This review provides an overview of the current understanding of the neural systems involved in regulating wakefulness, non-rapid eye movement sleep (NREMS), and rapid eye movement sleep (REMS) in mammals. Specifically, we focus on the anatomical connections between the subiculum, a component of the hippocampal formation, and the regions responsible for regulating the sleep-wake cycle. The subiculum exhibits direct connections with key areas involved in sleep regulation, such as the lateral hypothalamus, tuberomammillary nucleus, basal forebrain, ventrolateral preoptic nucleus, ventrolateral tegmental area, and suprachiasmatic nucleus. Additionally, second-order projections from the subiculum are received by the laterodorsal tegmental nucleus and locus coeruleus, suggesting potential involvement of the subiculum in the regulation of circadian rhythms, particularly the circadian sleep-wake cycle. We also discuss alterations in the subiculum observed in individuals with sleep disorders and sleep-deprived mice, underscoring the significance of investigating neuronal communication between the subiculum and pathways promoting both sleep and wakefulness.

Sleep disturbances very common in children with autism. That is why it requires instruments that facilitate its evaluation. Goals: Perform the evaluation of sleep from a subjective prospect in a group of children with primary autism and compare to a control group, using the Sleep Habits in Children Survey (CSHQ), In order to determine sleep disturbances, according to the sub-scales results. Method: A prospective cross-sectional study of the sample was carried out. A group with primary Autism n = 21 was selected. For the assessment of the dream we chose (CSHQ). The differences between independent groups were calculated by applying a Mann Whitney U test (p <0.05). Results: The group of children with autism showed the highest values of the total scale (mean = 48.00) wish is congruent with a greate disfuntion of sleep, compared to the control group (mean = 36.47) for p = 0.00. Significant differences were found for all sub scales p = 0.00, with the exception of sub-scale number 7. Conclusions: There is a high presence of sleep disturbances in children with primary autism, which are related to multifactorial causes, with the exception of sleep breathing disorders that did not show statistically significant differences between groups.

Sleep is still considered a mystery, despite intense scientific investigation. Here we present the first complete biological theory of sleep. The role of sleep is to restore the optimal homeostatic state, which is essential for tissue performance and health. Non-rapid eye movement sleep (NREMS) restores cortical and most other brain neurons, via relaxed global activity managed by thalamocortical circuits. The role of REM sleep is to restore acetylcholine (ACh) neurons, which support focused responses and hence cannot participate in global oscillations. Sleep enhances learning and memory via state restoration and ACh-affected paths. NREMS induces a lack of consciousness because global synchronous activity prevents focused responses, which are essential for consciousness. Dreams result from focused neural firing during sharp-wave ripples and REMS, and have a sense of reality because they involve the same neurons representing focused perceptual responses during wake. Anesthetics utilize a variety of mechanisms that prevent focused responses.

Three types of wakefulness appeared along the vertebrate’s phylogeny and ontogeny: spinal-rhombencephalic in fish, brainstem-diencephalic in reptiles and cortical in mammals, in which the paralyzed spinal-rhombencephalic wake and the brainstem-diencephalic wake remain as REMS and NREMS The spinal-rhombencephalic and cortical types of wake are inherently anti-homeostatic. Animals must forage, reproduce, and survive to predation disregarding the environmental circumstances, hence temporarily forgetting the homeostatic regulation. After fulfilling the vital functions, the brainstem-diencephalic wake recovers the homeostatic control. The phasic signs of REMS are adaptive in immature mammals, serving for demanding heat, milk and defense to their mother. These advantages outweigh the REMS' poikilostasis in infants. The adults’ poikilostasis of REMS is harmless in thermoneutral environments but is mal-adaptive in aquatic environments in which REMS is reduced or even disappears. These exceptions explain the anomalous examples of REMS. An on-off hypothalamic switch homeostatically regulates the entrance and exit from REMS. Furthermore, the vital phasic signs of REMS depend on a second pontine proportional homeostatic control. Altogether, they regulate the expression of REMS.

When we are asleep we lose the ability to promptly respond to external stimuli and yet we spend many hours every day in this inherently risky behavioral state. This simple fact strongly suggests that sleep must serve essential functions that rely on the brain going offline, on a daily basis, and for long periods of time. If these functions did not require partial sensory disconnection, it would be difficult to explain why they are not performed during waking. Paradoxically, despite its central role in defining sleep and what sleep does, sensory disconnection during sleep remains a mystery. We have a limited understanding of how it is implemented along the sensory pathways, we do not know whether the same mechanisms apply to all sensory modalities, nor do we know to which extent these mechanisms are shared between non-rapid eye movement (NREM) sleep and REM sleep. The main goal of this contribution is to review some knowns and unknowns about sensory disconnection during sleep as a first step to fill this gap.

Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD. We compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score &gt;5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45-7.93), SNCA_A53T_rs104893877 (8.21, 2.26-36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08-4.10), and ZNF184_rs9468199 (1.89, 1.08-3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15-0.78). The ML algorithms led to similar results. The predictive models were highly specific (95-99%) but lacked sensitivity (9-39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop RBD in PD. Additional investigations are needed.

