Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus
In the present study the microdialysis technique has been used as a tool for the study of functional regulation of intracerebrally grafted cholinergic and monoaminergic neurons as well as for the analysis of graft-host interactions. Fetal noradrenergic, serotonergic, dopaminergic, and cholinergic neurons were transplanted into the hippocampus or striatum previously denervated of their intrinsic monoaminergic or cholinergic afferents. After a few months survival, when the grafts had reinnervated the surrounding target, dialysis probes were implanted into the graft-reinnervated region. Although the graft-derived fiber and terminal density varied substantially from one animal to another the transmitters in the extracellular space were maintained at near-normal levels, not only under baseline conditions, but also during K(+)-induced depolarization, transmitter-selective uptake blockade, and tetrodotoxin. This suggests that the grafted neurons possess efficient autoregulatory properties despite their ectopic location. The results also show that monoamine release in the graft-reinnervated host target is impulse-dependent, and that the neurons are spontaneously functionally active at the synaptic level. Electrical stimulation of the lateral habenula (which has previously been identified as a powerful activator of the intrinsic hippocampal cholinergic and noradrenergic afferents) produced a similar increase in the release of these transmitters in the intact and grafted hippocampi. A complex environmental stimulus, such as handling, induced a consistent increase in acetylcholine but not noradrenaline release in the hippocampus. These findings suggest that grafted cholinergic and noradrenergic neurons can be functionally activated by host brain inputs.