Plasticity of thalamocortical axons is regulated by serotonin levels modulated by preterm birth.

Sensory inputs are conveyed to distinct primary areas of the neocortex through specific thalamocortical axons (TCA). While TCA have the ability to reorient postnatally to rescue embryonic mistargeting and target proper modality-specific areas, how this remarkable adaptive process is regulated remains largely unknown. Here, using a mutant mouse model with a shifted TCA trajectory during embryogenesis, we demonstrated that TCA rewiring occurs during a short postnatal time window, preceded by a prenatal apoptosis of thalamic neurons-two processes that together lead to the formation of properly innervated albeit reduced primary sensory areas.

Imaging the brain in action: a motorized optical rotary joint for wide field fibroscopy in freely moving animals.

Significance: The study of neuronal processes governing behavior in awake behaving mice is constantly boosted by the development of technological strategies, such as miniaturized microscopes and closed-loop virtual reality systems. However, the former limits the quality of recorded signals due to constrains in size and weight and the latter suffers from the restriction of the movement repertoire of the animal, therefore, hardly reproducing the complexity of natural multisensory scenes.

Aim: Another strategy that takes advantage of both approaches consists of the use of a fiber-bundle interface to carry optical signals from a moving animal to a conventional imaging system.

Spatiotemporal properties of whisker-evoked tactile responses in the mouse secondary somatosensory cortex.

The representation of rodents' mystacial vibrissae within the primary somatosensory (S1) cortex has become a major model for studying the cortical processing of tactile sensory information. However, upon vibrissal stimulation, tactile information first reaches S1 but also, almost simultaneously, the secondary somatosensory cortex (S2). To further understand the role of S2 in the processing of whisker inputs, it is essential to characterize the spatio-temporal properties of whisker-evoked response dynamics in this area.

Biphasic Impact of Prenatal Inflammation and Macrophage Depletion on the Wiring of Neocortical Inhibitory Circuits.

The etiology of neurodevelopmental disorders is linked to defects in parvalbumin (PV)-expressing cortical interneurons and to prenatal immune challenges. Mouse models of maternal immune activation (MIA) and microglia deficits increase the postnatal density of PV interneurons, raising the question of their functional integration. Here, we show that MIA and embryonic depletion of macrophages including microglia have a two-step impact on PV interneurons wiring onto their excitatory target neurons in the barrel cortex.

Supra-barrel Distribution of Directional Tuning for Global Motion in the Mouse Somatosensory Cortex.

Rodents explore their environment with an array of whiskers, inducing complex patterns of whisker deflections. Cortical neuronal networks can extract global properties of tactile scenes. In the primary somatosensory cortex, the information relative to the global direction of a spatiotemporal sequence of whisker deflections can be extracted at the single neuron level.

Representation of tactile scenes in the rodent barrel cortex.

After half a century of research, the sensory features coded by neurons of the rodent barrel cortex remain poorly understood. Still, views of the sensory representation of whisker information are increasingly shifting from a labeled line representation of single-whisker deflections to a selectivity for specific elements of the complex statistics of the multi-whisker deflection patterns that take place during spontaneous rodent behavior - so called natural tactile scenes. Here we review the current knowledge regarding the coding of patterns of whisker stimuli by barrel cortex neurons, from responses to single-whisker deflections to the representation of complex tactile scenes.

Review: How do spontaneous and sensory-evoked activities interact?

Twenty years ago, the seminal work of Grinvald et al. revolutionized the view cast on spontaneous cortical activity by showing how, instead of being a mere measure of noise, it profoundly impacts cortical responses to a sensory input and therefore could play a role in sensory processing. This paved the way for a number of studies on the interactions between spontaneous and sensory-evoked activities.

Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity.

Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components.

Spatially Structured Sparse Morphological Component Separation for voltage-sensitive dye optical imaging.

