Neurological disorder | EPFL Graph Search

A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakness, poor coordination, loss of sensation, seizures, confusion, pain and altered levels of consciousness. There are many recognized neurological disorders, some relatively common, but many rare. They may be assessed by neurological examination, and studied and treated within the specialities of neurology and clinical neuropsychology. Interventions for neurological disorders include preventive measures, lifestyle changes, physiotherapy or other therapy, neurorehabilitation, pain management, medication, operations performed by neurosurgeons or a specific diet. The World Health Organization estimated in 2006 that neurological disorders and their s

Thalamic microcircuitry: neurons, synapses, and circuit motifs in receptive field structure and sensory processing

Jane Yi

Our perception of the world is first shaped by the thalamus, a structure composed of many nuclei in the center of our brains. Different nuclei hold different responsibilities - vision (dorsal lateral genicular nucleus; dLGN), audition (medial geniculate nucleus; MGN), somatosensation (ventro-basal nuclei; VB), though many properties across these sensory modalities appear to be universal. In this thesis, we completed a comprehensive characterization of the neurons, connections, and microcircuitries within the rodent VB thalamus. Our most prominent finding is the confirmation of the existence of local interneurons in the VB and the discovery of their profoundly active and diverse role in thalamic processes. Thus, we have observed that the fundamental excitatory and inhibitory neurons of dLGN and VB nuclei and their intrinsic circuit motifs are indistinguishable. Only a few notable differences are, however, present. (1), Principal excitatory neurons of the VB, the thalamocortical (TC) relays, have morphological types that appear to be distributed heteroge-neously throughout the VB whereas dLGN TC morphological types have regional preferences. (2), VB inhibitory local interneurons represent a smaller proportion of the total neuronal popula-tion compared to their dLGN counterparts. The similarities between these thalamic regions great-ly outnumber the differences. It then introduces new questions of how different vision and soma-tosensation of the physical world are when these senses are ultimately represented as binary sig-nals and are processed in similar manners in the thalamus. Following these questions may lead to new therapeutic solutions for retinally blind patients, tactile prostheses, or neurological disorders of sensory perception like schizophrenia.

EPFL2021

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

Cynthia Marchand

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

Natl Acad Sciences2015

Regulation of the protein complex NEEP21 - GRIP - GluR2 implicated in AMPAR trafficking through endosomal compartments

Karina Kulangara

It is important for neurotransmission to control the number of receptors at synapses. The synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type of glutamate receptors (AMPARs) control the strength of excitatory transmission. These receptors are mobile and cycle between internal endosomal compartments and the plasma membrane. We have identified previously a protein complex between the endosomal protein NEEP21, the AMPAR subunit GluR2 and the scaffold protein GRIP necessary for correct GluR2 recycling. Here we elucidate the regulation underlying the complex formation and dissociation necessary for the trafficking through endosomal compartments. We show that a 85 kDa protein kinase, which is associated with NEEP21, phosphorylates GRIP on serine 917. Protein kinase C is activated by glutamate receptor stimulation, and leads to the activation of the NEEP21-associated kinase. The phosphorylation of GRIP leads to a reduced binding between GRIP and NEEP21, and GRIP and GluR2. Serine 917 is implicated in AMPAR cycling, since a wildtype carboxyterminal GRIP fragment expressed in hippocampal neurons interferes with GluR2 surface expression. On the contrary, a S917D mutant fragment does not interfere with GluR2 surface expression. The regulation of the formation and dissociation of the protein complex between NEEP21, GluR2 and GRIP1 may suggest a sorting mechanism between the recycling and degradation pathways for the AMPAR subunit GluR2. This is especially important in the light of the discovery of a form of plasticity which implicates GluR2-lacking AMPAR, and the fact that insertion of GluR2-lacking AMPAR are implicated in a number of neurological diseases like ALS or ischemia. Our results identify an important regulatory mechanism in the trafficking of AMPAR subunits between internal compartments and the plasma membrane.

EPFL2006

Regulation of the protein complex NEEP21 - GRIP - GluR2 implicated in AMPAR trafficking through endosomal compartments

Karina Kulangara

EPFL2006