The aim of the current proposal is to investigate how synaptic inputs that innervate the distal dendrites of central neurons are integrated to form a neuronal output. The distal dendritic tree is the dendritic compartment furthest away from the action potential initiation zone. In the neocortex ascending afferent and intra-cortical information converges in neocortical layer 1 suggesting a prominent functional role, however only the most distal apical dendrites of layer 5 pyramidal neurons enter layer 1. We hypothesise that synaptic inputs are locally integrated at distal dendritic sites, perhaps in individual dendritic branches, leading to the generation of dendritic spikes as an output of compartmentalised integration. This hypothesis has until now been difficult to test experimentally as such distal dendrites are not amenable to direct electrical recording techniques. We plan to explore if these structures are capable of generating regenerative spike activity by remotely exciting individual branches of the distal apical dendritic tree using light-activated ion channels expressed in neocortical pyramidal neurons and measuring electrical activity at accessible nearby large calibre apical dendritic trunk sites and the soma. The use of light-activated channels to excite neurons is at the cutting edge of neuroscience research. Our plan is to use these channels to excite individual dendritic elements; a proposal that will require a multidisciplinary approach utilizing molecular, microscopy and electrophysiological approaches in an attempt to unravel the integrative operations of central neurons.
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