Head movements are sensed by the vestibular organs. Unlike classical senses, signals from vestibular organs are not conveyed to a dedicated cortical area but are broadcast throughout the cortex. Surprisingly, the routes taken by vestibular signals to reach the cortex are still largely uncharted.
View Article and Find Full Text PDFProgressive supranuclear palsy (PSP) is a neurodegenerative disorder with an estimated prevalence of 5-7 people in 100,000. Clinically characterized by impairments in gait, balance, and eye movements, as well as aggregated Tau pathology, PSP leads to death in approximately 5-8 years. No disease-modifying treatments are currently available.
View Article and Find Full Text PDFChildren diagnosed with autism spectrum disorder (ASD) commonly present with sensory hypersensitivity or abnormally strong reactions to sensory stimuli. Such hypersensitivity can be overwhelming, causing high levels of distress that contribute markedly to the negative aspects of the disorder. Here, we identify a mechanism that underlies hypersensitivity in a sensorimotor reflex found to be altered in humans and in mice with loss of function in the ASD risk-factor gene SCN2A.
View Article and Find Full Text PDFSensory cortices modulate innate behaviors through corticofugal projections targeting phylogenetically-old brainstem nuclei. However, the principles behind the functional connectivity of these projections remain poorly understood. Here, we show that in mice visual cortical neurons projecting to the optic-tract and dorsal-terminal nuclei (NOT-DTN) possess distinct response properties and anatomical connectivity, supporting the adaption of an essential innate eye movement, the optokinetic reflex (OKR).
View Article and Find Full Text PDFChildren diagnosed with autism spectrum disorder (ASD) commonly present with sensory hypersensitivity, or abnormally strong reactions to sensory stimuli. Such hypersensitivity can be overwhelming, causing high levels of distress that contribute markedly to the negative aspects of the disorder. Here, we identify the mechanisms that underlie hypersensitivity in a sensorimotor reflex found to be altered in humans and in mice with loss-of-function in the ASD risk-factor gene .
View Article and Find Full Text PDFEssential oils (EOs) are increasingly consumed as food supplements. The few published recommended doses available generally lack details both on the methodology used and concentration limits for substances of concern, including genotoxic carcinogens. We propose a tiered approach based on the toxicological evaluation of maximized concentrations of each constituent present in the EO investigated.
View Article and Find Full Text PDFLong-term synaptic plasticity is believed to be the cellular substrate of learning and memory. Synaptic plasticity rules are defined by the specific complement of receptors at the synapse and the associated downstream signaling mechanisms. In young rodents, at the cerebellar synapse between granule cells (GC) and Purkinje cells (PC), bidirectional plasticity is shaped by the balance between transcellular nitric oxide (NO) driven by presynaptic -methyl-D-aspartate receptor (NMDAR) activation and postsynaptic calcium dynamics.
View Article and Find Full Text PDFThe vestibular system broadcasts head-movement-related signals to sensory areas throughout the brain, including visual cortex. These signals are crucial for the brain's ability to assess whether motion of the visual scene results from the animal's head movements. However, how head movements affect visual cortical circuits remains poorly understood.
View Article and Find Full Text PDFOrganisms must learn new strategies to adapt to changing environments. Activity in different neurons often exhibits synchronization that can dynamically enhance their communication and might create flexible brain states that facilitate changes in behavior. We studied the role of gamma-frequency (~40 Hz) synchrony between prefrontal parvalbumin (PV) interneurons in mice learning multiple new cue-reward associations.
View Article and Find Full Text PDFThe cerebellum aids the learning of fast, coordinated movements. According to current consensus, erroneously active parallel fibre synapses are depressed by complex spikes signalling movement errors. However, this theory cannot solve the of processing a global movement evaluation into multiple cell-specific error signals.
View Article and Find Full Text PDFIn the classical view, postsynaptic NMDA receptors (NMDARs) trigger Hebbian plasticity via Ca influx. However, unconventional presynaptic NMDARs (preNMDARs) which regulate both long-term and short-term plasticity at several synapse types have also been found. A lack of sufficiently specific experimental manipulations and a poor understanding of how preNMDARs signal have contributed to long-standing controversy surrounding these receptors.
View Article and Find Full Text PDFPhotodiagnosis Photodyn Ther
December 2017
Background: Pretreatment of skin to remove scales/crusts and roughen the surface is essential to enhance the penetration of topically applied methyl aminolevulinate (MAL) prior to photodynamic therapy and to permit daylight to access all parts of the skin lesions. Numerous procedures of skin preparation are currently available. This study compared the in vitro penetration of MAL into ex vivo human skin pretreated with skin preparation pad abrasion or a microneedling device, and evaluated the effectiveness of an iontophoretic device in delivering MAL into ex vivo human skin.
