Ventral tegmental (A10) system: neurobiology. 1. anatomy and connectivity

Abstract

Introduction: The VTA contains the A 10 group of dopamine (DA) containing neurons. These neurons have ben grouped into nuclei to be found on the floor of the midbrain tegmentum - the Nucleus paranigralis (Npn), Nucleus interfasicularis (Nif), Nucleus parabrachialis (Npbp) and the Nucleus linearis (rostralis and caudalis) *. The VTA is traversed by many blood vessels and nerve fibers **. Close to its poorly defined borders are found DA (A8, A9, A11) and 5-HT containing neurons (B8). * Figures 2-4 show electron micrographs and drawings ** Figure 6 , electronmicrographs show neurovascular contacts in the rat and cat that could be used for, say, steroid hormone influence on neurotransmission. Efferent projections of the VTA can be divided into 5 subsystems. The mesorhombencephalic projects to other monoaminergic nucei, the cerebellum and a fine projection descends to other tegmental nuclei as far as the inferior olive. Fibers to the spinal cord havenot been demonstrated. The mesodiencephalic path projects to several thalamic and hypothalamic nuclei andpossibly the median eminence. Functionally important examples are the anterior hypothalamic-preoptic area, Nucleus medialis dorsalis and reuniens thalami. These two subsystems are largely non-dopaminergic. A minor mesostriatal projection is overshadowed by the large mesolimbic projection to the Nucleus accumbens, Tuberculum olfactorium, Septum lateralis and Nucleus interstitialis stria terminalis. There are also mesolimbic connections with several amygdaloid nuclei (especially centralis and basolateralis), the olfactory nuclei and Entorhinal cortex. A minor projection to the hippocampus has been detected. The mesocortical pathway projects to sensory (e.g. visual) motor, limbic (e.g. retrosplenial) and polysensory association coretices (e.g. prefrontal). Prefrontal, orbitofrontal (insular) and cingulate cortices receive the most marked innervation from the VTA. A more widespread presence of DA in other cortices of rodents becomes progressively more evident in carnivores and primates. Most but not all projections are unilateral (see Table VI for % crossed). Some neurons project to more than one area in mesodiencephalic, limbic and cortical systems. The majority of these fibers ascend in the medial forebrain bundle (MFB). Most areas receiving a projection from the VTA (DA or non-DA) project back to the VTA. The septo-hippocampal complex in particiular and the limbic system in general provide quantitatively much less feedback than other areas. The role of the VTA as a mediator of dialogue with the fronto - striatal and limbic / extrapyramidal system is discussed under the theme of " circuit " systems (Figure 11, 12 & 13). The large convergence of afferents to certain VTA projection areas (e.g., prefrontal, entorhinal cortices, lateral septum, central amygdala, habenula, and N. accumbens) is discussed under the theme of " convergence " systems (Figure 15 & 16). Animal studies clearly demonstrate that the VTA in general, and its DA projections in particular are strategically organized to influence integrative neural function in diverse regions of the meso-, di- and telencephalon.