Faculty Bibliography

Aplydactone is an unusual brominated sesquiterpenoid isolated from the sea hare Aplysia dactylomela. Its highly strained skeleton contains two four- and three six-membered rings and features three adjacent quaternary carbon atoms. Although it is most likely of photochemical origin, attempts to generate it from a chamigrane precursor have failed thus far. In this work, we present a total synthesis of aplydactone that relies on two photochemical key steps that are not biomimetic but highly effective in establishing the two cyclobutane rings. Our synthesis also features an unusual Barbier-type cyclization and culminates in new radical conditions to install the sterically hindered secondary bromide of the natural product.

Azobenzenes are versatile photoswitches that can be cycled between their trans- and cis-configuration with light. The wavelengths required for this isomerization are substantially shifted from the UV to the visible range through tetra-ortho-chlorination. These halogenated azobenzenes display unique photoswitching characteristics, but their syntheses remain limited and inefficient. A new general method for the synthesis of tetra-ortho-chloro azobenzenes has been developed, which relies on direct palladium(II)-catalyzed C-H activation of pre-existing standard azobenzenes. This late-stage functionalization has a broad substrate scope and can be used to create a variety of useful building blocks for the construction of more elaborate redshifted photopharmaceuticals. This method is used to prepare red-AzCA-4, a photoswitchable vanilloid that enables optical control of the cation channel TRPV1 with visible light.

G-protein coupled inwardly rectifying potassium channels (GIRKs) are ubiquitously expressed throughout the human body and are an integral part of inhibitory signal transduction pathways. Upon binding of Gbetagamma subunits released from G-protein coupled receptors (GPCRs), GIRK channels open and reduce the activity of excitable cells via hyperpolarization. As such, they play a role in cardiac output, the coordination of movement and cognition. Due to their involvement in a multitude of pathways, the precision control of GIRK channels is an important endeavour. Here, we describe the development of the photoswitchable agonist LOGO (the Light Operated GIRK-channel Opener), which activates GIRK channels in the dark and is rapidly deactivated upon exposure to long wavelength UV irradiation. LOGO is the first K+ channel opener and selectively targets channels that contain the GIRK1 subunit. It can be used to optically silence action potential firing in dissociated hippocampal neurons and LOGO exhibits activity in vivo, controlling the motility of zebrafish larvae in a light dependent fashion. We envisage that LOGO will be a valuable research tool to dissect the function of GIRK channels from other GPCR dependent signalling pathways.

PURPOSE: To design, construct and validate radiofrequency (RF) transmit and receive phased array coils for high-resolution visual cortex imaging at 7 Tesla. METHODS: A 4 channel transmit and 16 channel receive array was constructed on a conformal polycarbonate former. Transmit field efficiency and homogeneity were simulated and validated, along with the Specific Absorption Rate, using [Formula: see text] mapping techniques and electromagnetic simulations. Receiver signal-to-noise ratio (SNR), temporal SNR (tSNR) across EPI time series, g-factors for accelerated imaging and noise correlations were evaluated and compared with a commercial 32 channel whole head coil. The performance of the coil was further evaluated with human subjects through functional MRI (fMRI) studies at standard and submillimeter resolutions of upto 0.8mm isotropic. RESULTS: The transmit and receive sections were characterized using bench tests and showed good interelement decoupling, preamplifier decoupling and sample loading. SNR for the 16 channel coil was approximately 1.5 times that of the commercial coil in the human occipital lobe, and showed better g-factor values for accelerated imaging. fMRI tests conducted showed better response to Blood Oxygen Level Dependent (BOLD) activation, at resolutions of 1.2mm and 0.8mm isotropic. CONCLUSION: The 4 channel phased array transmit coil provides homogeneous excitation across the visual cortex, which, in combination with the dual row 16 channel receive array, makes for a valuable research tool for high resolution anatomical and functional imaging of the visual cortex at 7T.

There is a long-standing debate about the neurocognitive implementation of mental imagery. One form of mental imagery is the imagery of visual motion, which is of interest due to its naturalistic and dynamic character. However, so far only the mere occurrence rather than the specific content of motion imagery was shown to be detectable. In the current study, the application of multi-voxel pattern analysis to high-resolution functional data of 12 subjects acquired with ultra-high field 7T functional magnetic resonance imaging allowed us to show that imagery of visual motion can indeed activate the earliest levels of the visual hierarchy, but the extent thereof varies highly between subjects. Our approach enabled classification not only of complex imagery, but also of its actual contents, in that the direction of imagined motion out of four options was successfully identified in two thirds of the subjects and with accuracies of up to 91.3% in individual subjects. A searchlight analysis confirmed the local origin of decodable information in striate and extra-striate cortex. These high-accuracy findings not only shed new light on a central question in vision science on the constituents of mental imagery, but also show for the first time that the specific sub-categorical content of visual motion imagery is reliably decodable from brain imaging data on a single-subject level.

Interindividual differences play a crucial role in research on mental imagery. The inherently private nature of imagery does not allow for the same experimental control that is possible in perception research. Even when there are precise instructions subjects will differ in their particular imagery strategy and, hence, show different brain activations. Here, we show results of a time-resolved searchlight analysis for 12 individual subjects who perform a visual motion imagery task. The data show the spatial and temporal extent of brain areas and time windows that allow for a successful decoding of the direction of imagined motion out of four options. Accuracy maps for six different time windows are shown for every individual subject and are made freely available on NeuroVault. These data accompany the findings in the publication "Decoding the direction of imagined visual motion using 7 T ultra-high field fMRI" (Emmerling et al., 2016) [1].

Release of neuroactive substances by exocytosis from dendrites is surprisingly widespread and is not confined to a particular class of transmitters: it occurs in multiple brain regions, and includes a range of neuropeptides, classical neurotransmitters, and signaling molecules, such as nitric oxide, carbon monoxide, ATP, and arachidonic acid. This review is focused on hypothalamic neuroendocrine cells that release vasopressin and oxytocin and midbrain neurons that release dopamine. For these two model systems, the stimuli, mechanisms, and physiological functions of dendritic release have been explored in greater detail than is yet available for other neurons and neuroactive substances. (c) 2017 American Physiological Society. Compr Physiol 7:235-252, 2017.