyped responses to specific evolutionarily relevant stimuli in the absence of prior learning or experience. These behaviors can be reduced to an axis of valence, whereby specific odors evoke approach or avoidance responses.
The posterolateral cortical amygdala plCoA mediates innate attraction and aversion to odor. However, little is known about how this brain area gives rise to behaviors of opposing motivational valence. Here, we sought to define the circuit features of plCoA that give rise to innate attraction and aversion to odor. We characterized the physiology, gene expression, and projections of this structure, identifying a divergent, topographic organization that selectively controls innate attraction and avoidance to odor.
First, we examined odor-evoked responses in these areas and found sparse encoding of odor identity, but not valence. We next considered a topographic organization and found that optogenetic stimulation of the anterior and posterior domains of plCoA elicits attraction and avoidance, respectively, suggesting a functional axis for valence. Using single cell and spatial RNA sequencing, we identified the molecular cell types in plCoA, revealing an anteroposterior gradient in cell types, whereby anterior glutamatergic neurons preferentially express VGluT2 and posterior neurons express VGluT1.
Activation of these respective cell types recapitulates appetitive and aversive behaviors, and chemogenetic inhibition reveals partial necessity for responses to innate appetitive or aversive odors. Finally, we identified topographically organized circuits defined by projections, whereby anterior neurons preferentially project to medial amygdala, and posterior neurons preferentially project to nucleus accumbens, which are respectively sufficient and necessary for innate attraction and aversion.
