Nemlineáris optika és spektroszkópia a THz (távoli infravörös) tartományon = Nonlinear optics and spectroscopy on the THz (far-infrared) range

Felépítettük az első magyarországi THz-es laboratóriumot. Ez egy nem OTKA forrásból vásárolt, 1 mJ energiájú impulzusok 1 kHz-el történő előállítására alkalmas diódapumpált szilárdtest lézeren alapul. Ezeknek az impulzusoknak az optikai egyenirányításával nagyobb, mint 0.5 mikroJ energiájú egyciklusú THz-es impulzusokat állítunk elő. Ezekkel nemcsak lineáris időbeli terahertzes spektroszkópiai (TDTS) méréseket, hanem nemlineáris TDTS méréseket is tudunk végezni. Modellszámításokkal megmutattuk, hogy a korábban használtnál hosszabb pumpáló lézerimpulzusokkal (jelentősen nagyobb hatásfokkal) jelentősen nagyobb THz-es impulzusenergiák érhetők el. Ezt az elméleti eredményt kísérletileg bizonyítottuk, 125 mikroJ (világrekord) energiájú THz-es impulzusokat állítottunk elő. A modellszámítások szerint a kristály hűtése további jelentős energianövekedést fog eredményezni. Megterveztünk egy kontaktrácsos elrendezést, amellyel több mJ energiájú THz-es impulzusokat lehet majd előállítani. Ezek fókuszálásával várhatóan 100 MV/cm térerősséget is el lehet majd érni. Modellszámításokkal megmutattuk, hogy több 10 MV/cm maximális térerősségű THz-es impulzusokkal többszázszorosan meg lehet növelni a magas-harmonikus keltés hatásfokát a levágási frekvencia közelében, el lehet érni, hogy csak egy attoszekundumos impulzus keletkezzen pumpáló ciklusonként, 100 fs hosszú 10 fC töltésű relativisztikus elektroncsomagot össze lehet nyomni 100 as-ra. | The first Hungarian THz laboratory has been built up. It is based on a DPSS pump laser with 1 mJ pulse energy and 1 kHz repetition rate (purchased from non-OTKA funding). By OR of these pump pulses, single-cycle THz pulses with larger than 0.5 ?J energy have been generated. These THz pulses can also be used to nonlinear time-domain THz spectroscopy (TDTS) measurements, besides linear TDTS measurements. We have shown by model calculations that by using pump pulses with pulse duration longer than used previously, the THz pulse energy can be significantly increased with a simultaneous increase of the THz generation efficiency. This theoretical prediction has been experimentally verified. We have generated THz pulses with the highest so far 125 ?J energy. Our calculations predict additional substantial increase in the THz energy by cooling the nonlinear crystal. A contact grating setup has been designed, which will enable the generation of THz pulses with multi-mJ energy. 100 MV/cm peak electric field is expected by focusing these THz pulses. We have shown by model calculations that the efficiency of high-order harmonic generation in the cut-off region can be increased several 100 times by using THz pulses with multi-10-MV/cm peak electric field. Also, in such a THz-assisted scheme, single attosecond pulses can be generated in each optical cycle of the driving field. 100 fs long relativistic electron bunches with 10 fC charge can be compressed to 100 as

Resolvin D1 and D2 inhibit transient receptor potential vanilloid 1 and ankyrin 1 ion channel activation on sensory neurons via lipid raft modification

Transient Receptor Potential Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons and regulate nociceptor and inflammatory functions. Resolvins are endogenous lipid mediators. Resolvin D1 (RvD1) is described as a selective inhibitor of TRPA1-related postoperative and inflammatory pain in mice acting on the G protein-coupled receptor DRV1/GPR32. Resolvin D2 (RvD2) is a very potent TRPV1 and TRPA1 inhibitor in DRG neurons, and decreases inflammatory pain in mice acting on the GPR18 receptor, via TRPV1/TRPA1-independent mechanisms. We provided evidence that resolvins inhibited neuropeptide release from the stimulated sensory nerve terminals by TRPV1 and TRPA1 activators capsaicin (CAPS) and allyl-isothiocyanate (AITC), respectively. We showed that RvD1 and RvD2 in nanomolar concentrations significantly decreased TRPV1 and TRPA1 activation on sensory neurons by fluorescent calcium imaging and inhibited the CAPS-and AITC-evoked45Ca-uptake on TRPV1-and TRPA1-expressing CHO cells. Since CHO cells are unlikely to express resolvin receptors, resolvins are suggested to inhibit channel opening through surrounding lipid raft disruption. Here, we proved the ability of resolvins to alter the membrane polarity related to cholesterol composition by fluorescence spectroscopy. It is concluded that targeting lipid raft integrity can open novel peripheral analgesic opportunities by decreasing the activation of nociceptors. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Single-Molecule Imaging Reveals Rapid Estradiol Action on the Surface Movement of AMPA Receptors in Live Neurons

Gonadal steroid 17β-estradiol (E2) exerts rapid, non-genomic effects on neurons and strictly regulates learning and memory through altering glutamatergic neurotransmission and synaptic plasticity. However, its non-genomic effects on AMPARs are not well understood. Here, we analyzed the rapid effect of E2 on AMPARs using single-molecule tracking and super-resolution imaging techniques. We found that E2 rapidly decreased the surface movement of AMPAR via membrane G protein-coupled estrogen receptor 1 (GPER1) in neurites in a dose-dependent manner. The cortical actin network played a pivotal role in the GPER1 mediated effects of E2 on the surface mobility of AMPAR. E2 also decreased the surface movement of AMPAR both in synaptic and extrasynaptic regions on neurites and increased the synaptic dwell time of AMPARs. Our results provide evidence for understanding E2 action on neuronal plasticity and glutamatergic neurotransmission at the molecular level

Carboxamido steroids inhibit the opening properties of Transient Receptor Potential ion channels by lipid raft modulation

Transient Receptor Potential (TRP) cation channels, like the TRP Vanilloid 1 and TRP Ankyrin 1 (TRPV1 and TRPA1) are expressed on primary sensory neurons. These thermosensor channels play role in pain processing. We provided evidence that lipid raft disruption influenced the TRP channel activation and a carboxamido-steroid compound (C1) inhibited TRPV1 activation. Therefore, our aim was to investigate whether this compound exerts its effect through lipid raft disruption and the steroid backbone (C3) or altered position of the carboxamido group (C2) influence the inhibitory action by measuring Ca2+-transients on isolated neurons and calcium-uptake on receptor-expressing CHO cells. Membrane cholesterol content was measured by filipin staining and membrane polarisation by fluorescence spectroscopy. Both the percentage of responsive cells and the magnitude of the intracellular Ca2+-enhancement evoked by the TRPV1 agonist capsaicin were significantly inhibited after C1 and C2 incubation, but not after C3 administration. C1 was able to reduce other TRP channel activation as well. The compounds induced cholesterol depletion in CHO cells, but only C1 induced changes in membrane polarisation. The inhibitory action of the compounds on TRP channel activation develops by lipid raft disruption, and the presence and the position of the carboxamido group is essential