DNMT3a in the hippocampal CA1 is crucial in the acquisition of morphine self‐administration in rats

Drug‐reinforced excessive operant responding is one fundamental feature of long-lasting addiction‐like behaviors and relapse in animals. However, the transcriptional regulatory mechanisms responsible for the persistent drug‐specific (not natural rewards) operant behavior are not entirely clear. In this study, we demonstrate a key role for one of the de novo DNA methyltransferase, DNMT3a, in the acquisition of morphine self‐administration (SA) in rats. The expression of DNMT3a in the hippocampal CA1 region but not in the nucleus accumbens shell was significantly up‐regulated after 1‐ and 7‐day morphine SA (0.3 mg/kg/infusion) but not after the yoked morphine injection. On the other hand, saccharin SA did not affect the expression of DNMT3a or DNMT3b. DNMT inhibitor 5‐aza‐2‐deoxycytidine (5‐aza) microinjected into the hippocampal CA1 significantly attenuated the acquisition of morphine SA. Knockdown of DNMT3a also impaired the ability to acquire the morphine SA. Overall, these findings suggest that DNMT3a in the hippocampus plays an important role in the acquisition of morphine SA and may be a valid target to prevent the development of morphine addiction. Includes Supplemental informatio

First sodium laser guide star asterism launching platform in China on 1.8m telescope at Gaomeigu Observatory

The application of sodium laser guide star is the key difference between modern adaptive optics system and traditional adaptive optics system. Especially in system like multi-conjugate adaptive optics, sodium laser guide star asterism which is formed by several laser guide stars in certain pattern is required to probe more atmospheric turbulence in different directions. To achieve this, a sodium laser guide star asterism launching platform is required. In this paper, we will introduce the sodium laser guide star asterism launching platform built and tested on the 1.8m telescope of the Gaomeigu Observatory. The platform has two functions: one is to compare the performance of sodium laser guide stars generated by different lasers at the same place; the other is to generate sodium laser guide star asterism with adjustable shape. The field test results at the beginning of 2021 verify the important role of the platform, which is also the first time to realize sodium laser guide star asterism in China

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

The aromatic/arginine selectivity filter of NIP aquaporins plays a critical role in substrate selectivity for silicon, boron, and arsenic

Nodulin-26-like intrinsic proteins (NIPs) of the aquaporin family are involved in the transport of diverse solutes, but the mechanisms controlling the selectivity of transport substrates are poorly understood. The purpose of this study was to investigate how the aromatic/arginine (ar/R) selectivity filter influences the substrate selectivity of two NIP aquaporins; the silicic acid (Si) transporter OsLsi1 (OsNIP2;1) from rice and the boric acid (B) transporter AtNIP5;1 from Arabidopsis; both proteins are also permeable to arsenite. Native and site-directed mutagenized variants of the two genes were expressed in Xenopus oocytes and the transport activities for Si, B, arsenite, and water were assayed. Substitution of the amino acid at the ar/R second helix (H2) position of OsLsi1 did not affect the transport activities for Si, B, and arsenite, but that at the H5 position resulted in a total loss of Si and B transport activities and a partial loss of arsenite transport activity. Conversely, changes of the AtNIP5;1 ar/R selectivity filter and the NPA motifs to the OsLsi1 type did not result in a gain of Si transport activity. B transport activity was partially lost in the H5 mutant but unaffected in the H2 mutant of AtNIP5;1. In contrast, both the single and double mutations at the H2 and/or H5 positions of AtNIP5;1 did not affect arsenite transport activity. The results reveal that the residue at the H5 position of the ar/R filter of both OsLsi1 and AtNIP5;1 plays a key role in the permeability to Si and B, but there is a relatively low selectivity for arsenite

Cinnamaldehyde up-regulates the mRNA expression level of TRPV1 receptor potential ion channel protein and its function in primary rat DRG neurons in vitro

