In multiple sclerosis, autoaggressive T cells cross the blood-brain barrier (BBB) and enter the CNS parenchyma promoting inflammation, demyelination and eventually neurodegeneration. T-cell diapedesis across the BBB can occur via a paracellular pathway across the endothelial junctions or via a transcellular pathway, through a pore across the endothelial cell body. However, the precise mechanisms underlying paracellular versus transcellular T-cell diapedesis across the BBB remain to be explored. Thus, the aim of the present study is to determine the subcellular structures formed during T-cell interaction with the BBB. To do so, we combined in vitro live cell imaging and serial block face scanning electron microscopy (SBF-SEM), to perform the analysis in a 3D ultrastructural level.
Talk 2: Nano-scale microfluidics to study 3D chemotaxis at the single cell level
Chemotaxis of immune cells plays an important role in immune surveillance and inflammation. The mode of migration depends highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. We have developed a microfluidic migration device which allows to study immune cell migration in a 3D collagen environment in highly controlled diffusion-based chemokine gradients.
Deep brain stimulation is an established treatment for Parkinson’s disease and other movement disorders. This therapy however is limited by the slow manual and error-prone programming algorithms to identify the optimal stimulation site and by the stimulation induced side-effects. Electrophysiological recordings from the basal ganglia, the structures where the electrodes are implanted, revealed the presence of electrophysiological markers related to the motor symptoms. Studying distribution and behavioral characteristics of these markers led to the first pilot studies toward automatized programming and closed-loop stimulation in Parkinson’s disease.
Talk 2: Towards closed-loop neuromodulation of brain and spinal circuits to alleviate gait and balance deficits in Parkinson's disease
Impairments of gait and balance are amongst the most incapacitating and least well-understood symptoms of Parkinson's disease (PD). Well-established neuromodulation therapies for PD, which are highly effective for the treatment of upper-limb motor signs, often exhibit modest results to alleviate gait deficits. This discrepancy is presumably due to the divergence in the nature and dynamics of the circuits that control leg versus upper limb movements.
To date, the brain signatures underlying leg motor function and dysfunction, their involvement in leg muscle recruitment and force modulation across locomotor activities, and their utility to help refine therapies remains unclear. Similarly, the impact of combining brain and spinal neuromodulation therapies to specifically address locomotor deficits remains controversial.
In this talk, I will present results on these two questions:
First, we aimed to identify the neural correlates of leg force modulation from local field potentials (LFPs) recorded from deep brain stimulation electrodes implanted in the subthalamic nucleus (STN) of patients with PD, and to leverage this framework to develop decoding algorithms able to automatically predict leg force intention in real-time.
Second, we employed brain-decoded intention to trigger and control spinal cord neuromodulation therapies during unconstrained movements in non-human primate model of PD.
These combined results confirm the capacity to leverage brain signals to decode force production and leg motor intention in real-time, and to further exploit them to provide personalised therapies of brain and spinal cord to address gait deficits.
We have identified a population of spinal cord inhibitory interneurons that are critical components of swim stress-induced analgesia, which are identified by the expression of the transcription factor Gbx1. These Gbx1-expressing interneurons are required for stress-induced analgesia but are not required for pain perception under normal conditions, and their activation is sufficient to produce a robust analgesia in all tested pain modalities. Spinal Gbx1-expressing neurons and the circuits that activate them represent potential targets for the treatment of chronic pain.
Talk 2: Neuronal network dynamics and sensory representation in the ACC
(Mario A. Acuña, Postdoc at Nevian lab, University of Bern)
Chronic pain affects to 20% of the European population; therefore, understanding the processes underlying such pain chronification is imperative. Accumulating evidence indicates that abnormal neuronal plasticity and a resulting hyperactivity of the anterior cingulate cortex (ACC) is the cause for the manifestation of the emotional distress that characterizes chronic pain conditions. However, how the functional organization of ACC neuronal microcircuits is affected in chronic pain is poorly understood. In this talk I will present the current advances we are making towards an understanding on how pain is represented in the mouse ACC using in-vivo 2-photon calcium imaging.
We show that GABAergic neurons in the lateral hypothalamus of mice simulataneously encode instantaneous feeding behavior and feeding history. Populations of feeding active neurons are activated during REM sleep and their silencing specifically durgin REM sleep but not wakefulness decreases subsequent food intake.
Talk 2: Basal forebrain contributions to brain state regulation during auditory learning and sleep
(Arndt-Lukas Klaassen, PhD student in the Rainer Lab, University of Fribourg)
The basal forebrain (BF) projections play an important role in modulating neural network states, for example by enhancing cortical responsivity as well as contributing to wake/sleep regulation. The BF projections regulate cerebral cortical function by providing the major source of cholinergic as well as GABA- and glutamatergic input to the neocortex. Here, we aim to investigate the neuromodulatory influence of the BF on brain state regulation by combining optogenetic stimulation in the ventral pallidum of the BF with electrophysiology in the anterior cingulate cortex (ACC) in rats.
Talk 1: From Psychologist, to Neuroscientist, to Scientific Officer
(Armand Mensen, Swiss 3RCC)
Armand will talk about his career path from obtaining his PhD, through his 6 year Post-doc career, and how he ended up as a Scientific Officer at the Swiss 3RCC, with a foot still in the door of the academic track... just in case.
Talk 2: From academia to a biotech startup
(Charles Finsterwald, GliaPharm)
GliaPharm is a Swiss biotech start-up company based in Geneva that develops innovative treatments against neurodegenerative disorders. GliaPharm’s therapeutic approach stems from pioneering work pursued for many years by Prof. Magistretti’s laboratory at EPFL (Lausanne). Based on the understanding of the role of glial cells in the course of neurodegenerative disorders, and the importance of the so-called astrocyte-neuron lactate shuttle (ANLS), GliaPharm is developing innovative therapeutic approaches by targeting those mechanisms.
GliaPharm was created in 2016 as a spinoff from EPFL, and moved one year later to the Campus Biotech in Geneva, where it has since been pursuing its drug development activities, currently at the preclinical stage. GliaPharm’s objective is to enter into clinical trials with its lead molecule by early 2022.
Dr. Charles Finsterwald is co-founder and the Chief Scientific Officer at GliaPharm. During his talk, Dr. Finsterwald will describe GliaPharm’s scope, therapeutic approach and history. He will also discuss his personal experience as a co-cofounder and working in a start-up company.