Three-dimensional computer reconstruction of midbrain dopaminergic neuronal populations: From mouse to man

German, Dwight C.; Schlusselberg, Daniel S.; Woodward, Donald J.

doi:10.1007/bf01248996

Cited by 107 publications

(46 citation statements)

References 15 publications

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“…8, 9; Table 5). We have used these techniques previously to examine the distribution of midbrain dopaminergic neurons in humans and rodents (German et al, 1983(German et al, ,1985. Cell-frequency maps indicate similarities and differences in the LC in the 5 brains examined.…”

Section: Lc Cellular Distributionmentioning

confidence: 99%

The human locus coeruleus: computer reconstruction of cellular distribution

et al. 1988

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Quantitative neuroanatomical techniques were developed to map the distribution of norepinephrine-containing locus coeruleus (LC) neurons in the adult human brain. These neurons reside in the dorsolateral pontine tegmentum and are identifiable by their neuromelanin pigment content. Five brains, ranging in age from 60 to 104 years, were examined. Outlines of coronal or sagittal sections containing the LC were entered into a computer along with the location of each cell, certain neuroanatomical landmarks, and cell size. Sections were aligned with specific neuroanatomical landmarks so that the computer-generated distribution of cells was representative of the in situ distribution of cells. Analysis of (1) the number of cells in sections throughout the rostrocaudal extent of the nucleus, (2) cell size, (3) 3-dimensional reconstructions of the distribution of cells within the brain stem, and (4) 2-dimensional cell-frequency maps, make it possible to quantitatively characterize the distribution of cells within this large nucleus. The total estimated number of LC cells on both sides of the brain ranged from 45,562 to 18,940 (youngest to oldest), and mean soma area ranged from 835 to 718 micron 2 (youngest to oldest). The nucleus is “tube-like” in shape, has a rostrocaudal extent of approximately 16 mm, and is bilaterally symmetrical. Two-dimensional cell-frequency maps were developed to illustrate the regional distribution of cell frequencies at any rostrocaudal/mediolateral point on the horizontal plane; the total unilateral area of the LC ranged from 32.8 to 17.2 mm2 (youngest to oldest). The techniques developed to characterize the 2- and 3-dimensional distributions of LC neurons can be used in future studies to quantitatively examine the effects of aging and disease on this and other brain nuclei.

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Section: Lc Cellular Distributionmentioning

confidence: 99%

The human locus coeruleus: computer reconstruction of cellular distribution

et al. 1988

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“…In mammals, most DA-containing neurons clustered within three major mesencephalic groups: A8 cells in the retrorubral field, A9 cells in the substantia nigra (SN) and A10 cells in the ventral tegmental area (VTA) (Dahlstrom & Fuxe, 1964;Ungerstedt, 1971;Lindvall & Bjorklund, 1974;Fallon & Moore, 1978;German et al, 1983;Arsenault et al, 1988;German & Manaje, 1993). Similar organizations of DA cell bodies have been demonstrated in reptiles (Smeets et al, 1987;Smeets, 1988;Gonzalez et al, 1994) and birds 4 (Smits et al, 1990;Durstewitz et al, 1999).…”

Section: Functional Anatomy Of the Mesencephalic Da Projectionsmentioning

confidence: 99%

Behavioral functions of the mesolimbic dopaminergic system: An affective neuroethological perspective

Alcaro

Huber

Panksepp

2007

Brain Research Reviews

526

294

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The mesolimbic dopaminergic (ML-DA) system has been recognized for its central role in motivated behaviors, various types of reward, and, more recently, in cognitive processes. Functional theories have emphasized DA's involvement in the orchestration of goal-directed behaviors, and in the promotion and reinforcement of learning. The affective neuroethological perspective presented here, views the ML-DA system in terms of its ability to activate an instinctual emotional appetitive state (SEEKING) evolved to induce organisms to search for all varieties of life-supporting stimuli and to avoid harms.A description of the anatomical framework in which the ML system is embedded is followed by the argument that the SEEKING disposition emerges through functional integration of ventral basal ganglia (BG) into thalamocortical activities. Filtering cortical and limbic input that spread into BG, DA transmission promotes the "release" of neural activity patterns that induce active SEEKING behaviors when expressed at the motor level. Reverberation of these patterns constitutes a neurodynamic process for the inclusion of cognitive and perceptual representations within the extended networks of the SEEKING urge. In this way, the SEEKING disposition influences attention, incentive salience, associative learning, and anticipatory predictions.In our view, the rewarding properties of drugs of abuse are, in part, caused by the activation of the SEEKING disposition, ranging from appetitive drive to persistent craving depending on the intensity of the affect. The implications of such a view for understanding addiction are considered, with particular emphasis on factors predisposing individuals to develop compulsive drug seeking behaviors.

