In vivo quantification of localized neuronal activation and inhibition in the rat brain using a dedicated high temporal-resolution beta +-sensitive microprobe

Abstract

Understanding brain disorders, the neural processes implicated in cognitive functions and their alterations in neurodegenerative pathologies, or testing new therapies for these diseases would benefit greatly from combined use of an increasing number of rodent models and neuroimaging methods specifically adapted to the rodent brain. Besides magnetic resonance (MR) imaging and functional MR, positron-emission tomography (PET) remains a unique methodology to study in vivo brain processes. However, current high spatial-resolution tomographs suffer from several technical limitations such as high cost, low sensitivity, and the need of restraining the animal during image acquisition. We have developed a beta(+)-sensitive high temporal-resolution system that overcomes these problems and allows the in vivo quantification of cerebral biochemical processes in rodents. This beta-MICROPROBE is an in situ technique involving the insertion of a fine probe into brain tissue in a way very similar to that used for microdialysis and cell electrode recordings. In this respect, it provides information on molecular interactions and pathways, which is complementary to that produced by these technologies as well as other modalities such as MR or fluorescence imaging. This study describes two experiments that provide a proof of concept to substantiate the potential of this technique and demonstrate the feasibility of quantifying brain activation or metabolic depression in individual living rats with 2-[(18)F]fluoro-2-deoxy-d-glucose and standard compartmental modeling techniques. Furthermore, it was possible to identify correctly the origin of variations in glucose consumption at the hexokinase level, which demonstrate the strength of the method and its adequacy for in vivo quantitative metabolic studies in small animals.

Fig 1.

Malonate effect on metabolic activity in the striatum of an anaesthetized rat. Five rats were injected with malonate (1 μl, 3 M) into the right striatum, and glucose consumption was measured 3 h later. The FDG uptake dramatically decreased in the injected striatum after malonate injection, whereas no detectable cell damage was noticed by using terminal deoxynucleotidyltransferase-mediated UTP end labeling reaction; however, autoradiographic analysis revealed a hypometabolism in the same order of magnitude as measured with the β-MICROPROBE. (Inset) Probe positioning and FDG autoradiography.

Fig 2.

Decay-corrected time-activity curve showing FDG uptake in rat 2 (Table 3) in rest condition and during vibrissal stimulation. This rat was stimulated unilaterally by continuously stroking the whiskers on the left side. The stimulation was initiated simultaneously with the injection of the second bolus dose of FDG. As shown on the autoradiographic image, the whisker-stroking markedly increased FDG uptake on the contralateral somatosensory cortex compared with the ipsilateral cortex. (Inset) Probe positioning and FDG autoradiography.