Quantum Mechanics of 'Conscious Energy'

This paper is aiming to investigate the physical substrate of conscious process. It will attempt to find out: How does conscious process establish relations between their external stimuli and internal stimuli in order to create reality? How does consciousness devoid of new sensory input result to its new quantum effects? And how does conscious process gain mass in brain? This paper will also try to locate the origins of consciousness at the level of neurons along with the quantum effects of conscious process

Neuroanatomical and Morphological Properties of Neurons that Generate Inspiratory Related Breathing Rhythm and Influence Respiratory Motor Pattern in Mice

The relationship between neuron morphology and function is a perennial issue in neuroscience. Information about synaptic integration, network connectivity, and the specific roles of neuronal subpopulations can be obtained through morphological analysis of key neurons within any given microcircuit. Breathing is essential behavior for humans and all mammals, yet the neural microcircuit that governs respiration is not completely understood. The respiratory neural microcircuit resides within the ventral respiratory column located in the medulla. Within the respiratory column, the site of respiratory rhythm generation is the bilaterally distributed preBötzinger complex (preBötC). Rhythm-generating neurons in the preBötC are derived from a single genetic line, i.e., precursor cells expressing the transcription factor Developing brain homeobox-1 (Dbx1). An analysis of over 40 dendritic morphological features of rhythmogenic Dbx1 preBötC neurons and putatively premotor Dbx1 neurons in the intermediate reticular formation, revealed these two populations are similar except reticular neurons have a larger dendritic diameter, which may contribute to a greater passive transmembrane conductance. Both populations showed commissural axon projections and reticular formation neurons show premotor-like projections to the XII motor nucleus. These morphological data provide additional evidence supporting bilateral synchronization the preBötC through Dbx1 neurons, and demonstrate that Dbx1 preBötC neuron connectivity includes recurrent interconnections. On the molecular level, the ion channels that mediate rhythm-generating whole-cell ion currents have not been not identified, and were investigated using principally an anatomical approach. The nonspecific cation current, ICAN, underlies robust inspiratory drive potentials in the preBötC and the persistent sodium current, INaP may play a role in the production of robust bursts when respiration is challenged in such cases as anoxia or hypoxia. The leading candidate for ion channels that contribute to ICAN belong to the transient membrane receptor (Trp) ion channel superfamily and the leading ion channel candidate for INaP is Nav1.6. I determined the presence of Trpc3 ion channels and Nav1.6 ion channels on Dbx1 preBötC neurons (as well as their expression in neighboring non-Dbx1 preBötC neurons). Finally, breathing behavior involves periodic sighs, which are slower than normal eupneic breathing but critical for lung function. I examined receptor expression for bomebsin-like peptides neuromedin B (NMB) and gastrin releasing peptide (GRP), which are important for sigh behavior. I show that NMB and GRP receptors are expressed in Dbx1 preBötC neurons and are not expressed by glia in the preBötC, as posited by some because of the low frequency of sigh breaths. These advances in morphological and anatomical knowledge can be used to design targeted in vitro and in vivo experiments to further explore their role in respiratory rhythm and pattern generation

Hallmarks of Alzheimer Disease are Evolving Relentlessly in Metropolitan Mexico City Infants, Children and Young Adults. APOE4 Carriers Have Higher Suicide Risk and Higher Odds of Reaching NFT Stage V at ≤ 40 Years of Age