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“…T he dopamine neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) comprise about two-thirds of the dopaminergic neurons in the CNS (1,2). These midbrain dopamine neurons send dense projections to forebrain structures, including the caudate putamen (CPu), nucleus accumbens (NAc), and olfactory tubercle, as well as sparser projections to the prefrontal cortex, amygdala, and hippocampus (2).…”

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confidence: 99%

Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia

Hnasko¹,

Perez²,

Scouras³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

194

211

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A line of dopamine-deficient (DD) mice was generated to allow selective restoration of normal dopamine signaling to specific brain regions. These DD floxed stop (DDfs) mice have a nonfunctional Tyrosine hydroxylase (Th) gene because of insertion of a Neo R gene flanked by lox P sites targeted to the first intron of the Th gene. DDfs mice have trace brain dopamine content, severe hypoactivity, and aphagia, and they die without intervention. However, they can be maintained by daily treatment with L-3,4-dihydroxyphenylalanine (L-dopa). Injection of a canine adenovirus (CAV-2) engineered to express Cre recombinase into the central caudate putamen restores normal Th gene expression to the midbrain dopamine neurons that project there because CAV-2 efficiently transduces axon terminals and is retrogradely transported to neuronal cell bodies. Bilateral injection of Cre recombinase into the central caudate putamen restores feeding and normalizes locomotion in DDfs mice. Analysis of feeding behavior by using lickometer cages revealed that virally rescued DDfs mice are hyperphagic and have modified meal structures compared with control mice. The virally rescued DDfs mice are also hyperactive at night, have reduced motor coordination, and are thigmotactic compared with controls. These results highlight the critical role for dopamine signaling in the dorsal striatum for most dopamine-dependent behaviors but suggest that dopamine signaling in other brain regions is important to fine-tune these behaviors. This approach offers numerous advantages compared with previous models aimed at examining dopamine signaling in discrete dopaminergic circuits.canine adenovirus ͉ feeding behavior ͉ locomotor behavior ͉ viral gene transfer ͉ tyrosine hydroxylase T he dopamine neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) comprise about two-thirds of the dopaminergic neurons in the CNS (1, 2). These midbrain dopamine neurons send dense projections to forebrain structures, including the caudate putamen (CPu), nucleus accumbens (NAc), and olfactory tubercle, as well as sparser projections to the prefrontal cortex, amygdala, and hippocampus (2). These dopaminergic circuits have been implicated in a variety of fundamental mammalian behaviors such as movement, feeding, reward responses, and learning (for review, see refs. 3-6).Dopamine-deficient (DD) mice (7) have been a useful genetic model to study the role of dopamine in these behaviors. DD mice are indistinguishable from littermates until Ϸ10 days, when they begin to manifest reduced body weight (BW) compared with controls, and, without intervention, DD mice will starve at Ϸ3 weeks (7). However, daily L-3,4-dihydroxyphenylalanine (Ldopa) treatment restores dopamine to the brain and induces Ϸ8 h of hyperactivity during which the DD mice consume enough food to survive (7,8). This ability to temporarily restore dopamine signaling with L-dopa is the primary advantage of the DD mouse model compared with the 6-hydroxydopamine-lesion model because it allows us to...

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Three-dimensional computer reconstruction of midbrain dopaminergic neuronal populations: From mouse to man

Cited by 107 publications

References 15 publications

The human locus coeruleus: computer reconstruction of cellular distribution

The human locus coeruleus: computer reconstruction of cellular distribution

Behavioral functions of the mesolimbic dopaminergic system: An affective neuroethological perspective

Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia

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