Experience shapes chandelier cell function and structure in the visual cortex.

Detailed characterization of interneuron types in primary visual cortex (V1) has greatly contributed to understanding visual perception, yet the role of chandelier cells (ChCs) in visual processing remains poorly characterized. Using viral tracing we found that V1 ChCs predominantly receive monosynaptic input from local layer 5 pyramidal cells and higher-order cortical regions. Two-photon calcium imaging and convolutional neural network modeling revealed that ChCs are visually responsive but weakly selective for stimulus content. In mice running in a virtual tunnel, ChCs respond strongly to events known to elicit arousal, including locomotion and visuomotor mismatch. Repeated exposure of the mice to the virtual tunnel was accompanied by reduced visual responses of ChCs and structural plasticity of ChC boutons and axon initial segment length. Finally, ChCs only weakly inhibited pyramidal cells. These findings suggest that ChCs provide an arousal-related signal to layer 2/3 pyramidal cells that may modulate their activity and/or gate plasticity of their axon initial segments during behaviorally relevant events.

SpecSeg is a versatile toolbox that segments neurons and neurites in chronic calcium imaging datasets based on low-frequency cross-spectral power.

Imaging calcium signals in neurons of animals using single- or multi-photon microscopy facilitates the study of coding in large neural populations. Such experiments produce massive datasets requiring powerful methods to extract responses from hundreds of neurons. We present SpecSeg, an open-source toolbox for (1) segmentation of regions of interest (ROIs) representing neuronal structures, (2) inspection and manual editing of ROIs, (3) neuropil correction and signal extraction, and (4) matching of ROIs in sequential recordings. ROI segmentation in SpecSeg is based on temporal cross-correlations of low-frequency components derived by Fourier analysis of each pixel with its neighbors. The approach is user-friendly, intuitive, and insightful and enables ROI detection around neurons or neurites. It works for single- (miniscope) and multi-photon microscopy data, eliminating the need for separate toolboxes. SpecSeg thus provides an efficient and versatile approach for analyzing calcium responses in neuronal structures imaged over prolonged periods of time.

A parameter-free statistical test for neuronal responsiveness.

Neurophysiological studies depend on a reliable quantification of whether and when a neuron responds to stimulation. Simple methods to determine responsiveness require arbitrary parameter choices, such as binning size, while more advanced model-based methods require fitting and hyperparameter tuning. These parameter choices can change the results, which invites bad statistical practice and reduces the replicability. New recording techniques that yield increasingly large numbers of cells would benefit from a test for cell-inclusion that requires no manual curation. Here, we present the parameter-free ZETA-test, which outperforms t-tests, ANOVAs, and renewal-process-based methods by including more cells at a similar false-positive rate. We show that our procedure works across brain regions and recording techniques, including calcium imaging and Neuropixels data. Furthermore, in illustration of the method, we show in mouse visual cortex that (1) visuomotor-mismatch and spatial location are encoded by different neuronal subpopulations and (2) optogenetic stimulation of VIP cells leads to early inhibition and subsequent disinhibition.

Amblyopia: The Thalamus Is a No-Go Area for Visual Acuity.

When one eye does not function well during development, the visual cortex becomes less responsive to it and visual acuity declines. New research suggests that reduced response strength and deteriorating acuity occur in separate circuits.

Thalamic inhibition regulates critical-period plasticity in visual cortex and thalamus.

During critical periods of development, experience shapes cortical circuits, resulting in the acquisition of functions used throughout life. The classic example of critical-period plasticity is ocular dominance (OD) plasticity, which optimizes binocular vision but can reduce the responsiveness of the primary visual cortex (V1) to an eye providing low-grade visual input. The onset of the critical period of OD plasticity involves the maturation of inhibitory synapses within V1, specifically those containing the GABAA receptor α1 subunit. Here we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus (dLGN) also undergo OD plasticity. This process depends on thalamic α1-containing synapses and is required for consolidation of the OD shift in V1 during long-term deprivation. Our findings demonstrate that thalamic inhibitory circuits play a central role in the regulation of the critical period. This has far-reaching consequences for the interpretation of studies investigating the molecular and cellular mechanisms regulating critical periods of brain development.