The Cortical States of Wakefulness

Cortical neurons process information on a background of spontaneous, ongoing activity with distinct spatiotemporal profiles defining different cortical states. During wakefulness, cortical states alter constantly in relation to behavioral context, attentional level or general motor activity. In this review article, we will discuss our current understanding of cortical states in awake rodents, how they are controlled, their impact on sensory processing, and highlight areas for future research. A common observation in awake rodents is the rapid change in spontaneous cortical activity from high-amplitude, low-frequency (LF) fluctuations, when animals are quiet, to faster and smaller fluctuations when animals are active. This transition is typically thought of as a change in global brain state but recent work has shown variation in cortical states across regions, indicating the presence of a fine spatial scale control system. In sensory areas, the cortical state change is mediated by at least two convergent inputs, one from the thalamus and the other from cholinergic inputs in the basal forebrain. Cortical states have a major impact on the balance of activity between specific subtypes of neurons, on the synchronization between nearby neurons, as well as the functional coupling between distant cortical areas. This reorganization of the activity of cortical networks strongly affects sensory processing. Thus cortical states provide a dynamic control system for the moment-by-moment regulation of cortical processing

Multiple Two-Photon Targeted Whole-Cell Patch-Clamp Recordings From Monosynaptically Connected Neurons in vivo

Although we know a great deal about monosynaptic connectivity, transmission and integration in the mammalian nervous system from in vitro studies, very little is known in vivo. This is partly because it is technically difficult to evoke action potentials and simultaneously record small amplitude subthreshold responses in closely (<150 μm) located pairs of neurons. To address this, we have developed in vivo two-photon targeted multiple (2–4) whole-cell patch clamp recordings of nearby neurons in superficial cortical layers 1–3. Here, we describe a step-by-step guide to this approach in the anesthetized mouse primary somatosensory cortex, including: the design of the setup, surgery, preparation of pipettes, targeting and acquisition of multiple whole-cell recordings, as well as in vivo and post hoc histology. The procedure takes ~4 h from start of surgery to end of recording and allows examinations both into the electrophysiological features of unitary excitatory and inhibitory monosynaptic inputs during different brain states as well as the synaptic mechanisms of correlated neuronal activity

Scattering compensation by focus scanning holographic aberration probing (F-SHARP)

A long-standing goal in biomedical imaging, the control of light inside turbid media, requires knowledge of how the phase and amplitude of an illuminating wavefront are transformed as the electric field propagates inside a scattering sample onto a target plane. So far, it has proved challenging to non-invasively characterize the scattered optical wavefront inside a disordered medium. Here, we present a non-invasive scattering compensation method, termed F-SHARP, which allows us to measure the scattered electric-field point spread function (E-field PSF) in three dimensions. Knowledge of the phase and amplitude of the E-field PSF makes it possible to optically cancel sample turbulence. We demonstrate the imaging capabilities of this technique on a variety of samples and notably through vertebrate brains and across thinned skull in vivo

Identification of hydrated silicate minerals on Mars using MRO-CRISM: Geologic context near Nili Fossae and implications for aqueous alteration

The Noachian terrain west of the Isidis basin hosts a diverse collection of alteration minerals in rocks comprising varied geomorphic units within a 100,000 km2 region in and near the Nili Fossae. Prior investigations in this region by the Observatoire pour l'Minéralogie, l'Eau, les Glaces, et l'Activité (OMEGA) instrument on Mars Express revealed large exposures of both mafic minerals and iron magnesium phyllosilicates in stratigraphic context. Expanding on the discoveries of OMEGA, the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) aboard the Mars Reconnaissance Orbiter (MRO) has found more spatially widespread and mineralogically diverse alteration minerals than previously realized, which represent multiple aqueous environments. Using CRISM near-infrared spectral data, we detail the basis for identification of iron and magnesium smectites (including both nontronite and more Mg-rich varieties), chlorite, prehnite, serpentine, kaolinite, potassium mica (illite or muscovite), hydrated (opaline) silica, the sodium zeolite analcime, and magnesium carbonate. The detection of serpentine and analcime on Mars is reported here for the first time. We detail the geomorphic context of these minerals using data from high-resolution imagers onboard MRO in conjunction with CRISM. We find that the distribution of alteration minerals is not homogeneous; rather, they occur in provinces with distinctive assemblages of alteration minerals. Key findings are (1) a distinctive stratigraphy, in and around the Nili Fossae, of kaolinite and magnesium carbonate in bedrock units always overlying Fe/Mg smectites and (2) evidence for mineral phases and assemblages indicative of low-grade metamorphic or hydrothermal aqueous alteration in cratered terrains. The alteration minerals around the Nili Fossae are more typical of those resulting from neutral to alkaline conditions rather than acidic conditions, which appear to have dominated much of Mars. Moreover, the mineralogic diversity and geologic context of alteration minerals found in the region around the Nili Fossae indicates several episodes of aqueous activity in multiple distinct environments

Distinct transcriptional responses of mouse sensory neurons in models of human chronic pain conditions.

