Principles governing the operation of synaptic inhibition in dendrites

Abstract:

In the neocortex and hippocampus about 20% of the neurons are inhibitory; their axons ramify locally and contact particular dendritic subdomains of their target neuron, where each axon often makes 10-20 synapses. The functional implications of such connectivity design are not understood. Our �dendro-centric� theoretical study highlights three new principles for inhibition in branched dendrites, (i) With multiple synaptic contacts, inhibition operates globally, spreading hundreds of micrometers away from the inhibitory synapses; (ii) Inhibition in regions lacking inhibitory synapses may exceed that at the synaptic sites themselves; (iii) Distal inhibition effectively dampens more proximal excitable dendritic �hotspots�, thus powerfully controlling the neuron�s output. We introduce the notion of �coverage� for dendritic inhibition and suggest a major reevaluation in our understanding of synaptic inhibition in neurons.