Background: Voltage-sensitive dye optical imaging is a promising technique for studying in vivo neural assemblies dynamics where functional clustering can be visualized in the imaging plane. Its practical potential is however limited by many artifacts.

New Method: We present a novel method, that we call "SMCS" (Spatially Structured Sparse Morphological Component Separation), to separate the relevant biological signal from noise and artifacts.

An automated workflow for the anatomo-functional mapping of the barrel cortex.

Background: The rodent barrel cortex is a widely used model to study the cortical processing of tactile sensory information. It is notable by the cytoarchitecture of its layer IV, which contains distinguishable structural units called barrels that can be considered as anatomical landmarks of the functional columnar organization of the cerebral cortex. To study sensory integration in the barrel cortex it is therefore essential to map recorded functional data onto the underlying barrel topography, which can be reconstructed from the post hoc alignment of tangential brain slices stained for cytochrome oxidase.

Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1(-/y) mice.

Hypersensitivity in response to sensory stimuli and neocortical hyperexcitability are prominent features of Fragile X Syndrome (FXS) and autism spectrum disorders, but little is known about the dendritic mechanisms underlying these phenomena. We found that the primary somatosensory neocortex (S1) was hyperexcited in response to tactile sensory stimulation in Fmr1(-/y) mice. This correlated with neuronal and dendritic hyperexcitability of S1 pyramidal neurons, which affect all major aspects of neuronal computation, from the integration of synaptic input to the generation of action potential output.

Activation of cortical 5-HT(3) receptor-expressing interneurons induces NO mediated vasodilatations and NPY mediated vasoconstrictions.

GABAergic interneurons are local integrators of cortical activity that have been reported to be involved in the control of cerebral blood flow (CBF) through their ability to produce vasoactive molecules and their rich innervation of neighboring blood vessels. They form a highly diverse population among which the serotonin 5-hydroxytryptamine 3A receptor (5-HT(3A))-expressing interneurons share a common developmental origin, in addition to the responsiveness to serotonergic ascending pathway. We have recently shown that these neurons regroup two distinct subpopulations within the somatosensory cortex: Neuropeptide Y (NPY)-expressing interneurons, displaying morphological properties similar to those of neurogliaform cells and Vasoactive Intestinal Peptide (VIP)-expressing bipolar/bitufted interneurons.

Neurotransmitter release at the thalamocortical synapse instructs barrel formation but not axon patterning in the somatosensory cortex.

To assess the impact of synaptic neurotransmitter release on neural circuit development, we analyzed barrel cortex formation after thalamic or cortical ablation of RIM1 and RIM2 proteins, which control synaptic vesicle fusion. Thalamus-specific deletion of RIMs reduced neurotransmission efficacy by 67%. A barrelless phenotype was found with a dissociation of effects on the presynaptic and postsynaptic cellular elements of the barrel.

Serotonin 3A receptor subtype as an early and protracted marker of cortical interneuron subpopulations.

To identify neocortical neurons expressing the type 3 serotonergic receptor, here we used transgenic mice expressing the enhanced green fluorescent protein (GFP) under the control of the 5-HT(3A) promoter (5-HT(3A):GFP mice). By means of whole-cell patch-clamp recordings, biocytin labeling, and single-cell reversed-transcriptase polymerase chain reaction on acute brain slices of 5-HT(3A):GFP mice, we identified 2 populations of 5-HT(3A)-expressing interneurons within the somatosensory cortex. The first population was characterized by the frequent expression of the vasoactive intestinal peptide and a typical bipolar/bitufted morphology, whereas the second population expressed predominantly the neuropeptide Y and exhibited more complex dendritic arborizations.

Degenerative abnormalities in transgenic neocortical neuropeptide Y interneurons expressing tau-green fluorescent protein.

