Final Report Summary - CHANNELRHODOPSIN (Information processing in distal dendrites of neocortical layer 5 pyramidal neurons) Nerve cells have elaborate dendritic trees emanating from the cell body. A single neuron in the central nervous system receives thousands of synapses positioned at sites throughout the neuron's dendritic tree. These inputs are integrated to form a neuronal output, the action potential that is generated at the axon initial segment. Neurotransmitter release from presynaptic axons activates synapses generating an electrical signal, a postsynaptic potential. In the neocortex direct electrical recordings from distal dendrites have confirmed prediction from the cable theory demonstrating a dramatic distance-dependent attenuation of postsynaptic potentials from their dendritic site of generation to the soma. However, dendritic spiking mediated by Ca2+-channel or N-methyl-D-aspartate (NMDA) receptor activation is capable to propagate to the soma and to elicit action potentials. How synapses generated at more distal sites in the dendritic tree influence the action potential output of the postsynaptic neuron and how the propagation of dendritic spikes can be regulated remain unresolved questions in single neuron computation. Recently, it has been shown that NMDA receptor activation in distal tuft and in basal dendrites emerges as the prevailing mechanism of how distal synapses raise their voices potentially enabling forward propagation to the soma and finally leading to neuronal output. Inhibitory interneurons in the brain can be subdivided into different classes according to their target-region on excitatory pyramidal neurons. Dendrite-targeting interneurons could potentially inhibit forward-propagation of dendritic spikes. Indeed, indirect evidence suggested a role of neocortical deep layer interneurons in controlling dendritic excitability. We have addressed the question whether and how superficial dendrite-targeting interneurons modulate dendritic spiking. We have first characterised inhibitory interneurons in the vicinity of neocortical layer 5 apical tuft dendrites. Using paired electrical recordings from identified interneurons and pyramidal neuron dendrites we show for the first time that a specific class of inhibitory interneurons in the superficial layers of the neocortex can suppress dendritic spiking in layer five pyramidal neurons. These results demonstrate the impact of a single superficial inhibitory interneuron on information processing in a single pyramidal neuron by acting as a veto neuron inhibiting dendritic spiking and neuronal output.