Organization of diencephalic dopamine neurones projecting to the spinal cord in the rat

Skagerberg, Gunnar; Lindvall, Olle

doi:10.1016/0006-8993(85)91134-5

Cited by 201 publications

(119 citation statements)

References 37 publications

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“…LC, locus coeruleus. borszky, 1982;Skagerberg and Lindvall, 1985). Thus, DAT is likely to act at these terminal fields to regulate dopaminergic neurotransmission in accordance with the observation of highaffinity dopamine uptake in the hypothalamus (George and VanLoon, 1982).…”

Section: Discussionmentioning

confidence: 56%

Cell-type-specific expression of catecholamine transporters in the rat brain

1994

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The dopamine transporter (DAT) and norepinephrine transporter (NET) terminate catecholaminergic neurotransmission at synapses by high- affinity sodium-dependent reuptake into presynaptic terminals, and are the initial sites of action for drugs of abuse and antidepressants. In the present study, we used in situ hybridization combined with immunohistochemistry to study the distribution of DAT and NET mRNA in the adult rat brain. Cells were first immunolabeled with antisera directed against one of the catecholamine-synthetic enzymes, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), or phenylethanolamine-N-methyltransferase (PNMT), in order to identify dopaminergic, noradrenergic, or epinephrine-containing cells. The immunolabeled cells were subsequently assayed for their ability to express catecholamine transporter mRNAs by in situ hybridization using either a rat DAT or NET cRNA probe. All dopaminergic cell groups of the mesencephalon contained high levels of DAT mRNA but only the A12 and A13 dopaminergic cell groups of the diencephalon appear to express detectable levels of DAT. All norepinephrine-containing cell bodies in the brainstem (locus coeruleus and lateral tegmentum) appear to express NET mRNA. In contrast, epinephrine-containing cell bodies of the brainstem do not appear to express NET mRNA, which raises the possibility that epinephrine may utilize a transporter that is distinct from the other bioactive amines, or may act as an endocrine regulator that does not require rapid reuptake mechanisms. Moreover, the cell- type-specific expression of catecholamine transporters suggests that DAT and NET gene expression may be closely linked to cellular mechanisms that specify transmitter phenotype. The termination of neurotransmission is a critical component of neural signaling and depends on the rapid removal of neurotransmitters from the synaptic cleft. Pharmacological evidence indicates that the action of monoamines at the synapse is terminated predominantly by rapid reuptake into presynaptic nerve endings via neurotransmitter-specific, high-affinity, Na(+)-dependent membrane transporter proteins. The cDNAs encoding distinct transporter proteins for the monoamines dopamine, norepinephrine, and serotonin have been cloned, expressed, and characterized in a variety of heterologous systems (Blakely et al., 1991; Giros et al., 1991; Hoffman et al., 1991; Kilty et al., 1991; Pacholczyk et al., 1991; Shimada et al., 1991; Usdin et al., 1991). Although the monoamine transporters share a high degree of sequence homology, they are distinguished by their monoamine substrate specificities and by their differential sensitivities to a wide spectrum of transport antagonists. For example, pharmacological agents that potently inhibit norepinephrine and serotonin transport, such as desmethylimipramine and citalopram, have little effect on the activity of the dopamine transporter (Javitch et al., 1983).(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionmentioning

confidence: 56%

Cell-type-specific expression of catecholamine transporters in the rat brain

1994

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“…Another group of DA neurons, located in the hypothalamus (A11), sends descending projections to the spinal cord in lamprey (41), zebrafish (42), mice (43), rats (44), and primates (45) (Fig. S3B)] was transiently evoked following PT activation.…”