Through the use of a simplified model of consciousness this paper illustrates the symptoms of schizophrenia linked to neocortical structures and functions. It makes the case that the bewildering and varied presentation of symptoms in schizophrenia can be analyzed and explained using such models. The model is used to illustrate the central thesis of the paper, that schizophrenia is a disorder of neurogenesis which leads to progressive neurochemical, functional and neurophysiological changes that create the characteristic behaviors of the disease.

Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).

One of the major unsolved mysteries of biological science concerns the question of where and in what form information is stored in the brain. I propose that memory is stored in the brain in a mechanically encoded binary format written into the conformations of proteins found in the cell-extracellular matrix adhesions that organise each and every synapse. The MeshCODE framework outlined here represents a unifying theory of data storage in animals, providing read-write storage of both dynamic and persistent information in a binary format. Mechanosensitive proteins that contain force-dependent switches can store information persistently, which can be written or updated using small changes in mechanical force. These mechanosensitive proteins, such as talin, scaffold each synapse, creating a meshwork of switches that together form a code, the so-called MeshCODE. Large signalling complexes assemble on these scaffolds as a function of the switch patterns and these complexes would both stabilise the patterns and coordinate synaptic regulators to dynamically tune synaptic activity. Synaptic transmission and action potential spike trains would operate the cytoskeletal machinery to write and update the synaptic MeshCODEs, thereby propagating this coding throughout the organism. Based on established biophysical principles, such a mechanical basis for memory would provide a physical location for data storage in the brain, with the binary patterns, encoded in the information-storing mechanosensitive molecules in the synaptic scaffolds, and the complexes that form on them, representing the physical location of engrams. Furthermore, the conversion and storage of sensory and temporal inputs into a binary format would constitute an addressable read-write memory system, supporting the view of the mind as an organic supercomputer.

The movement toward prevention trials in people at-risk for Parkinson’s is rapidly becoming a reality. The authors of this article include a genetically at-risk advocate with the LRRK2 G2019S variant and two patients with rapid eye movement sleep behavior disorder (RBD), one of whom has now been diagnosed with Parkinson’s disease (PD). These authors participated as speakers, panelists, and moderators in the “Planning for Prevention of Parkinson’s: A Trial Design Forum” hosted by Massachusetts General Hospital in 2021 and 2022. Other authors include a young onset person with Parkinson’s (PwP) and retired family physician, an expert in patient engagement in Parkinson’s, and early career and veteran movement disorders clinician researchers. Several themes emerged from the at-risk participant voice concerning the importance of early intervention, the legitimacy of their input in decision-making, and the desire for transparent communication and feedback throughout the entire research study process. Challenges and opportunities in the current environment include lack of awareness among primary care physicians and general neurologists about PD risk, legal and psychological implications of risk disclosure, limited return of individual research study results, and undefined engagement and integration of individuals at-risk into the broader Parkinson’s community. Incorporating the perspectives of individuals at-risk as well as those living with PD at this early stage of prevention trial development is crucial to success.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) proteins are a diverse and evolutionarily conserved family of cytidine deaminases that provide a variety of functions from tissue-specific gene expression and immunoglobulin diversity to control of viruses and retrotransposons. APOBEC family expansion has been documented among mammalian species, suggesting a powerful selection for their activity. Enzymes with a duplicated zinc-binding domain often have catalytically active and inactive domains, yet both have antiviral function. Although APOBEC antiviral function was discovered through hypermutation of HIV-1 genomes lacking an active Vif protein, much evidence indicates that APOBECs also inhibit virus replication through mechanisms other than mutagenesis. Multiple steps of the viral replication cycle may be affected, although nucleic acid replication is a primary target. Packaging of APOBECs into virions was first noted with HIV-1, yet is not a prerequisite for viral inhibition. APOBEC antagonism may occur in viral producer and recipient cells. Signatures of APOBEC activity include G-to-A and C-to-T mutations in a particular sequence context. The importance of APOBEC activity for viral inhibition is reflected in the identification of numerous viral factors, including Vif, which are dedicated to antagonism of these deaminases. Such viral antagonists often are only partially successful, leading to selection for viral variants.

The study examined eating timing, diet, and the ratio of sleep phases in people with social jetlag (SJL). The study involved 83 participants who filled out a questionnaire, and 21 of them took part in the study of sleep phases by electroencephalography during the week. SJL was associated with a higher incidence rate of eating jetlag, eating phase delays, an increase in calorie intake after 9 p.m., a decrease in dietary fiber intake for breakfast, and melatonin-containing product consumption for dinner. Young people with SJL had a reduction in total sleep and light sleep phase duration by 60 and 36 min on work/school days and an increase in total sleep and REM sleep phase duration by 66 and 60 min on weekends, respectively. Young people consuming foods with more than 4234.5 ng of melatonin for dinner, compared with their peers consuming less than 313.2 ng of melatonin, showed a decrease in SJL and sleep debt by 54 and 90 min and an increase in the total sleep and the deep sleep phase duration by 66 and 30 min, respectively. Thus, the consumption of melatonin-containing foods for dinner is associated with a decrease in circadian misalignment and a sleep quality improvement.