Exposures to fine particulate matter (PM2.5) and ozone (O3) above USEPA standards are associated with Alzheimer’s disease (AD) risk. Metropolitan Mexico City (MMC) residents have life time exposures to PM2.5 and O3 above USEPA standards. We investigated AD intra and extracellular protein aggregates and ultrastructural neurovascular pathology in 203 MMC residents age 25.36±9.23y. Immunohistochemical methods were used to identify AT8 hyperphosphorilated tau (Htau) and 4G8 (amyloid β 17-24). Primary outcomes: staging of Htau and amyloid, per decade and cumulative PM2.5 (CPM 2.5) above standard. Apolipoprotein E allele 4 (APOE4), age and cause of death were secondary outcomes. Subcortical pretangle stage b was identified in an 11month old baby. Cortical tau pretangles, neurofibrillary tangles (NFT) Stages I-II, amyloid phases 1-2, Htau in substantia nigrae, auditory, oculomotor, trigeminal and autonomic systems were identified by the 2nd decade. Progression to NFT stages III-V was present in 24.8 % of 30-40y old subjects. APOE4 carriers have 4.92 times higher suicide odds (p=0.0006), and 23.6 times higher odds of NFT V (p \u3c 0·0001) v APOE4 non-carriers having similar CPM2.5 exposure and age. Age (p = 0.0062) and CPM2.5 (p = 0.0178) were significant for developing NFT V. Combustion-derived nanoparticles were associated with early and progressive damage to the neurovascular unit. Alzheimer’s disease starting in the brainstem of young children and affecting 99.5% of young urbanites is a serious health crisis. Air pollution control should be prioritised. Childhood relentless Htau makes a fundamental target for neuroprotective interventions and the first two decades are critical. We recommend the concept of preclinical AD be revised and emphasize the need to define paediatric environmental, nutritional, metabolic and genetic risk factor interactions of paramount importance to prevent AD. AD evolving from childhood is threating the wellbeing of our children and future generations

The Neuroanatomy of the Reticular Nucleus Locus Coeruleus in Alzheimer's Disease.

Alzheimer's Disease (AD) features the accumulation of β-amyloid and Tau aggregates, which deposit as extracellular plaques and intracellular neurofibrillary tangles (NFTs), respectively. Neuronal Tau aggregates may appear early in life, in the absence of clinical symptoms. This occurs in the brainstem reticular formation and mostly within Locus Coeruleus (LC), which is consistently affected during AD. LC is the main source of forebrain norepinephrine (NE) and it modulates a variety of functions including sleep-waking cycle, alertness, synaptic plasticity, and memory. The iso-dendritic nature of LC neurons allows their axons to spread NE throughout the whole forebrain. Likewise, a prion-like hypothesis suggests that Tau aggregates may travel along LC axons to reach out cortical neurons. Despite this timing is compatible with cross-sectional studies, there is no actual evidence for a causal relationship between these events. In the present mini-review, we dedicate special emphasis to those various mechanisms that may link degeneration of LC neurons to the onset of AD pathology. This includes the hypothesis that a damage to LC neurons contributes to the onset of dementia due to a loss of neuroprotective effects or, even the chance that, LC degenerates independently from cortical pathology. At the same time, since LC neurons are lost in a variety of neuropsychiatric disorders we considered which molecular mechanism may render these brainstem neurons so vulnerable

Reticulospinal and corticospinal axon regeneration after complete spinal cord injury

