Inhibitory maturation and ocular dominance plasticity in mouse visual cortex require astrocyte CB1 receptors.

Endocannabinoids, signaling through the cannabinoid CB1 receptor (CB1R), regulate several forms of neuronal plasticity. CB1Rs in the developing primary visual cortex (V1) play a key role in the maturation of inhibitory circuits. Although CB1Rs were originally thought to reside mainly on presynaptic axon terminals, several studies have highlighted an unexpected role for astrocytic CB1Rs in endocannabinoid mediated plasticity.

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.

Thalamic regulation of ocular dominance plasticity in adult visual cortex.

Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral geniculate nucleus (dLGN) of the thalamus. How plasticity in the thalamus and cortex interact in the adult visual system is ill-understood.

Impaired Direction Selectivity in the Nucleus of the Optic Tract of Albino Mice.

Purpose: Human albinos have a low visual acuity. This is partially due to the presence of spontaneous erroneous eye movements called pendular nystagmus. This nystagmus is present in other albino vertebrates and has been hypothesized to be caused by aberrant wiring of retinal ganglion axons to the nucleus of the optic tract (NOT), a part of the accessory optic system involved in the optokinetic response to visual motion.

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.

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.

Somatostatin interneurons restrict cell recruitment to retinally driven spontaneous activity in the developing cortex.

During early development, before the eyes open, synaptic refinement of sensory networks depends on activity generated by developing neurons themselves. In the mouse visual system, retinal cells spontaneously depolarize and recruit downstream neurons to bursts of activity, where the number of recruited cells determines the resolution of synaptic retinotopic refinement. Here we show that during the second post-natal week in mouse visual cortex, somatostatin (SST)-expressing interneurons control the recruitment of cells to retinally driven spontaneous activity.

The essential role of recurrent processing for figure-ground perception in mice.

The segregation of figures from the background is an important step in visual perception. In primary visual cortex, figures evoke stronger activity than backgrounds during a delayed phase of the neuronal responses, but it is unknown how this figure-ground modulation (FGM) arises and whether it is necessary for perception. Here, we show, using optogenetic silencing in mice, that the delayed V1 response phase is necessary for figure-ground segregation.

Disruption of Critical Period Plasticity in a Mouse Model of Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a common monogenic neurodevelopmental disorder associated with physical and cognitive problems. The cognitive issues are thought to arise from increased release of the neurotransmitter GABA. Modulating the signaling pathways causing increased GABA release in a mouse model of NF1 reverts deficits in hippocampal learning.

Activity in Lateral Visual Areas Contributes to Surround Suppression in Awake Mouse V1.

Neuronal response to sensory stimuli depends on the context. The response in primary visual cortex (V1), for instance, is reduced when a stimulus is surrounded by a similar stimulus [1-3]. The source of this surround suppression is partially known.

NMNAT Proteins that Limit Wallerian Degeneration Also Regulate Critical Period Plasticity in the Visual Cortex.

Many brain regions go through critical periods of development during which plasticity is enhanced. These critical periods are associated with extensive growth and retraction of thalamocortical and intracortical axons. Here, we investigated whether a signaling pathway that is central in Wallerian axon degeneration also regulates critical period plasticity in the primary visual cortex (V1).

Visual Processing by Calretinin Expressing Inhibitory Neurons in Mouse Primary Visual Cortex.

Inhibition in the cerebral cortex is delivered by a variety of GABAergic interneurons. These cells have been categorized by their morphology, physiology, gene expression and connectivity. Many of these classes appear to be conserved across species, suggesting that the classes play specific functional roles in cortical processing.

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 GABA receptor α1 subunit.

β-Catenin in the Adult Visual Cortex Regulates NMDA-Receptor Function and Visual Responses.

The formation, plasticity and maintenance of synaptic connections is regulated by molecular and electrical signals. β-Catenin is an important protein in these events and regulates cadherin-mediated cell adhesion and the recruitment of pre- and postsynaptic proteins in an activity-dependent fashion. Mutations in the β-catenin gene can cause cognitive disability and autism, with life-long consequences.

