Past events

Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) in brown Norway rats mimicks neurodegenerative aspects of multiple sclerosis (MS). In this model, optic neuritis leads to acute axonal lesions and consecutive apoptotic cell death of RGCs, whose axons form the optic nerve. The intracellular mechanisms of RGC apoptosis resemble those described after surgical transection of the optic nerve. These mechanisms involve shifts in the expression of Bcl-2 family members, mitogen-activated protein kinases , and the phosphatidylinositol-3-kinase/Akt pathway. Current research on neurodegenerative aspects in EAE or MS is focused on developing treatment strategies that inhibit degeneration of axons as well as protection of the neuronal cell body from apoptotic cell death. The concept of achieving neuroprotective effects by successful treatment of inflammation and autoimmunity was supported by studies showing a close association of axonal damage and inflammation. However, trials evaluating anti-inflammatory therapies in MS patients have shown that elimination of the inflammatory component of the disease does not necessarily stop progression of brain and spinal cord atrophy. Methylprednisolone, the standard treatment of autoimmune optic neuritis, accelerates visual recovery, but it does not influence the final visual outcome. In MOG-induced optic neuritis, even detrimental effects of anti-inflammatory treatment with methylprednisolone on the survival of RGCs were observed. On the other hand, blocking apoptosis signals in neurons without simultaneously treating inflammation-induced axon degeneration does not lead to functionally relevant results: Although application of Epo as well as CNTF increases survival rates of RGCs during MOG-induced optic neuritis, visual acuity in these animals remains poor due to severe and ongoing degeneration of optic nerve axon fibers. These observations led to a hypothesis that can easily be transferred to the situation in MS: Due to the much larger proportion of white matter in the human brain, preventing apoptosis of neuronal cell bodies alone might not find its expression in clinical scores and neurological function. Therefore, neuroprotective approaches in combination with the established disease-modifying therapies might be more promising. Simultaneous application of methylprednisolone and Epo or Minocycline in MOG-induced optic neuritis resulted in a functional, electrophysiological improvement of optic nerves and RGCs as well as in increased neuronal and axonal survival The lecture will outline the transfer of these experimental approaches into a clinical trial and discuss other new neuroprotective and regenerative strategies.

Stress related dissorders are likely to result from atypical processing and integration of information by several serieses of neural networks. These dissorders have been associated with neuroadaptations found at molecular and cellular levels within reward-related brain regions. The nucleus accumbens (NAcc) is a central component of the reward system. Convergence of glutamatergic innervations from limbic and cortical structures under intense dopaminergic modulations, places the NAcc as the major site for integration of emotional salience, contextual constraints and executive/motor plans. In the current study we found the medial shell of the NAcc to exhibit life-experience dependant adaptations. In animals exposed to chronic mild stress (CMS), there was an increase in spontaneous patterned network activity, synaptic potentiation of vSub innervations and increased GluR1 levels in the NAcc shell. In contrast, the ability to sustain time-locked, hippocampally evoked, network response was strongly reduced. That and more, we found evidence for short- and long- term plasticity in the vSub-NAcc pathway of CMS animals, but not in their control counterparts. Over all, we argue that stressful life-experience is associated with in-vivo, long-term functional adaptations in the reward system. The individual animal’s life experience history was found to leave its mark on the NAcc network activity, properties and response. Taken together with the life-experience dependent plasticity results, these adaptations are suggested to reflect part of the adverse functional mechanism which guide behavioral deficits in stress related dissorders.

Abstract: In many regions of the brain, neurons form an ordered representation of the outside world. For example, the 'homunculus' of the somatosensory cortex is a point-to-point topographic map of the body surface onto the brain surface. The spatially organized convergence of sensory inputs often leads to similar response properties in target neurons that are in close vicinity. Whether their individual information content is redundant or independent depends on the circuit architecture (the interplay between common input, lateral signals and feedback from other brain areas) and the computational goals of the network. In the mammalian olfactory bulb (OB), sensory neurons expressing the same type of olfactory receptor (~10,000) converge in tight focus, forming clusters of synapses called glomeruli (~2,000). From each glomerulus, a few dozen mitral cells (principal output neurons of the OB) carry the output further to the cortex. The mitral cells, typically have only one primary dendrite that projects to a single glomerulus, but can sample inputs on their primary and secondary dendrites from functionally diverse glomeruli via several types of interneurons. Thus, a few dozen mitral cells share input from the same parent glomerulus, but may have different inhibitory surrounds. In the first part of this talk, I will discuss the topographic layout of glomeruli on the bulb - the olfactory map. How precise is this map within and across two species: mouse and rat? How does its structure relate to odor processing? Do glomeruli that are responsive to structurally similar odor molecules have a tendency to lie next to each other? In other words, is there a chemotopic map? In the second part of the talk, I will focus on probing the odor response properties of mitral cells using extracellular recordings and an optogenetic strategy to ask whether the OB is more than a relay station. Do mitral cells receiving common input from the same parent glomerulus carry redundant information about odors to cortex? I will conclude by describing novel strategies that allow monitoring the input-output transfer function of the OB via multi-photon microscopy imaging of bulb neurons activity in the same animal, in different states of the circuit. Link for further information: http://www.cshl.edu/public/SCIENCE/albeanu.html