Cortical somatostatin interneuron subtypes form cell-type-specific circuits

Abstract

The cardinal classes are a useful simplification of cortical interneuron diversity, but such broad subgroupings gloss over the molecular, morphological, and circuit specificity of interneuron subtypes, most notably among the somatostatin interneuron class. Although there is evidence that this diversity is functionally relevant, the circuit implications of this diversity are unknown. To address this knowledge gap, we designed a series of genetic strategies to target the breadth of somatostatin interneuron subtypes and found that each subtype possesses a unique laminar organization and stereotyped axonal projection pattern. Using these strategies, we examined the afferent and efferent connectivity of three subtypes (two Martinotti and one non-Martinotti) and demonstrated that they possess selective connectivity with intratelecephalic or pyramidal tract neurons. Even when two subtypes targeted the same pyramidal cell type, their synaptic targeting proved selective for particular dendritic compartments. We thus provide evidence that subtypes of somatostatin interneurons form cell-type-specific cortical circuits.

Keywords: cortex; interneurons; intratelencephalic; laminar specificity; monosynaptic rabies tracing; optogenetics; pyramidal neurons; pyramidal tract; reciprocal connectivity; somatostatin; spatial transcriptomics; subtypes.