Past events

Since the first recordings made of evoked action potentials it has become apparent that the responses of individual neurons to ongoing physiologically relevant input, are highly variable. This variability is manifested in non-stationary behavior of practically every observable neuronal response feature. We introduce the Neuronal Response Clamp, a closed-loop technique enabling full control over two important single neuron activity variables: response probability and stimulus-spike latency. The technique is applicable over extended durations (up to several hours), and is effective even on the background of ongoing neuronal network activity. The Response Clamp technique is a powerful tool, extending the voltage-clamp and dynamic-clamp approaches to the neuron's functional level, namely-its spiking behavior.

Synchronized firing of mitral cells in the olfactory bulb, the first relay station of the olfactory system, has been hypothesized to convey information to olfactory cortex. In this first survey of synchronized firing by mitral cells in awake behaving vertebrates, we find sparse divergent odor responses. Surprisingly, synchronized firing conveys information on odor value (is it rewarded?) rather than odor quality. Further, adrenergic block decreases the magnitude of odor divergence of synchronous firing. These data raise questions whether mitral cells contribute to decision-making, or convey expected outcomes used in prediction error calculation.

As a rat runs through a familiar environment, the hippocampus retrieves a previously stored spatial representation of the environment. When the environment is modified a new representation is seen, presumably corresponding to the hippocampus encoding the new information. I will present single unit data and discuss how the “hippocampus decides” whether to retrieve an old representation or form a new representation.

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.