Intracerebral microdialysis as a tool to monitor transmitter release from grafted cholinergic and monoaminergic neurons.
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.
Kalén
P
P
Department of Medical Cell Research, University of Lund, Sweden.
Nilsson
O G
OG
Cenci
M A
MA
Rosengren
E
E
Lindvall
O
O
Björklund
A
A
D000818:Animals; D001923:Brain Chemistry; D016380:Brain Tissue Transplantation; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D003956:Dialysis; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000737:chemistry / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D018377:Neurotransmitter Agents; D013779:Tetrodotoxin; D011189:Potassium Chloride; D002394:Catechol O-Methyltransferase; D002802:Cholinesterases