Mechanisms and plasticity of dendritic temporal sequence processing. (360G-Wellcome-092856_Z_10_A)

The mechanism by which neurons detect, organize and process numerous chemical and electrical signals is a fundamental problem in modern neuroscience. For example, the ability to discriminate spatiotemporal sequences of synaptic input has been suggested to be important for generating efficient coding schemes, and input sequence detection in general is a computation essential for animal behaviour. Previous work showed that dendrites could be responsive to the "direction" of temporally spaced inputs due to their cable filtering properties, suggesting that single neurons could act as basic sequence detectors. This "passive" direction selectivity was confirmed experimentally by Branco and colleagues, who also discovered that "active" NMDA receptor conductance recruitment dramatically enhances the direction sensitivity of somatic responses. In addition, Branco et al. 3 found that dendrites could discriminate not only directional sequences, bu1 also a wide range of spatiotemporal patterns. However, the role and impact of dendritic sequence processing is unknown for computation in different cortical areas and under different conditions. I plan to concentrate on two broad questions addressing how dendritic mechanisms can optimally discriminate sequences and potentially store selected input patterns. First, I will concentrate on the types of spatiotemporal patterns that can be distinguished from each other. Second, I will investigate whether specific input sequences can be stored, by probing plasticity processes triggered by different input patterns. Optimal conditions for dendritic pattern recognition. What is the optimal spatial distribution of inputs? What is the "optimal dendrite"? Interaction of patterns on the dendrite. The interaction of backpropagating action potential and patterned inputs. Influence of background noise. Sources of calcium ? pharmacology. Tthe effects of neuromodulation. Plasticity triggered.by patterned input. Plasticity induction readouts. Plasticity induction protocols - repetition of the same input pattern and pattern and action-potential combination Effect of neuromodulation in regulating of pattern-induced plasticity.