Interactions between grafted serotonin neurons and adult host rat hippocampus

We have followed the development of physiological and functional properties of serotonin-containing raphe neurons grafted into an adult host hippocampus as a model system for graft-host interactions. These raphe cells have no clear identifying properties on the day of grafting: they develop them while growing in the host. Raphe neurons, recorded 1 month after grafting, possess adult normal physiological properties. These include high input resistance, slow membrane time constant, lack of inward rectification, a transient outward rectification, broad spikes having a Ca2+ component, lack of accommodation, and a large afterhyperpolarization. The graft is first innervated by host fibers and later projects to the host tissue. When stimulated, postsynaptic hyperpolarized responses are recorded in hippocampal neurons. In the freely moving rat, raphe grafts can restore sleep-wakefulness variations in an evoked population response of the hippocampus to afferent stimulation, which is eliminated by depletion of serotonin. These studies illustrate that grafted serotonin neurons develop functional relations with a host brain.