Section: Discussionmentioning

confidence: 99%

A descending dopamine pathway conserved from basal vertebrates to mammals

Ryczko

Cone

Alpert

et al. 2016

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

104

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Dopamine neurons are classically known to modulate locomotion indirectly through ascending projections to the basal ganglia that project down to brainstem locomotor networks. Their loss in Parkinson's disease is devastating. In lampreys, we recently showed that brainstem networks also receive direct descending dopaminergic inputs that potentiate locomotor output. Here, we provide evidence that this descending dopaminergic pathway is conserved to higher vertebrates, including mammals. In salamanders, dopamine neurons projecting to the striatum or brainstem locomotor networks were partly intermingled. Stimulation of the dopaminergic region evoked dopamine release in brainstem locomotor networks and concurrent reticulospinal activity. In rats, some dopamine neurons projecting to the striatum also innervated the pedunculopontine nucleus, a known locomotor center, and stimulation of the dopaminergic region evoked pedunculopontine dopamine release in vivo. Finally, we found dopaminergic fibers in the human pedunculopontine nucleus. The conservation of a descending dopaminergic pathway across vertebrates warrants re-evaluating dopamine's role in locomotion.D opaminergic neurons represent a vital neuromodulatory component essential for vertebrate motor control, and their loss in neurodegenerative disease is devastating. The meso-diencephalic dopamine (DA) neurons are known to provide ascending projections to the basal ganglia, which, in turn, provide input to cortical structure in mammals but also project caudally to the mesencephalic locomotor region (MLR), a highly conserved structure that controls locomotion in all vertebrates investigated to date (1-7; for review, see ref. 8). A growing body of evidence supports the view that basal ganglia connectivity is highly conserved among vertebrates, from lampreys to mammals (9-11; for review, see ref. 12), with some interspecies differences recently highlighted (13). As such, the homology between DA cell populations remains to be resolved in vertebrates. As a general rule, DA neurons from the meso-diencephalon send projections to the striatum in all vertebrates. In lampreys and teleosts, those neurons are located only in the diencephalon (posterior tuberculum), but in tetrapods and cartilaginous fishes (14) they are located in both the diencephalon and the mesencephalon. An increasing number of authors seem to agree with the hypothesis that at least some of the mesodiencephalic DA neurons located in the diencephalon are homologous in all vertebrates, and thus, homologous to at least a portion of the mammalian substantia nigra pars compacta (SNc)/ ventral tegmental area (VTA) (13, 15-19; for review, see ref. 20). Alternatively, it was suggested that the posterior tuberculum DA neurons projecting to the striatum in zebrafish are homologs of the mammalian DA neurons of the A11 group (21). This will be discussed below in light of the results of the present study.In lampreys, only a few meso-diencephalic DA neurons send ascending projections to the striatum (9, 22); the majority ...

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“…5,6 However, the existence of dopaminergic projections from the A11 cell group to the spinal cord as well as an intrinsic dopaminergic innervation within the spinal cord raises the possibility of an additional direct action of apomorphine at this level. 17,18 To investigate this statement, we directly delivered apomorphine at the spinal lumbosacral level with an intrathecal catheter, ie in the vicinity of the proerectile sacral parasympathetic nucleus. In preliminary experiments, we failed to modify the occurrence of ICP rises with i.t.…”

Section: Discussionmentioning

confidence: 99%

“…The physiological basis of the proerectile effects of apomorphine at the level of the sacral parasympathetic nucleus could be rep-resented by the activation of the hypothalamospinal dopaminergic pathway. 17 This dopaminergic pathway, possibly proerectile, deserves further investigation. Oxytocinergic and dopaminergic descending pathways may participate to the co-ordination of the somatic and autonomic component of the …”

Section: Discussionmentioning

confidence: 99%

Spinal proerectile effect of apomorphine in the anesthetized rat

et al. 2001

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Considering the presence of dopaminergic receptors in the lumbosacral spinal cord, we tested whether apomorphine could exert a proerectile effect by acting at the spinal level. Intracavernous (ICP) and blood pressures (BP) were measured in anesthetized rats. ICP rises were quanti®ed (duration, percentage of ICPmaximumameanBP (ICPmaxaBP 6 100), area under ICP curve (AUCaBP) and sum of AUCaBP after intravenous (i.v.) and intrathecal (i.t.) injections of apomorphine alone or in presence of i.t. oxytocin (10 ng). Both 10 and 30 m mg i.v. apomorphine dosings elicited erectile events evidenced by ICP rises. Upon the 30 m mg i.v. injection, duration of ICP rises were increased from 25 AE 10 to 69 AE 18 s (P`0.001), ICPmaxaBP 6 100 from 21 AE 3 to 50 AE 14% (P 0.001), AUCaBP from 3 AE 1 to 14 AE 6 s (P 0.002) and sum of AUCaBP from 5 AE 7 to 34 AE 35 s (P 0.021). Upon 30 m mg i.t. injections of apomorphine at the lumbosacral level, the number of ICP rises was increased from 0.2 AE 0.4 to 3.0 AE 1.5, ICPmaxaBP 6 100 from 16 AE 9 to 43 AE 12 and sum of AUCaBP from 1 AE 3 to 31 AE 15 s compared to vehicle injection (P`0.05 for all parameters). Injection of 30 m mg i.v. or i.t. apomorphine non-signi®cantly enhanced the number and amplitude of the ICP rises induced by 10 ng i.t. oxytocin. However, the enhancement of the amplitude of the ICP rises elicited by i.t. oxytocin was more pronounced with i.t. apomorphine than with i.v. apomorphine. These results suggest the existence of a spinal site of action for apomorphine which may (1) participate to generation of erection and (2) exerts a facilitator effect on erection of supraspinal origin.

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Organization of diencephalic dopamine neurones projecting to the spinal cord in the rat

Cited by 201 publications

References 37 publications

Cell-type-specific expression of catecholamine transporters in the rat brain

Cell-type-specific expression of catecholamine transporters in the rat brain

A descending dopamine pathway conserved from basal vertebrates to mammals

Spinal proerectile effect of apomorphine in the anesthetized rat

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