Banca de DEFESA: ANNIE DA COSTA SOUZA
Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANNIE DA COSTA SOUZA
DATE: 29/04/2020
TIME: 09:00
LOCAL: SERÁ REALIZADA POR VÍDEO CONFERÊNCIA
TITLE:
PSYCHEDELIC STATES AND SLEEP IN THE RAT BRAIN: BEHAVIORAL, ELECTROPHYSIOLOGICAL AND MOLECULAR STUDIES
KEY WORDS:
psychedelics, serotonin, hippocampus, prefrontal cortex, somatosensory cortex, rat, electrophysiology, sleep, phosphoproteomics
PAGES: 285
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:
Classic psychedelics (or hallucinogens) are substances known for altering consciousness. Early experiments on several classic psychedelics demonstrated that their psychoactive effect is dependent on 5-HT2A and 5-HT1A serotonergic receptors, but due to the long prohibition of these drugs, little is known about their electrophysiological effects on the brain. In the current work I set out to investigate the effects of 5-MeO-DMT and d-LSD, two potent serotonergic agonists, on the local field potentials (LFP) recorded from the hippocampus and prefrontal cortex of rats. Typical behavioral alterations ~15 min after drug injection were observed, such as increased locomotion, increased space occupancy, and the occurrence of stereotyped behaviors (wet-dog shake, uncoordinated gaiting etc). Similar to previous results, LFP alterations were detected in prefrontal cortical areas (PFC), as well as in the hippocampus (HP). The power in the Theta (5-12 Hz) and Gamma band (30-100 Hz) decreased in the two areas within the first 30 min after (i.p. and i.c.v.) 5-MeO-DMT injection for all experiments, except for the highest dose of 5-MeO-DMT (i.c.v.) in the PFC. Likewise, we found a similar result for d-LSD in the long-term analysis, there was a decrease in the Gamma power after ~4h30min after d-LSD (i.p.) injection. We found that power in the delta (0.5-4 Hz) band did not change significantly.
Moreover, coherence analysis revealed that 5-MeO-DMT (i.p.) increased the coherence between HP and PFC in the Delta and Theta range. Next, I assessed how similar the changes caused by classic psychedelics are to the changes observed across the sleep-wake cycle. State map analysis revealed that both substances promoted a shift in the spectral profile typical of waking (WK) towards that of slow-wave sleep (SWS) or intermediated sleep (IS)/REM. Although animals remain awake after being treated with psychedelics, it is not a normal WK in terms of the LFP spectral profile. While some of the results obtained corroborate previous studies (e.g., the decrease in gamma power in the PFC), I also found divergent results, such as the decrease in PFC theta power. Altogether, the results are novel and promote a better understanding of the neurophysiological alterations caused by classic hallucinogens.
The second chapter of this thesis is dedicated to the investigation of the cognitive role of the distinct sleep stages in terms of the molecular (and electrophysiological) correlates. We hypothesized that the SWS and REM sleep play distinct roles in memory processing during sleep and that the phosphoproteomic profiles are as well distinct. More specifically, we screened the phosphorylated proteins of the somatosensory cortex and the hippocampus of during both sleep stages of animals that were exposed or not exposed to novelty in the previous waking.
It is known that besides its restorative role, sleep plays an important role in memory consolidation and cognition. However little is known on the molecular mechanism that underlies this function, and which dynamic it would have across the different sleep stages (SWS and REM sleep). In a previous work of our group, we have demonstrated that phosphorylated CaMKIIalpha, a kinase protein related to synaptic plasticity, is down-regulated during SWS and up-regulated during REM sleep in the hippocampus of rats exposed to novelty in the previous waking. This work has motivated follow-up research with the question: which are the other proteins that modulated in a sleep stage-dependent manner? In order to answer this question, we made similar experiments using a proteomic approach looking for protein phosphorylation markers. We identified a total of 2334 proteins in both brain regions of HP and primary somatosensory cortex (S1). Among the identified proteins we found a variety that was significantly modulated across the sleep cycle. The ontogenetic analysis revealed that the modulated proteins belong to several classes, for instance, cytoskeleton organization, RNA processing, calcium signalling pathways etc. In terms of quantitative analysis, the animals from slow-wave sleep group that were previously exposed to novelty presented 9 modulated proteins in the hippocampus, while 23 in the S1 region compared to non-exposed animals. In the same way, REM sleep exposed animals had 3 modulated proteins in the HP and 3 in the S1 compared to the non-exposed animals. Overall the results point that novelty-induced changes in protein phosphorylation levels are more pronounced in the S1 cortex than in HP, and that this seems to occur mainly during SWS. Possibly, this upward, as well as the downward modulation, could be related to the characteristics of the up and down state of the slow oscillations of SWS. On the other hand, during REM sleep, there are fewer modulated proteins. A variety of functions were identified and a great part of that refers to the general functioning of the neurons, especially during SWS. However, once that novelty is present, such stimuli would narrow the phosphorylation to a more specific/selective towards pathways related to sensory processing, mainly during REM sleep. Such an idea is corroborated by recent findings concerning the cognitive role of sleep. During REM sleep right after a motor learning, mice presented a synaptic pruning in the synapses that were ‘weakened’ during the task, while a little number of synapses were ‘strengthened
BANKING MEMBERS:
Interno - 1721223 - ADRIANO BRETANHA LOPES TORT
Externo à Instituição - CLEITON LOPES AGUIAR - UFMG
Interno - 1824636 - RICHARDSON NAVES LEAO
Presidente - 1660044 - SIDARTA TOLLENDAL GOMES RIBEIRO
Externo à Instituição - VINICIUS ROSA COTA - UFSJ
Interno - 051.724.194-38 - VITOR LOPES DOS SANTOS - UFRN