Cinnamaldehyde (1) is a pharmacologically active ingredient isolated from cassia twig (Ramulus Cinnamomi), which is commonly used in herbal remedies to treat fever-related diseases. Both TRPV1 and TRPM8 ion channel proteins are abundantly expressed in sensory neurons, and are assumed to act as a thermosensor, with the former mediating the feeling of warmth and the latter the feeling of cold in the body. Both of them have recently been reported to be involved in thermoregulation. The purpose of this paper is to further uncover the antipyretic mechanisms of 1 by investigating its effects on the mRNA expression levels and functions of both TRPV1 and TRPM8. The results showed that 1 could up-regulate the mRNA expression levels of TRPV1 at both 37 and 39 degrees C, and its calcium-mediating function was significantly increased at 39 degrees C, all of which could not be blocked by pretreatment of the neuronal cells with ruthenium red, a general transient receptor potential (TRP) blocker, indicating that the action of 1 was achieved through a non-TRPA1 channel pathway. In conclusion, the findings in our in vitro studies might account for part of the peripheral molecular mechanisms for the antipyretic action of 1

Establishment and transfer of classical eyeblink conditioning using electrical microstimulation of the hippocampus as the conditioned stimulus.

The present experiment was designed to determine whether classical eyeblink conditioning (EBC) can be established by using electrical microstimulation of the hippocampus as a conditioned stimulus (CS) paired with an air-puff unconditioned stimulus (US). We intended to examine whether EBC transfer could occur when a CS was shifted between microstimulation of the hippocampus as a CS (Hip-CS) and tone as a CS (tone-CS) and to compare the difference in transfer effectiveness between delay EBC (dEBC) and trace EBC (tEBC). Eight groups of guinea pigs, including 4 experimental groups and 4 control groups, were included in the study. First, the experimental groups received either a Hip-CS or a tone-CS paired with a US; then, these groups were exposed to a shifted CS (tone-CS or Hip-CS) paired with the US. The control groups received the corresponding Hip-CS or tone-CS, which was, however, pseudo-paired with the US. The control groups were then shifted to the tone-CS (or Hip-CS) paired with the US. The results show that EBC can be successfully established when using microstimulation of the hippocampus as a CS paired with an air-puff US, and that the acquisition rates of EBC are higher in the experimental groups than in the control groups after switching from the Hip-CS to the tone-CS or vice versa, indicating the occurrence of learning transfer between EBC established with the Hip-CS and tone-CS. The present study also demonstrated that the EBC re-acquisition rates were remarkably higher in dEBC than in tEBC with both types of transfer, which suggests that the saving effect was more evident in dEBC than tEBC. These results significantly expand our knowledge of EBC transfer as well as the functional neural circuit underlying EBC transfer

Locations of the electrode tips in the hippocampus of guinea pigs.

<p>(A) A representative of toluidine blue-stained coronal hippocampus section (30 μm) from a guinea pig that received hippocampal electrical stimulation as the CS. Scale bar represents 1.0 mm; (B, C) Schematic illustration of the locations of all electrode tips. (B) For delay paradigm: (□ group of from Hip-CS (paired) to tone-CS (paired), n = 6; ■ group of from Hip-CS (pseudo-paired) to tone-CS (paired), n = 4; ○ group of from tone-CS (paired) to Hip-CS (paired), n = 7; ● group of from tone-CS (pseudo-paired) to Hip-CS (paired), n = 4); (C) For trace paradigm: (△ group of from Hip-CS (paired) to tone-CS (paired), n = 6; ▲ group of from Hip-CS (pseudo-paired) to tone-CS (paired), n = 4; ◇ group of from tone-CS (paired) to Hip-CS (paired), n = 5; ◆ group of from tone-CS (pseudo-paired) to Hip-CS (paired), n = 4). The coronal brain plates are adapted from the atlas of Rapisarda and Bacchelli [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178502#pone.0178502.ref039" target="_blank">39</a>].</p