View Article and Find Full Text PDFBackground: Photodynamic therapy (PDT) is a successful treatment for non-melanoma skin cancers. Methyl-aminolevulinate (MAL) is metabolized to protoporphyrin IX (PpIX) which accumulates in the skin lesion and which generates a painful photochemical toxic reaction upon red light exposure. PDT using daylight (DL) exposure is now used to reduce pain and subjects are advised to protect the areas with sunscreen.
View Article and Find Full Text PDFThe neocortex undergoes extensive developmental growth, but how its architecture adapts to expansion remains largely unknown. Here, we investigated how early born Cajal-Retzius (CR) neurons, which regulate the assembly of cortical circuits, maintain a dense superficial distribution in the growing neocortex. We found that CR cell density is sustained by an activity-dependent importation of olfactory CR cells, which migrate into the neocortex after they have acted as axonal guidepost cells in the olfactory system.
View Article and Find Full Text PDFNumerous studies have shown that cerebellar function is related to the plasticity at the synapses between parallel fibers and Purkinje cells. How specific input patterns determine plasticity outcomes, as well as the biophysics underlying plasticity of these synapses, remain unclear. Here, we characterize the patterns of activity that lead to postsynaptically expressed LTP using both in vivo and in vitro experiments.
View Article and Find Full Text PDFKey Points: At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca(2+) entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid postsynaptic Ca(2+) signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics.
View Article and Find Full Text PDFBrimonidine at 0.18%, 1% and 2% concentrations applied topically in hairless mice significantly decreased tumor burden and incidences of erythema, flaking, wrinkling and skin thickening induced by UVR. The unbiased median week to tumor ≥1 mm was increased by the 1% and 2% concentrations.
View Article and Find Full Text PDFUnlabelled: The Sox family of transcription factors have been widely studied in the context of oligodendrocyte development. However, comparatively little is known about the role of Sox2, especially during CNS remyelination. Here we show that the expression of Sox2 occurs in oligodendrocyte progenitor cells (OPCs) in rodent models during myelination and in activated adult OPCs responding to demyelination, and is also detected in multiple sclerosis lesions.
View Article and Find Full Text PDFN-methyl-D-aspartate receptors (NMDARs) in cerebellar molecular layer interneurons (MLIs) are expressed and activated in unusual ways: at parallel fibre (PF) synapses they are only recruited by repetitive stimuli, suggesting an extrasynaptic location, whereas their activation by climbing fibre is purely mediated by spillover. NMDARs are thought to play an important role in plasticity at different levels of the cerebellar circuitry. Evaluation of the location, functional properties and physiological roles of NMDARs will be facilitated by knowledge of the NMDAR isoforms recruited.
View Article and Find Full Text PDFCaV3.1 T-type channels are abundant at the cerebellar synapse between parallel fibers and Purkinje cells where they contribute to synaptic depolarization. So far, no specific physiological function has been attributed to these channels neither as charge carriers nor more specifically as Ca(2+) carriers.
View Article and Find Full Text PDFPlasticity at the cerebellar parallel fiber to Purkinje cell synapse may underlie information processing and motor learning. In vivo, parallel fibers appear to fire in short high frequency bursts likely to activate sparsely distributed synapses over the Purkinje cell dendritic tree. Here, we report that short parallel fiber tetanic stimulation evokes a ∼7-15% depression which develops over 2 min and lasts for at least 20 min.
View Article and Find Full Text PDFTwenty-two of Galderma's proprietary compounds were tested in the GADD45α-GFP 'GreenScreen HC' assay (GS), the SOS-ChromoTest and the Mini-Ames to evaluate GSs performance for early genotoxicity screening purposes. Forty more characterized compounds were also tested, including antibiotics: metronidazole, clindamycin, tetracycline, lymecycline and neomycin; and catecholamines: resorcinol mequinol, hydroquinone, one aneugen carbendazim, one corticoid dexamethasone, one peroxisome proliferator-activated receptor rosiglitazone, one pesticide carbaryl and two further proprietary molecules with in vitro genotoxicity data. With proprietary molecules, this study concluded that the GS renders the SOS-ChromoTest obsolete for in vitro screening.
View Article and Find Full Text PDFPurpose: We designed this retrospective study to assess the frequency of difficult airway and difficult intubation in patients with spasmodic torticollis and compare it to that of the general population.
Methods: After Institutional Review Board approval, data were collected from the charts of all the patients with spasmodic torticollis who underwent selective peripheral denervation at our institution between 1988 and 2001. The intubation grade was determined using the Cormack and Lehane laryngoscopic classification.