Inhibitory synapse specificity: As neurons build circuits in the developing brain, they select not only what other neurons to connect to but also where on that neuron they will touch base. Working in mice, Favuzzi et al. found that gene expression programs that define subsets of interneurons also define where on the postsynaptic partner those interneurons prefer to build a synapse. One class of interneurons prefers to synapse onto the cell body of pyramidal neurons, another class onto the dendrites, and yet another onto the axon initial segment. Science , this issue p. 413

GABAergic activity is thought to influence developing neocortical sensory circuits. Yet the late postnatal maturation of local layer (L)4 circuits suggests alternate sources of GABAergic control in nascent thalamocortical networks. We show that a population of L5b, somatostatin (SST)-positive interneuron receives early thalamic synaptic input and, using laser-scanning photostimulation, identify an early transient circuit between these cells and L4 spiny stellates (SSNs) that disappears by the end of the L4 critical period. Sensory perturbation disrupts the transition to a local GABAergic circuit, suggesting a link between translaminar and local control of SSNs. Conditional silencing of SST+ interneurons or conversely biasing the circuit toward local inhibition by overexpression of neuregulin-1 type 1 results in an absence of early L5b GABAergic input in mutants and delayed thalamic innervation of SSNs. These data identify a role for L5b SST+ interneurons in the control of SSNs in the early postnatal neocortex.

The authors report that genetic disruption of the connectivity of CCK+ basket cells during development reveals a critical role for these interneurons in the regulation of theta oscillatory activity and in the coding of spatial information in the adult mouse hippocampus. The function of cortical GABAergic interneurons is largely determined by their integration into specific neural circuits, but the mechanisms controlling the wiring of these cells remain largely unknown. This is particularly true for a major population of basket cells that express the neuropeptide cholecystokinin (CCK). Here we found that the tyrosine kinase receptor ErbB4 was required for the normal integration into cortical circuits of basket cells expressing CCK and vesicular glutamate transporter 3 (VGlut3). The number of inhibitory synapses made by CCK+VGlut3+ basket cells and the inhibitory drive they exerted on pyramidal cells were reduced in conditional mice lacking ErbB4. Developmental disruption of the connectivity of these cells diminished the power of theta oscillations during exploratory behavior, disrupted spatial coding by place cells, and caused selective alterations in spatial learning and memory in adult mice. These results suggest that normal integration of CCK+ basket cells in cortical networks is key to support spatial coding in the hippocampus.

GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain.

We built a rig to perform patch-clamp and extracellular recordings from the same neuron in vivo. In this setup, the axes of two micromanipulators are precisely aligned and their relative position tracked in real-time, allowing us to accurately target patch-clamp recordings to neurons near an extracellular probe. We used this setup to generate a publicly-available dataset where a cortical neuron’s spiking activity is recorded in patch-clamp next to a dense CMOS Neuropixels probe. “Ground-truth” datasets of this kind are rare but valuable to the neuroscience community, as they power the development and improvement of spike-sorting and analysis algorithms, tethering them to empirical observations. In this article, we describe our approach and report exploratory and descriptive analysis on the resulting dataset. We study the detectability of patch-clamp spikes on the extracellular probe, within-unit reliability of spike features and spatiotemporal dynamics of the action potential waveform. We open discussion and collaboration on this dataset through an online repository, with a view to producing follow-up publications. Prologue: Our efforts to record from the same neuron in vivo using patch-clamp and dense extracellular probes have resulted in three outputs: a publicly-available dataset ( http://bit.ly/paired_recs ), a manuscript, and a code repository ( http://bit.ly/paired_git ). Together, these three components form the publication arising from the experiments we have performed. The role of the dataset is to be downloaded and re-used. The role of the manuscript is to describe the experimental methods through which we acquired the dataset, explain it and showcase which types of questions it can be used to address. The repository has two roles: first, promoting reproducibility and error correction. By making our analysis and figure-generation code freely-available, we wish to make our analysis procedures clear and enable the reader to reproduce our results from the raw data, alerting us to any potential mistakes. Second, the repository will form a living, dynamic and interactive component of the publication: a forum for open collaboration on this dataset. Any interested scientists can contribute to it, joining us in detailed exploration of these recordings with a view to producing follow-up publications in which they will be credited for their input. Why did we opt to publish this way? The first reason is that the very nature of the project we here describe – recording the same neuron with patch-clamp and extracellular probes – invites an open science and open source approach. This is because the primary use of this type of “ground truth” validation data is to aid the development of new sorting and analysis algorithms, as well as to benchmark and improve existing ones. The second reason is that despite being conceptually very simple, this project generated a large and complex dataset that can be tackled in many ways and used to address different types of question. Some of these questions are beyond the reach of our analytical expertise; others lie even beyond the scope of our scientific imagination. By releasing the dataset and providing a repository for scientific discussion and collaboration, we aim to maximise its scientific return to the community. Instead of having each interested research group work in isolation, we hope that by encouraging collaboration and discussion between peers we can foster synergy between them that will lead to work of greater scientific value. Although datasets like ours are exquisitely suited for such an approach, we believe this publication strategy needs to become more widely adopted in neuroscience. We were pleased to note recent publications spontaneously and independently using similar approaches ^1-4 , in what may well be evidence of convergent thinking. Perhaps the time has come for new publication and collaboration paradigms. We will elaborate on this subject during the Epilogue. For now, let us get back to electrophysiological recordings, before we begin an experiment on scientific collaboration.