Ventral mesencephalon

Several classes of drugs modulate the firing rates or patterns of midbrain dopamine neurons by direct, monosynaptic, or indirect, polysynaptic, inputs to the cell bodies within the ventral mesencephalon (i.e., nicotine and opiates). In contrast, amphetamine, cocaine, and methylphenidate act at the level of the dopamine terminal interfering with normal processes of transmitter packaging, release, reuptake, and metabolism. 

Spenger C, Hyman C, Studer L, Egli M, Evtouchenko L, Jackson C, Dahl-Jorgensen A, Lindsay RM, Seiler RW (1995) Effects of BDNF on dopaminergic, serotonergic, and GABAergic neurons in cultures of human fetal ventral mesencephalon. Exp Neurol 133 50-63... 

Armstrong, R.J., Tyers, P., Jain, M, Richards, A., Dunnett, S.B., Rosser, A.E., Barker, R.A. (2003). Transplantation of expanded neural precursor cells from the developing pig ventral mesencephalon in a rat model of Parkinson s disease. Exp Brain Res, 151, 204-17. 

Seroogy KB, Ceccatelli S, Schalling M, Hokfelt T, Frey P, Walsh J, Dockray G, Brown J, Buchan A, Goldstein M (1989) A subpopulation of dopaminergic neurons in the rat ventral mesencephalon contains both neurotensin and cholecystokinin. Brain Res 55 88-98. 

Seroogy KB, Mehta A, Fallon JH (1987) Neurotensin and cholecystokinin coexistence within neurons of the ventral mesencephalon projections to forebrain. Exp Brain Res 68 271-289. 

More recent studies in monkeys by Schultz and colleagues have totally reversed this view (Ljungberg et al., 1991, 1992 Mirenowicz and Schultz, 1994, 1996). When monkeys are not first overtrained in the task, then the dopamine cells recorded in the ventral mesencephalon respond to various aspects of the task. Exactly when the dopamine cells fire a burst of action potentials depends on the state of training in the task (Ljungberg et al., 1992). While the monkeys are naive to the situation the cells respond about 200 ms after the delivery of a reward (Mirenowicz and Schultz, 1994). As the behavior is acquired, this burst of dopamine release is timed to follow stimuli that have come to predict the arrival of the reward, even if the trigger is a movement of the animal itself and not an explicit external cue. As the task is learned, the dopamine burst moves to earlier and earlier predictors of reward (Schultz et al., 1993). Importantly, if a reward is omitted in some trials, the dopamine cells are silenced at the point where an expected reward is not delivered (Mirenowicz and Schultz, 1996). These results appear remarkably consistent with the modern learning theory concepts of reward (Schultz et al., 1993, 1997 Schultz, 1997, 2000 Waelti et al., 2001). 

Dumas S, Horellou P, Helin C, Mallet J (1992) Co-expression of tyrosine hydroxylase messenger RNA 1 and 2 in human ventral mesencephalon revealed by digoxigenin- and biotin-labelled oligodeoxyribonucleotides. J Chem Neuroanat 5 11—18. 

Gates, M. A., Laywell, E. O., Fillmore, H., and Steindler, O. A., Astrocytes and extracellular matrix following intracerebral transplantation of embryonic ventral mesencephalon or lateral ganglionic eminence, Neuroscience, 74, 579, 1996. 

The number of commercially available NS/PC lines has been constantly increasing. The NSC lines ReNcell VM and ReNcell CX (Millipore) are derived from developing human brains, ReNcell VM from the ventral mesencephalon (VM) and ReNcell CX cells from the cortical (CX) regions of the brain. For immortalization, they were transduced with the myc transcription factor. ReNcell lines grow as adherent cultures and have the ability to differentiate into neurons and glia cells. Also hESC (EI9/derived... 

Bischoff S, Barhanin J, Bettler B, Mulle C, Heinemann S (1997) Spatial distribution of kainate receptor subunit mRNA in the mouse basal ganglia and ventral mesencephalon. J Comp Neurol 579 541-562. 

Northern blots and in situ hybridization data showed that BDNF mRNA is mainly present in the brain and suggested a putative trophic effect for neurotrophins not only on PNS neurons but also on intrinsic neurons of the central nervous system (CNS). In fact, both NGF and BDNF were found to support central cholinergic neurons in culture (Martinez et al., 1985 Hefti, 1986 Hartikka and Hefti, 1988 Hatanaka et al., 1988 Alderson et al., 1990 Knusel et al., 1991). However, only BDNF supported chick and rat retinal ganglion cells, dopaminergic neurons of the ventral mesencephalon, and GABAergic neurons of the basal forebrain and striatum (Lindsay et al., 1985 Alderson et al., 1990 Hyman et al., 1991, 1994 Knusel et al., 1991, 1994 Ventimiglia et al., 1995). 

Another system in the brain, the basal ganglia, has also been subject of particularly intense research. BDNF, NT-3 and NT-4/5, but not NGF, have shown clear effects on differentiation of both dopaminergic and GABAergic neurons of the ventral mesencephalon. Moreover, NT-3 has also been shown to promote the survival of both populations of neurons (Hyman et al., 1994, Studer et al., 1995). In addition, the presence of trkB and trkC receptors in the striatum, together with the existence of receptor-mediated retrograde transport of BDNF and NT-3 from the striatum to the substantia nigra in adult rat brain (Wiegand et al.,... 

NT-4/5 has survival and/or differentiation effects on a wide range of brain neurons. Survival effects have been shown on embryonic cholinergic neurons of the basal forebrain, noradrenergic neurons of the locus coeruleus (Friedman et al., 1993), and dopaminergic mesencephalic neurons (Hynes et al., 1994). In addition, NT-4/5 was also shown to promote differentiation effects on GABAergic cells of the ventral mesencephalon (Hyman et al.,... 

Saporta, S., Borlongan, C., Moore, J., Mejia-Millan, E., Jones, S. L., Bonness, P., Randall, T. S., Allen, R. C., Freeman, T. B., and Sanberg, P. R. (1997), Microcarrier enhanced survival of human and rat fetal ventral mesencephalon cells implanted in the rat striatum. Cell Transplant 6(6) 579-.584. 

Fig. 13. Diagrammatic representation of the efferent connections of the ventral mesencephalon. C-P, nucleus caudatus-putamen Ac, nucleus accumbens Am, amygdala VM, ventromedial nucleus of thalamus HL, lateral habenular nucleus SNc, substantia nigra (pars compacta) SNr, substantia nigra (pars reticulata) AVT, ventral tegmental area of Tsai SC, superior colliculus NRa dorsal raph nucleus LC, locus coeruleus TPC, pedunculo pontine nucleus. (From Beckstead et al., 1979, with kind permission of the authors.)...

Fig. 17. Representative autoradiographs of the ventral mesencephalon. The relative rates of glucose utilization are related directly to relative optical densities. (A) Conscious, saline treated. The pars compacta can be identified as a well-defined line of relatively increased optical density. (B) Conscious, apomorphine treated. The pars compacta and pars reticulata each display marked increases in relative optical density. (C) Chloral hydrate anesthesia, saline treated. Glucose use in the pars compacta is minimally reduced by anesthesia and remains a well-defined band of optical density. (D) Chloral hydrate anesthesia, apomorphine treated. Glucose use in the pars compacta is reduced, and optical density in the pars compacta is no longer different from that in the adjacent pars reticulata. (From Grome and McCulloch 1981a).

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