Characterization of A11 Neurons Projecting to the Spinal Cord of Mice

Koblinger, Kathrin; Füzesi, Tamás; Ejdrygiewicz, Jillian; Krajacic, Aleksandra; Bains, Jaideep S.; Whelan, Patrick J.

doi:10.1371/journal.pone.0109636

Cited by 88 publications

(83 citation statements)

References 59 publications

(63 reference statements)

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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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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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“…Dopaminergic posterior tuberculum/A11: In both fish and mammals these nuclei contain the only dopaminergic cell type that projects to the spinal cord (Tay et al, 2011; Koblinger et al, 2014), and are specified by the expression of common transcription factors (Löhr et al, 2009). …”

Section: Methodsmentioning

confidence: 99%

Ancestral Circuits for the Coordinated Modulation of Brain State

Lovett-Barron¹,

Andalman²,

Allen³

et al. 2017

Cell

148

144

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SUMMARY Internal states of the brain profoundly influence behavior. Fluctuating states such as alertness can be governed by neuromodulation, but the underlying mechanisms and cell types involved are not fully understood. We developed a method to globally screen for cell types involved in behavior by integrating brain-wide activity imaging with high-content molecular phenotyping and volume registration at cellular resolution. We used this method (MultiMAP) to record from 22 neuromodulatory cell types in behaving zebrafish during a reaction-time task that reports alertness. We identified multiple monoaminergic, cholinergic, and peptidergic cell types linked to alertness and found that activity in these cell types was mutually correlated during heightened alertness. We next recorded from and controlled homologous neuromodulatory cells in mice; alertness-related cell-type dynamics exhibited striking evolutionary conservation and modulated behavior similarly. These experiments establish a method for unbiased discovery of cellular elements underlying behavior and reveal an evolutionarily conserved set of diverse neuromodulatory systems that collectively govern internal state.

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“…Note that a large number of intensely GAD-IR processes were observed in the hypothalamus (ventral) region including A11, and more weakly GAD-IR processes were present in the thalamus (dorsal). The delimited areas in a-c are shown at higher magnification in d- ◂ [2,4,5,33]. In these previous studies, it was also reported that there were projections to the spinal cord derived from both non-TH and TH neurons of the A11 region.…”

Section: Projection To the Spinal Cordmentioning

confidence: 77%

“…Dopaminergic neurons are enriched in several brain regions designated as A8-A16 [1]. Among these, the A11 dopaminergic system is the only dopaminergic system that gives rise to descending projections to the spinal cord [2,4,5]. In addition to these particular neural connections, the fact that dopaminergic receptors are present in the spinal cord, and that dopamine receptor agonists alleviate the symptoms of restless legs syndrome (RLS), led to the hypothesis that hypo-activity of A11 neurons is a contributing factor in the pathogenesis of RLS [3].…”

Section: Introductionmentioning

confidence: 99%

Three Types of A11 Neurons Project to the Rat Spinal Cord

et al. 2017

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The A11 dopaminergic cell group is the only group among the A8-A16 dopaminergic cell groups that includes neurons innervating the spinal cord, and a decrease in dopaminergic transmission at the spinal cord is thought to contribute to the pathogenesis of restless legs syndrome. However, the mechanisms regulating the neuronal activity of A11 dopaminergic neurons remain to be elucidated. Unraveling the neuronal composition, distribution and connectivity of A11 neurons would provide insights into the mechanisms regulating the spinal dopaminergic system. To address this, we performed immunohistochemistry for calcium-binding proteins such as calbindin (Calb) and parvalbumin (PV), in combination with the retrograde tracer Fluorogold (FG) injected into the spinal cord. Immunohistochemistry for Calb, PV, or tyrosine hydroxylase (TH), a marker for dopaminergic neurons, revealed that there were at least three types of neurons in the A11 region: neurons expressing Calb, TH, or both TH and Calb, whereas there were no PV-immunoreactive (IR) cell bodies. Both Calb- and PV-IR processes were found throughout the entire A11 region, extending in varied directions depending on the level relative to bregma. We found retrogradely labeled FG-positive neurons expressing TH, Calb, or both TH and Calb, as well as FG-positive neurons lacking both TH and Calb. These findings indicate that the A11 region is composed of a variety of neurons that are distinct in their neurochemical properties, and suggest that the diencephalospinal dopamine system may be regulated at the A11region by both Calb-IR and PV-IR processes, and at the terminal region of the spinal cord by Calb-IR processes derived from the A11 region.

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Characterization of A11 Neurons Projecting to the Spinal Cord of Mice

Cited by 88 publications

References 59 publications

A descending dopamine pathway conserved from basal vertebrates to mammals

A descending dopamine pathway conserved from basal vertebrates to mammals

Ancestral Circuits for the Coordinated Modulation of Brain State

Three Types of A11 Neurons Project to the Rat Spinal Cord

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