Neuroprosthetic rehabilitation demonstrated that significant functional benefit could be achieved with lumbosacral neuromodulation in both human and animal models of spinal cord injury. It promoted the recovery of voluntary leg movements through the reorganization of residual reticulospinal and propriospinal projections pathways. However, in case of complete spinal cord injuries (SCI), which isolate the circuits under the lesion from any supraspinal control, the outcome of neuroprosthetic rehabilitation is still not sufficient. Indeed, it will require the restoration of robust regrowth and sprouting of several types of axons across the injury. Axons fail to regrow across spinal lesions because of different inhibitory mechanisms. It has been demonstrated that this spontaneous axon regeneration failure can be reversed by i) stimulating the neuronal intrinsic growth capacity using viral technology, ii) remodeling the lesion core with growth factors, in order to create a more permissive environment, and iii) guiding axons with chemo-attractive molecules across and beyond the SCI site. It was thus demonstrated that propriospinal axons are able to regrow and build a robust descending bridge across complete SCIs when the needed facilitators are provided. However, this robust propriospinal bridging failed to promote functional recovery by itself. It might be explained by an insufficient descending motor control partly supported by other systems such as the reticulospinal tract (RtST) and the corticospinal tract (CST). Therefore we wanted to study the regenerative potential of the RtST and CST pathways. The RtST arises from the brainstem and reaches for the spinal cord acting as relay for descending motor cortical commands. The CST is the main descending motor cortical command arising from the primary motor cortex. In the present study, we applied the same strategy to enhance sprouting and regrowth of reticulospinal and corticospinal neurons across anatomically complete SCI. We first activated the neuronal intrinsic growth capacity of both tracts using viral technology. The lesion environment was then remodeled with growth factors, delivered using a biocompatible hydrogel. Finally, we established chemical axon guidance using chemoattractant molecules. These interventions were delivered with a spatiotemporal profile corresponding to the axon growth sequence during development. We did not obtain any CST regeneration, due to the severe crush injury model inducing extensive CST axons degeneration probably caused by ischemic phenomenon. Regarding the RtST, we obtained significant reticulospinal regeneration into the lesion core with some fibers growing across the lesion reaching the healthy caudal tissue. This regeneration remained limited though as compared with the propriospinal results indicating the importance of identifying complementary strategies to increase the density of the regenerated tract and to attract the axons in the healthy tissue below the SCI. Our ultimate goal is to restore anatomical communications across complete SCI and promote their functional integration using neuroprosthetic rehabilitation program

Glycinergic input to the mouse basal forebrain cholinergic neurons

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Developmental hypomyelination in Wolfram syndrome: New insights from neuroimaging and gene expression analyses

Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging studies showed marked alteration in early brain development, primarily characterized by abnormal white matter myelination. Interestingly, ER stress and the UPR pathway are implicated in the pathogenesis of some inherited myelin disorders like Pelizaeus-Merzbacher disease, and Vanishing White Matter disease. In addition, exploratory gene-expression network-based analyses suggest that WFS1 expression occurs preferentially in oligodendrocytes during early brain development. Therefore, we propose that Wolfram syndrome could belong to a category of neurodevelopmental disorders characterized by ER stress-mediated myelination impairment. Further studies of myelination and oligodendrocyte function in Wolfram syndrome could provide new insights into the underlying mechanisms of the Wolfram syndrome-associated brain changes and identify potential connections between neurodevelopmental disorders and neurodegeneration

Review: Neuropathology findings in autonomic brain regions in SUDEP and future research directions

Autonomic dysfunction is implicated from clinical, neuroimaging and experimental studies in sudden and unexpected death in epilepsy (SUDEP). Neuropathological analysis in SUDEP series enable exploration of acquired, seizure-related cellular adaptations in autonomic and brainstem autonomic centres of relevance to dysfunction in the peri-ictal period. Alterations in SUDEP compared to control groups have been identified in the ventrolateral medulla, amygdala, hippocampus and central autonomic regions. These involve neuropeptidergic, serotonergic and adenosine systems, as well as specific regional astroglial and microglial populations, as potential neuronal modulators, orchestrating autonomic dysfunction. Future research studies need to extend to clinically and genetically characterized epilepsies, to explore if common or distinct pathways of autonomic dysfunction mediate SUDEP. The ultimate objective of SUDEP research is the identification of disease biomarkers for at risk patients, to improve post-mortem recognition and disease categorisation, but ultimately, for exposing potential treatment targets of pharmacologically modifiable and reversible cellular alterations

The sea lamprey GABAB receptor. Changes after spinal cord injury and its role in axonal regeneration

Spinal cord injury (SCI) causes irreversible loss of function. In contrast to mammals, lampreys show an amazing capacity for spontaneous recovery after a complete SCI. They provide an interesting model to understand the molecular processes that lead to spontaneous recovery. In this study, we analysed the changes in the expression of both gabab subunits after a complete SCI. Our results showed that plastic changes in this system probably contribute to the recovery of function after SCI in lampreys. Pharmacological and genetic manipulations revealed that endogenous GABA acting through GABAB receptors promotes axonal regeneration of descending neurons after a complete SCI in lampreys