IN-VIVO IMAGING OF NEUROMODULATORY SYNAPTIC TRANSMISSION USING PET - A REVIEW OF RELEVANT NEUROPHYSIOLOGY

Recent data from positron emission tomography (PET) imaging studies su ggest the possibility of studying synaptic transmission in vivo in hum ans. The approach will require a synthesis of two established techniqu es: brain activation studies (conventionally performed by measuring re gional cerebral blood flow or metabolism) and neurotransmitter recepto r imaging (using radiolabelled ligands that bind to specific neurorece ptors). By comparing neuroreceptor binding in subjects at rest and whi le performing an activation task, it may be possible to determine whet her a particular neurotransmitter is involved in performance of the ta sk. The underlying principle is that endogenous neurotransmitter compe tes with the injected radioligand for the same receptors, thereby inhi biting ligand binding. This effect will be even more pronounced during activation, as the synaptic concentration of transmitter rises. Thus, activation of a specific neurotransmitter will be detected as a decre ase in specific binding of the radioligand. In this paper we review ne urophysiological and biochemical literature to estimate the endogenous neurotransmitter concentration changes that will be expected to occur during an activation task, using the dopamine system as an example. W e calculate that the average synaptic dopamine concentration is approx imate to 100 nM and that it approximately doubles during activation. T his, along with consideration of the concentration of radioligand and affinities of the ligand and dopamine for dopamine receptors, suggests that physiological activation of a specific neurotransmitter system i s likely to be detectable with PET. (C) 1995 Wiley-Liss, Inc.