In vivo whole-cell recording from morphologically identified mouse superior colliculus neurons

In vivo whole-cell recording when combined with morphological characterization after biocytin labeling is a powerful technique to study subthreshold synaptic processing in cell-type-identified neuronal populations. Here, we provide a step-by-step procedure for performing whole-cell recordings in the superior colliculus of urethane-anesthetized mice, a major visual processing region in the rodent brain. Two types of visual stimulation methods are described. While we focus on superior colliculus neurons, this protocol is applicable to other brain areas.Comment: 29 pages including 4 figure

Timing in the cerebellum during motor learning: from neuron to athlete to patient

The cerebellum is involved in the encoding and integration of spatial and temporal information. Although these processes are crucial to our survival, the neuronal mechanisms the cerebellum utilizes to carry out this type of spatio-temporal processing, as well as the precise cerebellar contribution to temporal aspects of various behaviors, remain to be clarified. The research in this doctoral thesis describes findings from experiments done in rodents and humans, with a particular focus on cerebellar timing mechanisms. In rodents, neuronal circuit mechanisms underlying eyeblink conditioning are investigated. The contribution of pontocerebellar mossy fibers and perineuronal nets in the cerebellar nuclei to associative learning are examined. In humans, cerebellar involvement in action observation and spatio-temporal trajectory prediction are investigated in spinocerebellar ataxia type 6 (SCA6) patients, healthy controls and baseball athletes. Together, these studies demonstrate that the cerebellum is important for temporal processes during a range of behaviors, while revealing the neuronal circuit responsible

High proton conductivity in cyanide-bridged metal-organic frameworks: understanding the role of water

We investigate and discuss the proton conductivity properties of the cyanide-bridged metal–organic framework (MOF) [Nd(mpca)2Nd(H2O)6Mo(CN)8]·nH2O (where mpca is 5-methyl-2-pyrazinecarboxylate). This MOF is one of an exciting class of cyanide-bridged materials that can combine porosity with magnetism, luminescence, and proton conductivity. Specifically, we show that this material features highly hydrophilic open channels filled with water molecules. They enable a high proton conductivity, as much as 10−3 S cm−1. A rich hydrogen-bonding network, formed by the ligands' carboxylate groups with both coordinated and lattice water molecules, facilitates this high proton conductivity. Combined thermogravimetric studies, FTIR spectroscopy and PXRD analysis show that upon heating at 80 °C, the lattice water molecules are removed without any change in the framework. Further heating at 130 °C results in a partial removal of the coordinated water molecules, while still retaining the original framework. These activated MOFs shows an increasing conductivity from ∼10−9 S cm−1 to ∼10−3 S cm−1 when the relative humidity increases from 0% to 98%. Our studies show that the increase in proton conductivity is correlated with the re-hydration of the framework with lattice water molecules. The Arrhenius activation energy for the proton conductivity process is low (Ea = 37 kJ mol−1), indicating that the protons “hop” through the channels following the Grotthuss mechanism. The fact that this MOF is remarkably stable both under high humidity conditions and at relatively high temperatures (up to 130 °C) makes it a good candidate for real-life applications

Synaptic mechanisms for associative learning in the cerebellar nuclei

Associative learning during delay eyeblink conditioning (EBC) depends on an intact cerebellum. However, the relative contribution of changes in the cerebellar nuclei to learning remains a subject of ongoing debate. In particular, little is known about the changes in synaptic inputs to cerebellar nuclei neurons that take place during EBC and how they shape the membrane potential of these neurons. Here, we probed the ability of these inputs to support associative learning in mice, and investigated structural and cell-physiological changes within the cerebellar nuclei during learning. We find that optogenetic stimulation of mossy fiber afferents to the anterior interposed nucleus (AIP) can substitute for a conditioned stimulus and is sufficient to elicit conditioned responses (CRs) that are adaptively well-timed. Further, EBC induces structural changes in mossy fiber and inhibitory inputs, but not in climbing fiber inputs, and it leads to changes in subthreshold processing of AIP neurons that correlate with conditioned eyelid movements. The changes in synaptic and spiking activity that precede the CRs allow for a decoder to distinguish trials with a CR. Our data reveal how structural and physiological modifications of synaptic inputs to cerebellar nuclei neurons can facilitate learning.</p

Synaptic mechanisms for associative learning in the cerebellar nuclei

Associative learning during delay eyeblink conditioning (EBC) depends on an intact cerebellum. However, the relative contribution of changes in the cerebellar nuclei to learning remains a subject of ongoing debate. In particular, little is known about the changes in synaptic inputs to cerebellar nuclei neurons that take place during EBC and how they shape the membrane potential of these neurons. Here, we probed the ability of these inputs to support associative learning in mice, and investigated structural and cell-physiological changes within the cerebellar nuclei during learning. We find that optogenetic stimulation of mossy fiber afferents to the anterior interposed nucleus (AIP) can substitute for a conditioned stimulus and is sufficient to elicit conditioned responses (CRs) that are adaptively well-timed. Further, EBC induces structural changes in mossy fiber and inhibitory inputs, but not in climbing fiber inputs, and it leads to changes in subthreshold processing of AIP neurons that correlate with conditioned eyelid movements. The changes in synaptic and spiking activity that precede the CRs allow for a decoder to distinguish trials with a CR. Our data reveal how structural and physiological modifications of synaptic inputs to cerebellar nuclei neurons can facilitate learning.</p

Design of the NL-ENIGMA study: Exploring the effect of Souvenaid on cerebral glucose metabolism in early Alzheimer's disease

Alzheimer's disease is associated with early synaptic loss. Specific nutrients are known to be rate limiting for synapse formation. Studies have shown that administering specific nutrients may improve memory function, possibly by increasing synapse formation. This Dutch study explores the Effect of a specific Nutritional Intervention on cerebral Glucose Metabolism in early Alzheimer's disease (NL-ENIGMA, Dutch Trial Register NTR4718, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4718). The NL-ENIGMA study is designed to test whether the specific multinutrient combination Fortasyn Connect present in the medical food Souvenaid influences cerebral glucose metabolism as a marker for improved synapse function. Methods This study is a double-blind, randomized controlled parallel-group single-center trial. Forty drug-naive patients with mild cognitive impairment or mild dementia with evidence of amyloid deposition are 1:1 randomized to receive either the multinutrient combination or placebo once daily. Main exploratory outcome parameters include absolute quantitative positron emission tomography with 18F-fluorodeoxyglucose (including arterial sampling) and standard uptake value ratios normalized for the cerebellum or pons after 24 weeks. Discussion We expect the NL-ENIGMA study to provide further insight in the potential of this multinutrient combination to improve synapse function

A stabilised finite element method for the convection-diffusion-reaction equation in mixed form

This paper is devoted to the approximation of the convection-diffusion-reaction equation using a mixed, first-order, formulation. We propose, and analyse, a stabilised finite element method that allows equal order interpolations for the primal and dual variables. This formulation, reminiscent of the Galerkin least-squares method, is proven stable and convergent. In addition, a numerical assessment of the numerical performance of different stabilised finite element methods for the mixed formulation is carried out, and the different methods are compared in terms of accuracy, stability, and sharpness of the layers for two different classical test problems