The neonatal mammal faces an array of sensory stimuli when diverse neuronal types have yet to form sensory maps. How these inputs interact with intrinsic neuronal activity to facilitate circuit assembly is not well understood. By using longitudinal calcium imaging in unanesthetized mouse pups, we show that layer I (LI) interneurons, delineated by co-expression of the 5HT3a serotonin receptor (5HT3aR) and reelin (Re), display spontaneous calcium transients with the highest degree of synchrony among cell types present in the superficial barrel cortex at postnatal day 6 (P6). 5HT3aR Re interneurons are activated by whisker stimulation during this period, and sensory deprivation induces decorrelation of their activity. Moreover, attenuation of thalamic inputs through knockdown of NMDA receptors (NMDARs) in these interneurons results in expansion of whisker responses, aberrant barrel map formation, and deficits in whisker-dependent behavior. These results indicate that recruitment of specific interneuron types during development is critical for adult somatosensory function. VIDEO ABSTRACT.

Parvalbumin and somatostatin inhibitory interneurons gate information flow in discrete cortical areas that compute sensory and cognitive functions. Despite the considerable differences between areas, individual interneuron subtypes are genetically invariant and are thought to form canonical circuits regardless of which area they are embedded in. Here, we investigate whether this is achieved through selective and systematic variations in their afferent connectivity during development. To this end, we examined the development of their inputs within distinct cortical areas. We find that interneuron afferents show little evidence of being globally stereotyped. Rather, each subtype displays characteristic regional connectivity and distinct developmental dynamics by which this connectivity is achieved. Moreover, afferents dynamically regulated during development are disrupted by early sensory deprivation and in a model of fragile X syndrome. These data provide a comprehensive map of interneuron afferents across cortical areas and reveal the logic by which these circuits are established during development.

Higher-order projections to sensory cortical areas converge on layer 1 (L1), the primary site for integration of top-down information via the apical dendrites of pyramidal neurons and L1 GABAergic interneurons. Here we investigated the contribution of early thalamic inputs onto L1 interneurons for establishment of top-down connectivity in the primary visual cortex. We find that bottom-up thalamic inputs predominate during L1 development and preferentially target neurogliaform cells. We show that these projections are critical for the subsequent strengthening of top-down inputs from the anterior cingulate cortex onto L1 neurogliaform cells. Sensory deprivation or selective removal of thalamic afferents blocked this phenomenon. Although early activation of the anterior cingulate cortex resulted in premature strengthening of these top-down afferents, this was dependent on thalamic inputs. Our results demonstrate that proper establishment of top-down connectivity in the visual cortex depends critically on bottom-up inputs from the thalamus during postnatal development.