Mitochondrial Dynamics in Visual Cortex Are Limited In Vivo and Not Affected by Axonal Structural Plasticity.

Mitochondria buffer intracellular Ca and provide energy [1]. Because synaptic structures with high Ca buffering [2-4] or energy demand [5] are often localized far away from the soma, mitochondria are actively transported to these sites [6-11]. Also, the removal and degradation of mitochondria are tightly regulated [9, 12, 13], because dysfunctional mitochondria are a source of reactive oxygen species, which can damage the cell [14].

Inhibitory interneurons in visual cortical plasticity.

For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, it is essential that these critical periods end after which learning becomes more conditional and active interaction with the environment becomes more important. How these age-dependent forms of plasticity are regulated has been studied extensively in the primary visual cortex.

Ocular dominance plasticity disrupts binocular inhibition-excitation matching in visual cortex.

Background: To ensure that neuronal networks function in a stable fashion, neurons receive balanced inhibitory and excitatory inputs. In various brain regions, this balance has been found to change temporarily during plasticity. Whether changes in inhibition have an instructive or permissive role in plasticity remains unclear.

Competition and Homeostasis of Excitatory and Inhibitory Connectivity in the Adult Mouse Visual Cortex.

During cortical development, synaptic competition regulates the formation and adjustment of neuronal connectivity. It is unknown whether synaptic competition remains active in the adult brain and how inhibitory neurons participate in this process. Using morphological and electrophysiological measurements, we show that expressing a dominant-negative form of the TrkB receptor (TrkB.

Lack of functional specialization of neurons in the mouse primary visual cortex that have expressed calretinin.

Calretinin is a calcium-binding protein often used as a marker for a subset of inhibitory interneurons in the mammalian neocortex. We studied the labeled cells in offspring from a cross of a Cre-dependent reporter line with the CR-ires-Cre mice, which express Cre-recombinase in the same pattern as calretinin. We found that in the mature visual cortex, only a minority of the cells that have expressed calretinin and Cre-recombinase during their lifetime is GABAergic and only about 20% are immunoreactive for calretinin.

Orientation-tuned surround suppression in mouse visual cortex.

The firing rates of neurons in primary visual cortex (V1) are suppressed by large stimuli, an effect known as surround suppression. In cats and monkeys, the strength of suppression is sensitive to orientation; responses to regions containing uniform orientations are more suppressed than those containing orientation contrast. This effect is thought to be important for scene segmentation, but the underlying neural mechanisms are poorly understood.

Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to mutations in the CRB1 gene.

In humans, the Crumbs homolog-1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype-phenotype correlation for CRB1 mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, we generated and analysed conditional knockout mice lacking CRB2 in the developing retina.

Elimination of inhibitory synapses is a major component of adult ocular dominance plasticity.

During development, cortical plasticity is associated with the rearrangement of excitatory connections. While these connections become more stable with age, plasticity can still be induced in the adult cortex. Here we provide evidence that structural plasticity of inhibitory synapses onto pyramidal neurons is a major component of plasticity in the adult neocortex.

Synaptotagmin-2 is a reliable marker for parvalbumin positive inhibitory boutons in the mouse visual cortex.

Background: Inhibitory innervation by parvalbumin (PV) expressing interneurons has been implicated in the onset of the sensitive period of visual plasticity. Immunohistochemical analysis of the development and plasticity of these inhibitory inputs is difficult because PV expression is low in young animals and strongly influenced by neuronal activity. Moreover, the synaptic boutons that PV neurons form onto each other cannot be distinguished from the innervated cell bodies by immunostaining for this protein because it is present throughout the cells.

Critical-period plasticity in the visual cortex.

In many regions of the developing brain, neuronal circuits undergo defined phases of enhanced plasticity, termed critical periods. Work in the rodent visual cortex has led to important insights into the cellular and molecular mechanisms regulating the timing of the critical period. Although there is little doubt that the maturation of specific inhibitory circuits plays a key role in the opening of the critical period in the visual cortex, it is less clear what puts an end to it.