GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation. Using a conditional ErbB4 deletion, we tested the role of vasoactive intestinal peptide (VIP)-expressing interneurons in the postnatal maturation of cortical circuits in vivo. ErbB4 removal from VIP interneurons during development leads to changes in their activity, along with severe dysregulation of cortical temporal organization and state-dependence. These alterations emerge during adolescence, and mature animals in which VIP interneurons lack ErbB4 exhibit reduced cortical responses to sensory stimuli and impaired sensory learning. Our data support a key role for VIP interneurons in cortical circuit development and suggest a possible contribution to pathophysiology in neurodevelopmental disorders. These findings provide a new perspective on the role of GABAergic interneuron diversity in cortical development.

Across sensory areas, neural microcircuits consolidate diverse streams of information into unified, representations of the external world. In the carnivore visual cortex, where eye-specific inputs converge, it has been posited that a single, shared columnar representation of orientation develops independent of sensory experience. In this study, in vivo calcium imaging with columnar and cellular resolution reveals a strikingly different developmental process in ferret visual cortex, starting with an early developmental period in which contralateral, ipsilateral or binocular stimulation each yield distinct well-organized representations of orientation that are misaligned at the columnar and cellular scale. Experience-dependent processes drive the reorganization of these three representations towards a single binocularly-aligned representation resembling the early binocular representation through concerted shifts in the preferred orientation of individual neurons. Thus, contrary to previous findings, a unified binocular representation of orientation results from an experience-dependent process that aligns the activity patterns of three distinct neural representations..

Two-photon microscopy can resolve fluorescence dynamics deep in scattering tissue, but applying this technique in vivo is limited by short working distance water-immersion objectives. Here we present an ultra long working distance (20 mm) air objective called the Cousa objective. It is optimized for performance across multiphoton imaging wavelengths, offers a >4 mm^2 FOV with submicron lateral resolution, and is compatible with commonly used multiphoton imaging systems. We share the full optical prescription, along with data on real world performance including in vivo calcium imaging in a range of species and approaches.

The visual cortex of carnivores and primates displays a high degree of modular network organization characterized by local clustering and structured long-range correlations of activity and functional properties. Excitatory networks display modular organization before the onset of sensory experience, but the developmental timeline for modular networks of GABAergic interneurons remains under-explored. Using in vivo calcium imaging of the ferret visual cortex, we find evidence that before visual experience, interneurons display weak orientation tuning and widespread, correlated activity in response to visual stimuli. Robust modular organization and orientation tuning are evident with as little as one week of visual experience. Furthermore, we find that the maturation of orientation tuning requires visual experience, while the reduction in widespread, correlated network activity does not. Thus, the maturation of inhibitory cortical networks occurs in a delayed, parallel process relative to excitatory neurons.

GABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage‐gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2‐photon calcium imaging and focal GABA uncaging, we show that voltage‐gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back‐propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage‐dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity‐dependent regulation of GABAergic inhibition.