M5 Muscarinic Receptors Mediate Striatal Dopamine Activation by Ventral Tegmental Morphine and Pedunculopontine Stimulation in Mice

Opiates, like other addictive drugs, elevate forebrain dopamine levels and are thought to do so mainly by inhibiting GABA neurons near the ventral tegmental area (VTA), in turn leading to a disinhibition of dopamine neurons. However, cholinergic inputs from the laterodorsal (LDT) and pedunculopontine (PPT) tegmental nucleus to the VTA and substantia nigra (SN) importantly contribute, as either LDT or PPT lesions strongly attenuate morphine-induced forebrain dopamine elevations. Pharmacological blockade of muscarinic acetylcholine receptors in the VTA or SN has similar effects. M5 muscarinic receptors are the only muscarinic receptor subtype associated with VTA and SN dopamine neurons. Here we tested the contribution of M5 muscarinic receptors to morphine-induced dopamine elevations by measuring nucleus accumbens dopamine efflux in response to intra-VTA morphine infusion using in vivo chronoamperometry. Intra-VTA morphine increased nucleus accumbens dopamine efflux in urethane-anesthetized wildtype mice starting at 10 min after infusion. These increases were absent in M5 knockout mice and were similarly blocked by pre-treatment with VTA scopolamine in wildtype mice. Furthermore, in wildtype mice electrical stimulation of the PPT evoked an initial, short-lasting increase in striatal dopamine efflux, followed 5 min later by a second prolonged increase in dopamine efflux. In M5 knockout mice, or following systemic pre-treatment with scopolamine in wildtype mice, the prolonged increase in striatal dopamine efflux was absent. The time course of increased accumbal dopamine efflux in wildtype mice following VTA morphine was consistent with both the prolonged M5-mediated excitation of striatal dopamine efflux following PPT electrical stimulation and accumbal dopamine efflux following LDT electrical stimulation. Therefore, M5 receptors appear critical for prolonged PPT excitation of dopamine efflux and for dopamine efflux induced by intra-VTA morphine

Forward Beam Monitor for the KATRIN experiment

The KArlsruhe TRItium Neutrino (KATRIN) experiment aims to measure the neutrino mass with a sensitivity of 0.2 eV (90 % CL). This will be achieved by a precision measurement of the endpoint region of the β-electron spectrum of tritium decay. The β-electrons are produced in the Windowless Gaseous Tritium Source (WGTS) and guided magnetically through the beamline. In order to accurately extract the neutrino mass the source activity is required to be stable and known to a high precision. The WGTS therefore undergoes constant extensive monitoring from several measurement systems. The Forward Beam Monitor (FBM) is one such monitoring system. The FBM system comprises a complex mechanical setup capable of inserting a detector board into the KATRIN beamline with a positioning precision of better than 0.3 mm. The electron flux density at that position is on the order of 10$^6$ s$^{-1}$ mm$^{-2}$. The detector board contains two silicon detector chips of p-i-n diode type which can measure the β-electron flux from the source with a precision of 0.1 % within 60 s with an energy resolution of FWHM = 2 keV. The unique challenge in developing the FBM arises from its designated operating environment inside the Cryogenic Pumping Section which is a potentially tritium contaminated ultra-high vacuum chamber at cryogenic temperatures in the presence of a 1 T strong magnetic field. Each of these parameters do strongly limit the choice of possible materials which e.g. caused difficulties in detector noise reduction, heat dissipation and lubrication. In order to completely remove the FBM from the beam tube a 2 m long traveling distance into the beamline is needed demanding a robust as well as highly precise moving mechanism

A Bisognano-Wichmann-like Theorem in a Certain Case of a Non Bifurcate Event Horizon related to an Extreme Reissner-Nordstr\"om Black Hole

Thermal Wightman functions of a massless scalar field are studied within the framework of a ``near horizon'' static background model of an extremal R-N black hole. This model is built up by using global Carter-like coordinates over an infinite set of Bertotti-Robinson submanifolds glued together. The analytical extendibility beyond the horizon is imposed as constraints on (thermal) Wightman's functions defined on a Bertotti-Robinson sub manifold. It turns out that only the Bertotti-Robinson vacuum state, i.e. $T=0$, satisfies the above requirement. Furthermore the extension of this state onto the whole manifold is proved to coincide exactly with the vacuum state in the global Carter-like coordinates. Hence a theorem similar to Bisognano-Wichmann theorem for the Minkowski space-time in terms of Wightman functions holds with vanishing ``Unruh-Rindler temperature''. Furtermore, the Carter-like vacuum restricted to a Bertotti-Robinson region, resulting a pure state there, has vanishing entropy despite of the presence of event horizons. Some comments on the real extreme R-N black hole are given

The KATRIN Pre-Spectrometer at reduced Filter Energy

The KArlsruhe TRItium Neutrino experiment, KATRIN, will determine the mass of the electron neutrino with a sensitivity of 0.2 eV (90% C.L.) via a measurement of the beta-spectrum of gaseous tritium near its endpoint of E_0 =18.57 keV. An ultra-low background of about b = 10 mHz is among the requirements to reach this sensitivity. In the KATRIN main beam-line two spectrometers of MAC-E filter type are used in a tandem configuration. This setup, however, produces a Penning trap which could lead to increased background. We have performed test measurements showing that the filter energy of the pre-spectrometer can be reduced by several keV in order to diminish this trap. These measurements were analyzed with the help of a complex computer simulation, modeling multiple electron reflections both from the detector and the photoelectric electron source used in our test setup.Comment: 22 pages, 12 figure