The introduction of a reporter gene into bacterial artificial chromosome (BAC) constructs allows a rapid identification of the cell type expressing the gene of interest. Here we used BAC transgenic mice expressing a tau-sapphire green fluorescent protein (GFP) under the transcriptional control of the neuropeptide Y (NPY) genomic sequence to characterize morphological and electrophysiological properties of NPY-GFP interneurons of the mouse juvenile primary somatosensory cortex. Electrophysiological whole-cell recordings and biocytin injections were performed to allow the morphological reconstruction of the recorded neurons in three dimensions.

Straightforward synthesis of the near-infrared fluorescent voltage-sensitive dye RH1691 and analogues thereof.

A highly straightforward synthesis of the near-infrared voltage-sensitive dye RH1691 is reported featuring two sequential anionic additions of C-nucleophilic heterocycles on a cyanine. This convergent approach led to the synthesis of four new probes, which also exhibit fluorescence in the near-infrared region.

Spatiotemporal dynamics of cortical sensorimotor integration in behaving mice.

Tactile information is actively acquired and processed in the brain through concerted interactions between movement and sensation. Somatosensory input is often the result of self-generated movement during the active touch of objects, and conversely, sensory information is used to refine motor control. There must therefore be important interactions between sensory and motor pathways, which we chose to investigate in the mouse whisker sensorimotor system.

Combined voltage and calcium epifluorescence imaging in vitro and in vivo reveals subthreshold and suprathreshold dynamics of mouse barrel cortex.

Cortical dynamics can be imaged at high spatiotemporal resolution with voltage-sensitive dyes (VSDs) and calcium-sensitive dyes (CaSDs). We combined these two imaging techniques using epifluorescence optics together with whole cell recordings to measure the spatiotemporal dynamics of activity in the mouse somatosensory barrel cortex in vitro and in the supragranular layers in vivo. The two optical signals reported distinct aspects of cortical function.

Functional CB1 receptors are broadly expressed in neocortical GABAergic and glutamatergic neurons.

The cannabinoid receptor CB1 is found in abundance in brain neurons, whereas CB2 is essentially expressed outside the brain. In the neocortex, CB1 is observed predominantly on large cholecystokinin (CCK)-expressing interneurons. However, physiological evidence suggests that functional CB1 are present on other neocortical neuronal types.

Extensive overlap of mu-opioid and nicotinic sensitivity in cortical interneurons.

We studied mu-opioid transmission in acute slices of rat neocortex using whole-cell recordings and single-cell reverse transcription-polymerase chain reaction. The mu-opioid receptor (MOR) was found in gamma-aminobutyric acidergic (GABAergic) interneurons that were either layer I cells frequently expressing neuropeptide Y or layers II-V cells expressing vasoactive intestinal peptide and enkephalin (Enk). We found that mu-opioid agonists inhibit these interneurons that are selectively excited by nicotinic agonists.

Visualizing the cortical representation of whisker touch: voltage-sensitive dye imaging in freely moving mice.

Voltage-sensitive dye imaging resolves the spatiotemporal dynamics of supragranular subthreshold cortical activity with millisecond temporal resolution and subcolumnar spatial resolution. We used a flexible fiber optic image bundle to visualize voltage-sensitive dye dynamics in the barrel cortex of freely moving mice while simultaneously filming whisker-related behavior to generate two movies matched frame-by-frame with a temporal resolution of up to 2 ms. Sensory responses evoked by passive whisker stimulation lasted longer and spread further across the barrel cortex in awake mice compared to anesthetized mice.

5-HT3 receptors mediate serotonergic fast synaptic excitation of neocortical vasoactive intestinal peptide/cholecystokinin interneurons.

Neocortical neurons expressing the serotonin 5-HT3 receptor (5-HT3R) were characterized in rat acute slices by using patch-clamp recordings combined with single-cell RT-PCR and histochemical labeling. The 5-HT3A receptor subunit was expressed selectively in a subset of GABAergic interneurons coexpressing cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). The 5-HT3B subunit was never detected, indicating that 5-HT3Rs expressed by neocortical interneurons did not contain this subunit.