Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches

Waterman, Susanna A.

doi:10.1016/j.bbr.2007.11.004

Cited by 18 publications

(27 citation statements)

References 59 publications

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“…The locus coeruleus extends ventrolaterally into the sub coeruleus ventralis that contains about 600 cells. The locus coeruleus comprises mainly noradrenergic cells, but it overlaps with both serotonergic (more dorsally) and cholinergic (more ventrally) cell groups (Reiner et al, 2004b; Waterman and Harding, 2008; Puelles et al, 2007). In zebra finches the locus coeruleus has fewer cells than in non-oscines like quail (about 1300) or mammals like rats (about 3000), monkeys (about 7000) and humans (about 15000) (Barclay and Harding, 1988; Waterman and Harding, 2008; Berridge and Waterhouse, 2003).…”

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

“…One of the key differences between the noradrenergic system in mammals and songbirds is that the latter contains up to 10 times the norepinephrine level observed in homologous brain areas in mammals, resulting in a significantly higher ratio of norepinephrine to dopamine in birds (Barclay and Harding, 1988; Waterman and Harding, 2008). Norepinephrine levels have been measured in key brain areas associated with song.…”

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

“…The other is DBH, which is the enzyme required for the conversion of norepinephrine to dopamine and therefore is a marker for noradrenergic neurons. The locus coeruleus contains several DBH labeled cells as well as TH fibers (Mello et al, 1998; Bottjer, 1993; Appeltants et al, 2001; Waterman and Harding, 2008). Immunohistochemistry for DBH positive fibers delineates several song nuclei like HVC, RA, LMAN and Uva (Mello et al, 1998; Waterman and Harding, 2008).…”

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

“…The locus coeruleus contains several DBH labeled cells as well as TH fibers (Mello et al, 1998; Bottjer, 1993; Appeltants et al, 2001; Waterman and Harding, 2008). Immunohistochemistry for DBH positive fibers delineates several song nuclei like HVC, RA, LMAN and Uva (Mello et al, 1998; Waterman and Harding, 2008). Area X has very sparse albeit quantifiable DBH labeling that is sensitive to processing and fixation differences (Mello et al, 1998; Castelino et al, 2007a; Waterman and Harding, 2008).…”

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

“…Immunohistochemistry for DBH positive fibers delineates several song nuclei like HVC, RA, LMAN and Uva (Mello et al, 1998; Waterman and Harding, 2008). Area X has very sparse albeit quantifiable DBH labeling that is sensitive to processing and fixation differences (Mello et al, 1998; Castelino et al, 2007a; Waterman and Harding, 2008). In addition to nuclei of the song system, areas that are important for song production or perception but that lie outside the song control circuit also contain high levels of DBH-immunoreactivity (DBH-ir).…”

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

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What birdsong can teach us about the central noradrenergic system

Castelino¹,

Schmidt²

2010

Journal of Chemical Neuroanatomy

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Increasing evidence indicates that the noradrenergic system plays a key role in biasing the nervous system towards producing behaviors that help animals adapt to constantly changing environments. Most of the studies investigating noradrenergic function are performed in animals that have a limited repertoire of tractable natural behaviors. Songbirds, in contrast, with their rich set of precisely quantifiable vocal behaviors, provide a unique model system to study the noradrenergic system. An additional advantage of this system is the existence of a well-defined neural circuit, known as the song system, that is necessary for the production, learning and perception of song and can be studied at many different levels. These include the ability to investigate the effect of norepinephrine on synaptic function using brain slices, identifying its influence on singing-related gene expression and monitoring its impact on the activity of single neurons recorded in awake behaving birds. In this review article, we describe the similarities and differences, both anatomical and functional, between the avian and mammalian noradrenergic system and its role in sensory processing, learning, attention and synaptic modulation. We also describe how the noradrenergic system influences motor production, an under-explored aspect of norepinephrine function in mammalian studies. We argue that the richness of behaviors observed in songbirds provides a unique opportunity to study the noradrenergic system in a highly integrative manner that will ultimately provide important insights in the role of this system in normal behavior and disease.

