Understanding the relationship between behavior and underlying brain function constitutes one of the most complex intellectual challenges today. A central dilemma in functional neuroimaging of animal behaviors has been the fact that conventional neuroimaging protocols using positron emission tomography (PET), single photon emission computer tomography (SPECT) and functional magnetic resonance imaging (fMRI) generally rely on immobilization of the subject, which extinguishes all but the simplest activity and introduces the additional variables of restraint stress. The result is that brain function of core mammalian behaviors such as aggression, mating, foraging and social interaction - all requiring locomotion - remains poorly understood. The problem of behavioral restraint can be solved if a single-pass extraction radiotracer is administered by non-agitating means, and regional brain activation is imaged after completion of the behavioral task and capture of the tracer. We have previously designed an implantable, miniature, infusion pump (MIP) for the administration of radiotracers. We now propose to apply this technology to the administration of [64Cu]-PTSM, a novel single-pass extraction cerebral blood flow (CBF) tracer used for PET applications.
Specific aims are: 1) To compare in an animal model, the relative regional CBF tracer distribution of [64Cu]-PTSM to that of the classical perfusion tracer [14C]-iodoantipyrine by dual label autoradiography. 2) To validate using PET that [64Cu]-PTSM when administered by the MIP can be used for the assessment of functional brain activation in freely moving animals during performance of a standardized locomotor challenge. Here [64Cu]-PTSM is administered by the MIP pump during either treadmill walking or during a quiescent control condition. Regional brain activation is imaged using PET after completion of the behavioral task and capture of the tracer. Application of a portable infusion pump to the administration of [64Cu]-PTSM promises to allow use of PET to functional neuroimaging paradigms in freely-moving subjects - something that has previously not been feasible using conventional neuroimaging protocols. Future applications of these methods promise to increase our understanding of the basic building blocks of normal behavior. Such knowledge may provide the basis of an improved integration of a functional brain anatomy in the context of mental disorders.
| Holschneider, D P; Yang, J; Sadler, T R et al. (2008) Changes in regional brain perfusion during functional brain activation: comparison of [(64)Cu]-PTSM with [(14)C]-Iodoantipyrine. Brain Res 1234:32-43 |
