A roadmap to integrate astrocytes into Systems Neuroscience.

Systems neuroscience is still mainly a neuronal field, despite the plethora of evidence supporting the fact that astrocytes modulate local neural circuits, networks, and complex behaviors. In this article, we sought to identify which types of studies are necessary to establish whether astrocytes, beyond their well-documented homeostatic and metabolic functions, perform computations implementing mathematical algorithms that sub-serve coding and higher-brain functions. First, we reviewed Systems-like studies that include astrocytes in order to identify computational operations that these cells may perform, using Ca2+ transients as their encoding language. The analysis suggests that astrocytes may carry out canonical computations in a time scale of subseconds to seconds in sensory processing, neuromodulation, brain state, memory formation, fear, and complex homeostatic reflexes. Next, we propose a list of actions to gain insight into the outstanding question of which variables are encoded by such computations. The application of statistical analyses based on machine learning, such as dimensionality reduction and decoding in the context of complex behaviors, combined with connectomics of astrocyte-neuronal circuits, is, in our view, fundamental undertakings. We also discuss technical and analytical approaches to study neuronal and astrocytic populations simultaneously, and the inclusion of astrocytes in advanced modeling of neural circuits, as well as in theories currently under exploration such as predictive coding and energy-efficient coding. Clarifying the relationship between astrocytic Ca2+ and brain coding may represent a leap forward toward novel approaches in the study of astrocytes in health and disease

Excitable Media Seminar

The simulation data presented here, and the conceptual framework developed for their interpretation are, both, in need of substantial refinement and extension. However, granting that they are initial pointers of some merit, and elementary indicators of general principles, several implications follow: the activity patterns of neurons and their assemblies are\ud interdependent with the extracellular milieu in which they are embedded, and to whose time varying composition they contribute. The complexity of this interdependence in the temporal dimension forecloses any time and context invariant relation between what the experimenter may consider stimulus input and its representation in neural activity. Hence, ideas of coding by (quasi)-digital neurons are called in question by the mutual interdependence of neurons and their\ud humoral milieu. Instead, concepts of 'mass action' in the Nervous system gain a new perspective: this time augmented by including the chemical medium surrounding neurons as part of the dynamics of the system as a whole. Accordingly, a meaningful way to describe activity in a neuron assembly would be in terms of a state space in which it can move along an infinite number of trajectories.\u

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

Possible Effects of Synaptic Imbalances on Oligodendrocyte–Axonic Interactions in Schizophrenia: A Hypothetical Model

A model of glial–neuronal interactions is proposed that could be explanatory for the demyelination identified in brains with schizophrenia. It is based on two hypotheses: (1) that glia–neuron systems are functionally viable and important for normal brain function, and (2) that disruption of this postulated function disturbs the glial categorization function, as shown by formal analysis. According to this model, in schizophrenia receptors on astrocytes in glial–neuronal synaptic units are not functional, loosing their modulatory influence on synaptic neurotransmission. Hence, an unconstrained neurotransmission flux occurs that hyperactivates the axon and floods the cognate receptors of neurotransmitters on oligodendrocytes. The excess of neurotransmitters may have a toxic effect on oligodendrocytes and myelin, causing demyelination. In parallel, an increasing impairment of axons may disconnect neuronal networks. It is formally shown how oligodendrocytes normally categorize axonic information processing via their processes. Demyelination decomposes the oligodendrocyte–axonic system making it incapable to generate categories of information. This incoherence may be responsible for symptoms of disorganization in schizophrenia, such as thought disorder, inappropriate affect and incommunicable motor behavior. In parallel, the loss of oligodendrocytes affects gap junctions in the panglial syncytium, presumably responsible for memory impairment in schizophrenia

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

Persons Versus Brains: Biological Intelligence in Human Organisms

I go deep into the biology of the human organism to argue that the psychological features and functions of persons are realized by cellular and molecular parallel distributed processing networks dispersed throughout the whole body. Persons supervene on the computational processes of nervous, endocrine, immune, and genetic networks. Persons do not go with brains

Developing a Device to Investigate Migration of Axon Through a Fibrotic Scar

Peripheral neural degenerative injuries lead to the formation of fibrotic scars at the site of the lesion which limits axonal regeneration. This project aims to investigate axonal extension through these fibrotic scars by constructing a device with PDMS and nitrocellulose membrane was designed to simulate the site of injury with a fibrotic scar. NIH 3T3 cells were seeded onto the nitrocellulose membrane to simulate the fibrotic scar. This scar was treated FGF2 in order to create a less dense extracellular matrix composition. The device was successful in replicating the environment of a peripheral nerve injury but provided inconclusive results. The validation of the individual parameters of the device suggest future use of treated fibrotic scar in overcoming axonal injuries

Developing a Device to Investigate Migration of Axon Through a Fibrotic Scar

Peripheral neural degenerative injuries lead to the formation of fibrotic scars at the site of the lesion which limits axonal regeneration resulting in loss of motor and sensory functionality. This project aims to investigate axonal extension through these fibrotic scars. In order to accomplish this, a device of PDMS and nitrocellulose membrane was designed to simulate the site of injury with a fibrotic scar. Fibroblast NIH 3T3 cells were seeded onto the nitrocellulose membrane to simulate the fibrotic scar. This scar was treated Fibroblast Growth Factor 2 (FGF2) in order to create a less dense extracellular matrix composition. To avoid unwanted fibroblast interaction with the neuron culture, the scar was decellularized before implementation into the device