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Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

Section: Anatomy Of the Noradrenergic System In Songbirdsmentioning

confidence: 99%

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What birdsong can teach us about the central noradrenergic system

Castelino¹,

Schmidt²

2010

Journal of Chemical Neuroanatomy

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Divergent projections from locus coeruleus to the corticobasal ganglia system and ventral tegmental area of the adult male zebra finch

Alvarado

Hatfield

Mooney

2023

J of Comparative Neurology

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The locus coeruleus (LC) is a small noradrenergic brainstem nucleus that plays a central role in regulating arousal, attention, and performance. In the mammalian brain, individual LC neurons make divergent axonal projections to different brain regions, which are distinguished in part by which noradrenaline (NA) receptor subtypes they express. Here, we sought to determine whether similar organizational features characterize LC projections to corticobasal ganglia (CBG) circuitry in the zebra finch song system, with a focus on the basal ganglia nucleus Area X, the thalamic nucleus DLM, as well as the cortical nuclei HVC, LMAN, and RA. Single and dual retrograde tracer injections reveal that single LC–NA neurons make divergent projections to LMAN and Area X, as well as to the dopaminergic VTA/SNc complex that innervates this CBG circuit. Moreover, in situ hybridization revealed that differential expression of mRNA encoding α2A and α2C adrenoreceptors distinguishes LC‐recipient CBG song nuclei. Therefore, LC–NA signaling in the zebra finch CBG circuit employs a similar strategy as in mammals, which could allow a relatively small number of LC neurons to exert widespread yet distinct effects across multiple brain regions.

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Interference of the noradrenergic neurotoxin DSP4 with neuronal and nonneuronal monoamine transporters

Wenge

Bönisch

2009

Naunyn-Schmied Arch Pharmacol

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The haloalkylamine DSP4 (N[-2-chloroethyl]-N-ethyl-2-bromobenzylamine) is a noradrenergic neurotoxin, which is used for the chemical denervation of noradrenergic neurons, and it has been proposed to be a selective substrate for the neuronal, Na(+)- and Cl(-)-dependent noradrenaline transporter (NAT). In the present study, we investigated whether DSP4 not only interacts with the human NAT (hNAT) but also with other neuronal monoamine transporters such as the transporters for dopamine (hDAT) and serotonin (hSERT) or with nonneuronal (Na(+)-independent) monoamine transporters also known as organic cation transporters (OCTs), such as hOCT(1), hOCT(2), and hOCT(3). Using human embryonic kidney HEK293 cells heterologously expressing the corresponding transporter, we show that DSP4 irreversibly inhibits the hNAT, hDAT, hSERT, and hOCT(3). However, this inhibition includes a reversible component at the hDAT, hSERT, and hOCT(3) but not at the hNAT. The inhibitory potency of DSP4 at the neuronal transporters was highest at the hNAT (IC(50) about 5 microM), and it was about five and 40 times lower at the hSERT and hDAT, respectively. DSP4 inhibited all three hOCTs with high potency (IC(50) about 1 microM) but in a completely reversible manner at hOCT(1) and hOCT(2). Cytotoxicity by 24-h exposure of hNAT- or hOCT-expressing cells to low DSP4 concentrations (<10 microM) could be observed only in hNAT-expressing cells. Thus, DSP4's high-affinity uptake through the NAT together with its completely irreversible mode of interaction with the NAT may contribute to its selectivity as noradrenergic neurotoxin.

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Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches

Cited by 18 publications

References 59 publications

What birdsong can teach us about the central noradrenergic system

What birdsong can teach us about the central noradrenergic system

Divergent projections from locus coeruleus to the corticobasal ganglia system and ventral tegmental area of the adult male zebra finch

Interference of the noradrenergic neurotoxin DSP4 with neuronal and nonneuronal monoamine transporters

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