Background: Sensory neurons play an essential role in almost all pain conditions, and have recently been classified into distinct subsets on the basis of their transcriptomes. Here we have analysed alterations in dorsal root ganglia (DRG) gene expression using microarrays in mouse models related to human chronic pain. Methods: Six different pain models were studied in male C57BL/6J mice: (1) bone cancer pain using cancer cell injection in the intramedullary space of the femur; (2) neuropathic pain using partial sciatic nerve ligation; (3) osteoarthritis pain using mechanical joint loading; (4) chemotherapy-induced pain with oxaliplatin; (5) chronic muscle pain using hyperalgesic priming; and (6) inflammatory pain using intraplantar complete Freund's adjuvant. Microarray analyses were performed using RNA isolated from dorsal root ganglia and compared to sham/vehicle treated controls. Results: Differentially expressed genes (DEGs) were identified. Known and previously unreported genes were found to be dysregulated in each pain model. The transcriptomic profiles for each model were compared and expression profiles of DEGs within subsets of DRG neuronal populations were analysed to determine whether specific neuronal subsets could be linked to each of the pain models.  Conclusions: Each pain model exhibits a unique set of altered transcripts implying distinct cellular responses to different painful stimuli. No simple direct link between genetically distinct sets of neurons and particular pain models could be discerned

USH2A is a Meissner’s corpuscle protein necessary for normal vibration sensing in mice and humans

Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive, vibration-sensing neurons are associated with Meissner’s corpuscles in the skin. In the present study, we found that USH2A, a transmembrane protein with a very large extracellular domain, was found in terminal Schwann cells within Meissner’s corpuscles. Pathogenic USH2A mutations cause Usher’s syndrome, associated with hearing loss and visual impairment. We show that patients with biallelic pathogenic USH2A mutations also have clear and specific impairments in vibrotactile touch perception, as do mutant mice lacking USH2A. Forepaw rapidly adapting mechanoreceptors innervating Meissner’s corpuscles, recorded from Ush2a−/− mice, showed large reductions in vibration sensitivity. However, the USH2A protein was not found in sensory neurons. Thus, loss of USH2A in corpuscular end-organs reduced mechanoreceptor sensitivity as well as vibration perception. Thus, a tether-like protein is required to facilitate detection of small-amplitude vibrations essential for the perception of fine-grained tactile surfaces.The present study was funded by grants from the Deutsche Forschungsgemeinshaft (grant nos. SFB665-B6 to G.R.L., SFB1315 to J.F.A.P. and SFB1158-A01 to S.G.L.) and grants from the European Research Council (grant nos. 789128 to G.R.L. and ERC-2015-CoG-682422 to J.F.A.P.). Additional funding was from the Institute of Health Carlos III (Spanish Ministry of Science and Innovation, grant no. FIS PI16/00539 to J.M.).Peer reviewe

Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1

Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure. Loss of Cadm1 protected mice from obesity, and tract-tracing analysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from beyond the arcuate nucleus. Reducing Cadm1 expression in the hypothalamus and hippocampus promoted a negative energy balance and weight loss. These data identify essential roles for Cadm1-mediated neuronal input in weight regulation and provide insight into the central pathways contributing to human obesity.</p

Orbital Identification of Carbonate-Bearing Rocks on Mars

Geochemical models for Mars predict carbonate formation during aqueous alteration. Carbonate-bearing rocks had not previously been detected on Mars' surface, but Mars Reconnaissance Orbiter mapping reveals a regional rock layer with near-infrared spectral characteristics that are consistent with the presence of magnesium carbonate in the Nili Fossae region. The carbonate is closely associated with both phyllosilicate-bearing and olivine-rich rock units and probably formed during the Noachian or early Hesperian era from the alteration of olivine by either hydrothermal fluids or near-surface water. The presence of carbonate as well as accompanying clays suggests that waters were neutral to alkaline at the time of its formation and that acidic weathering, proposed to be characteristic of Hesperian Mars, did not destroy these carbonates and thus did not dominate all aqueous environments

Control of somatosensory cortical processing by thalamic posterior medial nucleus: A new role of thalamus in cortical function

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane- anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.This work was supported by a grant from Ministerio de Economia y Competitividad (BFU2012- 36107