In a famous philosophical paradox, Buridan's ass perishes because he is equally hungry and thirsty, and cannot make up his mind whether to first drink or eat. We are faced daily with the need to pick between alternatives that are equally attractive (or not) to us. What are the processes that allow us to avoid paralysis and to rapidly select between such equal options when there are no preferences or rational reasons to rely on? One solution that was offered is that although on a higher cognitive level there is symmetry between the alternatives, on a neuronal level the symmetry does not maintain. What is the nature of this asymmetry of the neuronal level? In this talk I will present experiments addressing this important phenomenon using measures of human behavior, EEG, EMG and large scale neural network modeling, and discuss mechanisms involved in the process of intention formation and execution, in the face of alternatives to choose from. Specifically, I will show results revealing the temporal dynamics of rapid intention formation and, moreover, ‘change of intention’ in a free choice picking scenario, in which the alternatives are on a par for the participant. The results suggest that even in arbitrary choices, endogenous or exogenous biases that are present in the neural system for selecting one or another option may be implicitly overruled; thus creating an implicit and non-conscious ‘change of mind’. Finally, the question is raised: in what way do such rapid implicit ‘changes of mind’ help retain one’s self-control and free-will behavior?

Intraneuronal accumulation of the microtubule associated protein Tau is largely recognized as an important toxic factor linked to neuronal cell death in Alzheimer’s disease and tauopathies. While there has been progress uncovering mechanisms leading to the formation of toxic Tau tangles, less is known about how intraneuronal Tau levels are regulated in health and disease. Here, I will discuss our recent work showing that the intracellular trafficking adaptor protein Numb is critical to control intraneuronal Tau levels. Inactivation of Numb in retinal ganglion cells increases monomeric and oligomeric Tau levels and leads to axonal blebbing in optic nerves, followed by significant neuronal cell loss in old mice. Interestingly, overexpression of the long isoform of Numb (Numb-72) decreases intracellular Tau levels by promoting exocytosis of monomeric Tau. In TauP301S and triple transgenic AD mouse models, expression of Numb-72 in RGCs reduces the number of axonal blebs and prevents neurodegeneration. Finally, inactivation of Numb in TauP301S mice accelerates neurodegeneration in both the retina and spinal cord and leads to precocious paralysis. Taken together, these results uncover Numb as a essential regulator of Tau homeostasis in neurons and as a potential therapeutic agent for AD and tauopathies.

Traumatic injury in the nervous system leads to devastating consequences such as paralysis. The regenerative capacity of the nervous system is limited in adulthood. In this talk, Dr. Anindya would be sharing how the simple nematode C. elegans with its known connectome can inform us about the biology of nervous system repair.