In search of consciousness: Examining the temporal dynamics of conscious visual perception using MEG time-series data.

The mere presence of information in the brain does not always mean that this information is available to consciousness. Experiments using paradigms such as binocular rivalry, visual masking, and the attentional blink have shown that visual information can be processed and represented by the visual system without reaching consciousness. Using multivariate pattern analysis (MVPA) and magneto-encephalography (MEG), we investigated the temporal dynamics of information processing for unconscious and conscious stimuli. We decoded stimulus information from the brain recordings while manipulating visual consciousness by presenting stimuli at threshold contrast in a backward masking paradigm. Participants' consciousness was measured using both a forced-choice categorisation task and self-report. We show that brain activity during both conscious and non-conscious trials contained stimulus information and that this information was enhanced in conscious trials. Overall, our results indicate that visual consciousness is characterised by enhanced neural activity representing the visual stimulus and that this effect arises as early as 180 ms post-stimulus onset.

Genetic or pharmacological depletion of cannabinoid CB1 receptor protects against dopaminergic neurotoxicity induced by methamphetamine in mice.

Accumulating evidence suggests that cannabinoid ligands play delicate roles in cell survival and apoptosis decisions, and that cannabinoid CB1 receptors (CB1R) modulate dopaminergic function. However, the role of CB1R in methamphetamine (MA)-induced dopaminergic neurotoxicity in vivo remains elusive. Multiple high doses of MA increased phospho-ERK and CB1R mRNA expressions in the striatum of CB1R (+/+) mice. These increases were attenuated by CB1R antagonists (i.e., AM251 and rimonabant), an ERK inhibitor (U0126), or dopamine D2R antagonist (sulpiride). In addition, treatment with MA resulted in dopaminergic impairments, which were attenuated by CB1R knockout or CB1R antagonists (i.e., AM251 and rimonabant). Consistently, MA-induced oxidative stresses (i.e., protein oxidation, lipid peroxidation and reactive oxygen species) and pro-apoptotic changes (i.e., increases in Bax, cleaved PKCδ- and cleaved caspase 3-expression and decrease in Bcl-2 expression) were observed in the striatum of CB1R (+/+) mice. These toxic effects were attenuated by CB1R knockout or CB1R antagonists. Consistently, treatment with four high doses of CB1R agonists (i.e., WIN 55,212-2 36mg/kg and ACEA 16mg/kg) also resulted in significant oxidative stresses, pro-apoptotic changes, and dopaminergic impairments. Since CB1R co-immunoprecipitates PKCδ in the presence of MA or CB1R agonists, we applied PKCδ knockout mice to clarify the role of PKCδ in the neurotoxicity elicited by CB1Rs. CB1R agonist-induced toxic effects were significantly attenuated by CB1R knockout, CB1R antagonists or PKCδ knockout. Therefore, our results suggest that interaction between D2R, ERK and CB1R is critical for MA-induced dopaminergic neurotoxicity and that PKCδ mediates dopaminergic damage induced by high-doses of CB1R agonist.