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要旨:
The prefrontal cortico-midbrain pathway is thought to play an important role in the regulation of the firing pattern in the ventral tegmental area (VTA) neurons. The understanding of the mechanisms that underlie the regulation of the midbrain dopamine neurons is critical to elucidate the reward system as well as certain pathological conditions such as drug addiction or schizophrenia. Descending prefrontal cortex (PFC) projections to the VTA have been primarily documented in the rodent brain (Maurice et al., 1999; Sesack and Carr, 2002). Furthermore, several anatomical studies based on the use of anterograde tracers in the nonhuman primate, have shown labeled fibers in the VTA that originated in the medial frontal cortex and anterior cingulate cortex (areas 25, 32 and 24), orbitofrontal cortex (areas 11 and 14) and dorsolateral prefrontal cortex (area 9 and 46) (Chiba et al., 2001; Frankle et al., 2006).
In order to complete the study of the direct inputs from the PFC to the VTA, the retrograde tracer 3 Fast Blue (FB) was placed in the mesencephalic ventral and dorsal tegmentum in Macaca fascicularis monkey, including the ventral tegmental area. We analyzed three cases injected with FB through a Hamilton syringe in the ventral mesencephalon. A magnetic resonance (MR) examination to localize the stereotaxic coordinates of the injection site was performed in all the animals used in this study. After 2 weeks survival, animals were deeply anesthetized and perfused through the heart with 4 paraformaldehyde. Several additional cases with 3H-aminoacid injections reported previously (Insausti and Amaral, 2008) were also available for analysis under dark field illumination.
Our preliminary results showed labeled neurons in the deep layers of principally, the medial frontal and orbitofrontal cortices, including areas 24, 32 and 25, and the orbitofrontal cortex (areas 11, 13, 12 and 14). Comparatively, the dorsolateral prefrontal (area 10, 9, 46 and 6) cortex displayed far fewer labeled neurons. Most of the labeled neurons were situated at the level of the medial part of caudal area 9 and rostral area 6.
The anterograde tracer experiments (5 cases with 3H-aminoacid deposits placed in the orbitofrontal cortex, and 3 cases in the medial frontal cortex) confirmed the existence of these projections, thus ruling out the contamination by fibers of passage at the retrograde tracer injection sites.
Our data suggest that the influence of medial frontal and orbitofrontal cortices on the dopaminergic ascending projections is much higher than from the dorsolateral prefrontal cortex.
