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Studies aimed at neurological drug discovery have been carried out both in vitro and in vivo. In vitro cell culture models have showed potential as drug testing platforms characterized by high throughput, low cost, good reproducibility and ease of handling and observation. However, in vitro neuronal culture models are facing challenges in replicating in vivo-like activity patterns. This work reports an in vitro culture technique that is capable of producing micro three-dimensional (μ3D) cultures of only a few tens of neurons. The μ3D cultures generated by this method were uniform in size and density of neurons. These μ3D cultures had complex spontaneous synchronized neuronal activity patterns which were similar to those observed in the developing cortex and in much larger 3D cultures, but not in 2D cultures. Bursts could be reliably evoked by stimulation of single neurons. Synchronized bursts in μ3D cultures were abolished by inhibitors of glutamate receptors, while inhibitors of GABAA receptors had a more complex effect. This pharmacological profile is similar to bursts in neonatal cortex. Since large numbers of reproducible μ3D cultures can be created and observed in parallel, this model of the developing cortex may find applications in high-throughput drug discovery experiments.Total sleep deprivation (TSD) negatively affects cognitive function. Previous research has focused on individual variation in cognitive function following TSD, but we know less about how TSD influences the lateralization of spatial working memory. This study used event-related-potential techniques to explore asymmetry in spatial-working-memory impairment. Fourteen healthy male participants performed a two-back task with electroencephalogram (EEG) recordings conducted at baseline and after 36 h of TSD. We selected 12 EEG points corresponding to left and right sides of the brain and then observed changes in N2 and P3 components related to spatial working memory. Before TSD, P3 amplitude differed significantly between the left and right sides of the brain. This difference disappeared after TSD. Compared with baseline, P3 amplitude decreased for a duration as extended as the prolonged latency of N2 components. After 36 h of TSD, P3 amplitude decreased more in the right hemisphere than the left. We therefore conclude that TSD negatively affected spatial working memory, possibly through removing the right hemisphere advantage.Age-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries among people over 60 years. It has multiple triggers and risk factors, but despite intense research efforts, its pathomechanisms are currently not completely understood. AMD pathogenesis is characterized by soft drusen in Bruch's membrane and involves the retinal pigment epithelium-Bruch's membrane-choroid complex and adjacent structures, like photoreceptors. This study explores the potential of novel cultivation techniques to preserve photoreceptors in retinal explants to gain better insights in AMD pathology. The porcine retina explants were cultured for 4 and 8 days using three different explantation techniques, namely, control (photoreceptors facing down, touching the filter), filter (photoreceptors facing up, turned sample using a filter), and tweezers (photoreceptors facing up, turned sample using tweezers). Optical coherence tomography revealed that the tweezers method had the best capacity to limit thiising one. Due to the high homology of the porcine to the human retina, it provides a reasonable alternative to in vivo rodent models. Consequently, an adapted coculture system based on the current findings may serve as an ex vivo model suitable to analyze AMD pathomechanisms and novel therapeutic approaches.Circadian rhythm misalignment has a deleterious impact on the brain and the body. In rats, exposure to a 21-hour day length impairs hippocampal dependent memory. Sleep, and particularly K-complexes and sleep spindles in the cortex, have been hypothesized to be involved in memory consolidation. Altered K-complexes, sleep spindles, or interaction between the cortex and hippocampus could be a mechanism for the memory consolidation failure but has yet to be assessed in any circadian misalignment paradigm. In the current study, continuous local field potential recordings from five rats were used to assess the changes in aspects of behavior and sleep, including wheel running activity, quiet wakefulness, motionless sleep, slow wave sleep, REM sleep, K-complexes and sleep spindles, in rats exposed to six consecutive days of a T21 light-dark cycle (L9D12). Except for a temporal redistribution of sleep and activity during the T21, there were no changes in period, or total amount for any aspect of sleep or activity. These data suggest that the memory impairment elicited from 6 days of T21 exposure is likely not due to changes in sleep architecture. It remains possible that hippocampal plasticity is affected by experiencing light when subjective circadian phase is calling for dark. However, if there is a reduction in hippocampal plasticity, changes in sleep appear not to be driving this effect.The heterogeneous phenomenology of autism together with diverse patterns of comorbidities led in the past to formulation of manifold theories and hypotheses on different explanatory levels. click here We scrutinize most recent findings from genetics, neurobiology and physiology and derive testable hypotheses about possible physiological links between domains. With focus on altered sensory perception and neuronal processing in ASD, we assume two intertwined regulatory feedback circuits under the umbrella of genetics and environmental factors. Both regulatory circuits are highly variable between individuals in line with the heterogeneous spectrum of ASD. The circuits set off from altered pathways and connectivity in ASD, fueling HPA-axis activity and distress. In the first circuit altered tryptophan metabolism leads to higher neurotoxic substances and reinforces the excitationinhibition imbalance in the brain. The second circuit focuses on the impact and interaction with the environment and its rhythms in ASD. With lower melatonin levels, as the pacemaker molecule of the circadian system, we assume misalignment to outer and inner states corroborated from the known comorbidities in ASD.