An MR-compatible antenna and application in a murine superficial hyperthermia applicator

In this work, a novel magnetic resonance (MR)-compatible microwave antenna was designed and validated in a small animal superficial hyperthermia applicator. The antenna operates at 2.45 GHz and matching is made robust against production and setup inaccuracies. To validate our theoretical concept, a prototype of the applicator was manufactured and tested for its properties concerning input reflection, sensitivity for setup inaccuracies, environment temperature stability and MR-compatibility. The experiments show that the applicator indeed fulfils the requirements for MR-guided hyperthermia investigation in small animals: it creates a small heating focus (<1 cm3), has a stable and reliable performance (S11< −15 dB) for all working conditions and is MR-compatible

Corticothalamic Spike Transfer via the L5B-POm Pathway in vivo

The cortex connects to the thalamus via extensive corticothalamic (CT) pathways, but their function in vivo is not well understood. We investigated "top-down" signaling from cortex to thalamus via the cortical layer 5B (L5B) to posterior medial nucleus (POm) pathway in the whisker system of the anesthetized mouse. While L5B CT inputs to POm are extremely strong in vitro, ongoing activity of L5 neurons in vivo might tonically depress these inputs and thereby block CT spike transfer. We find robust transfer of spikes from the cortex to the thalamus, mediated by few L5B-POm synapses. However, the gain of this pathway is not constant but instead is controlled by global cortical Up and Down states. We characterized in vivo CT spike transfer by analyzing unitary PSPs and found that a minority of PSPs drove POm spikes when CT gain peaked at the beginning of Up states. CT gain declined sharply during Up states due to frequency-dependent adaptation, resulting in periodic high gain-low gain oscillations. We estimate that POm neurons receive few (2-3) active L5B inputs. Thus, the L5B-POm pathway strongly amplifies the output of a few L5B neurons and locks thalamic POm sub-and suprathreshold activity to cortical L5B spiking

Cortical Dependence of Whisker Responses in Posterior Medial Thalamus In Vivo

Cortical layer 5B (L5B) thick-tufted pyramidal neurons have reliable responses to whisker stimulation in anesthetized rodents. These cells drive a corticothalamic pathway that evokes spikes in thalamic posterior medial nucleus (POm). While a subset of POm has been shown to integrate both cortical L5B and paralemniscal signals, the majority of POm neurons are suggested to receive driving input from L5B only. Here, we test this possibility by investigating the origin of whisker-evoked responses in POm and specifically the contribution of the L5B-POm pathway. We compare L5B spiking with POm spiking and subthreshold responses to whisker deflections in urethane anesthetized mice. We find that a subset of recorded POm neurons shows early (< 50 ms) spike responses and early large EPSPs. In these neurons, the early large EPSPs matched L5B input criteria, were blocked by cortical inhibition, and also interacted with spontaneous Up state coupled large EPSPs. This result supports the view of POm subdivisions, one of which receives whisker signals predominantly via L5B neurons

Optical control of L-Type Ca2+ channels using a diltiazem photoswitch

L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control

Organization and somatotopy of corticothalamic projections from L5B in mouse barrel cortex

Neurons in cortical layer 5B (L5B) connect the cortex to numerous subcortical areas. Possibly the best-studied L5B cortico-subcortical connection is that between L5B neurons in the rodent barrel cortex (BC) and the posterior medial nucleus of the thalamus (POm). However, the spatial organization of L5B giant boutons in the POm and other subcortical targets is not known, and therefore it is unclear if this descending pathway retains somatotopy, i. e., body map organization, a hallmark of the ascending somatosensory pathway. We investigated the organization of the descending L5B pathway from the BC by dual-color anterograde labeling. We reconstructed and quantified the bouton clouds originating from adjacent L5B columns in the BC in three dimensions. L5B cells target six nuclei in the anterior midbrain and thalamus, including the posterior thalamus, the zona incerta, and the anterior pretectum. The L5B subcortical innervation is target specific in terms of bouton numbers, density, and projection volume. Common to all target nuclei investigated here is the maintenance of projection topology from different barrel columns in the BC, albeit with target-specific precision. We estimated low cortico-subcortical convergence and divergence, demonstrating that the L5B corticothalamic pathway is sparse and highly parallelized. Finally, the spatial organization of boutons and whisker map organization revealed the subdivision of the posterior group of the thalamus into four subnuclei (anterior, lateral, medial, and posterior). In conclusion, corticofugal L5B neurons establish a widespread cortico-subcortical network via sparse and somatotopically organized parallel pathways

Research Data for: Panoramic visual statistics shape retina-wide organization of receptive fields

Statistics of natural scenes are not uniform - their structure varies dramatically from ground to sky. It remains unknown whether these non-uniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. We show experimentally that, in agreement with our predictions, receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell-types

Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling

To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo

Spatially selective nucleation of metal clusters on the tobacco mosaic virus

Tobacco mosaic virus (TMV) is a very stable nanotube complex of a helical RNA and 2130 coat proteins. The special shape makes it an interesting nano-object, especially as a template for chemical reactions. Here we use TMV as a chemically functionalized template for binding metal ions. Different chemical groups of the coat protein can be used as ligands or to electrostatically bind metal ions. Following this activation step, chemical reduction and electroless plating produces metal clusters of several nanometers in diameter. The clusters are attached to the virion without destroying its structure. Gold clusters generated from an ascorbic acid bath bind to the exterior surface as well as to the central channel of the hollow tube. Very high selectivity is reached by tuning Pd-II and Pt-II activations with phosphate: When TMV is first activated with Pd-II, and thereafter metallized with a nickel-phosphinate bath, 3 nm nickel clusters grow in the central channel; when TMV from phosphate-buffered suspensions is employed, larger nickel clusters grow on the exterior surface. Phosphate buffers have to be avoided when 3 nm nickel and cobalt wires of several 100 nm in length are synthesized from borane-based baths inside the TMV channel. The results are discussed with respect to the inorganic complex chemistry of precursor molecules and the distribution of binding sites in TMV