Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Spt6 is a maintenance factor for centromeric CENP-A

Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centromere-specific histone dCENP-A in M/G1 phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and dCENP-A mutants carrying phosphomimetic residues alleviate this association. Retention of phosphomimetic dCENP-A mutants is reduced relative to wildtype, while non-phosphorylatable dCENP-A retention is increased and accumulates at the centromere. We conclude that Spt6 acts as a conserved CENP-A maintenance factor that ensures long-term stability of epigenetic centromere identity during transcription-mediated chromatin remodeling

Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis

Rationale: An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia. Objectives: The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG. Methods: A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21–45 Hz) was investigated (n=13 pairs+4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n=15). Results: In the resting state, there was a significant condition × frequency interaction (p=0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21–27 Hz] and increased low gamma [27–45 Hz]). There was also a condition × frequency × location interaction (p=0.006), such that the reduction in 21–27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27–45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r=0.429, p=0.042). In the motor task, there was a main effect of THC to increase 65–130-Hz ERS (p=0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85–130-Hz band (p=0.02) and not the 65–85-Hz band. Conclusions: The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state

Collection of the thinnest: A unique eggshell assemblage from the Late Cretaceous vertebrate locality of Iharkút (Hungary)

As a result of several years of screen-washing activity, a remarkable assemblage of eggshell fragments has been recovered from the Late Cretaceous vertebrate locality of Iharkút, Hungary. Detailed investigation of the assemblage by multiple visualization techniques (scanning electron microscopy, polarizing light microscopy, X-ray micro-computed tomography), quantitative morphometric analyses, and micro X-ray fluorescence spectrometry revealed a diverse composition of five different eggshell morphotypes (MT I-MT V) and three subcategories within the second morphotype (MT II/a, b, c), with MT I being by far the most abundant (83%) in the assemblage. MT I, MT III, and MT V represent theropod dinosaurian eggshells, whereas MT II and MT IV show characteristics of crocodilian and squamate eggshells, respectively. Hence, despite their fragmentary nature, these eggshells represent the first clear evidence that various sauropsid taxa had nesting sites near the ancient fluvial system of Iharkút. Besides the implied taxonomic diversity, two unique features add to the significance of this eggshell assemblage. First, it contains the thinnest rigid crocodilian (MT II/c) and squamate (MT IV) eggshells ever reported. Moreover, one of the identified theropod morphotypes, MT I, is also among the thinnest fossil dinosaurian eggshells, the thinness of which is only rivalled by the eggshells of the smallest Mesozoic avian eggs known to date. Second, the Iharkút eggshell assemblage consists exclusively of thin eggshells (≤300 μm), a condition unknown from any other fossil eggshell assemblages described to date. Combined with the knowledge acquired from skeletal remains, these peculiarities give additional insights into the paleoecology of the terrestrial sauropsid fauna once inhabiting the ancient island of Iharkút. Finally, the presence of well-preserved eggshells recovered from two different sites representing different depositional environments provides further evidence for previous taphonomic and sedimentological conclusions, and also expands our knowledge of the special conditions that allowed the preservation of these delicate eggshell fragments. © 2017 The Author(s)