Evidence that noradrenergic neurons in the A1 and A2 nuclei are lesioned by low doses of 6-OHDA injected into the locus coeruleus

Engelbrecht, A. H. P.; Russell, Vivienne A.; Carstens, Machteld E.; Villiers, A. S. De; Searson, A.; Jaffer, A.; Taljaard, J. J. F.

doi:10.1016/0165-0270(94)90056-6

Cited by 9 publications

(7 citation statements)

References 14 publications

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“…In an attempt to resolve this discrepancy our attention turned to the noradrenergic system, as fibers originating in the locus coeruleus (LC) are the only other source of DA in the vicinity of DH-D1Rs and are found in abundance in DH(Jones and Moore, 1977; Engelbrecht et al, 1994; Xu et al, 1998). Electrical and chemical stimulation to the LC increases NE and DA release in terminating cortical regions (Kawahara et al, 2001; Devoto et al, 2005b, a; Devoto and Flore, 2006).…”

Section: Introductionmentioning

confidence: 99%

CNS Dopamine Transmission Mediated by Noradrenergic Innervation

Smith¹,

Greene²

2012

J. Neurosci.

165

130

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The pre-synaptic source of dopamine in the CA1 field of dorsal hippocampus is uncertain due to an anatomical mismatch between dopaminergic terminals and receptors. We show, in an in vitro slice preparation from C57BL6 male mice, that a dopamine (DA) D1 receptor (D1R) mediated enhancement in glutamate synaptic transmission occurs following release of endogenous DA with amphetamine exposure. It is assumed DA is released from terminals innervating from the ventral tegmental area (VTA) even though DA transporter (DAT) positive fibers are absent in hippocampus, a region with abundant D1Rs. It has been suggested this results from a lack of DAT expression on VTA terminals rather than a lack of these terminals per se. Neither a knockdown of tyrosine hydroxylase (TH) expression in the VTA by THsiRNA, delivered locally, by adeno-associated viral vector, nor localized pharmacological blockade of DAT to prevent amphetamine uptake into DA terminals, has any effect on the D1R synaptic, enhancement response to amphetamine. However, either a decrease in TH expression in the locus coeruleus (LC) or a blockade of the norepinephrine (NE) transporter prevents the DA mediated response, indicating LC terminals can release both NE and DA. These findings suggest noradrenergic fibers may be the primary source of DA release in hippocampus and corresponding DA mediated increase in synaptic transmission. Accordingly, these data imply the LC may have a role in DA transmission in the CNS in response to drugs of abuse, and potentially, under physiological conditions.

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Section: Introductionmentioning

confidence: 99%

CNS Dopamine Transmission Mediated by Noradrenergic Innervation

Smith¹,

Greene²

2012

J. Neurosci.

165

130

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“…First, site variability is unavoidable even following careful microinjection of 6-OHDA into specific brain regions (Gaillet et al, 1993). Second, axons originating from the medullary NA nuclei, i.e., the nucleus of the solitary tract (NTS) and ventrolateral reticular formation (VLR), may also be affected since 6-OHDA is readily taken up by nerve endings and axons en passage (Engelbrecht et al, 1994). DSP-4 destroys the NA terminals originating from the LC with considerable selectivity following systemic administration (Jonsson et al, 1981;Fritschy and Grzanna, 1989).…”

Section: Introductionmentioning

confidence: 99%

Targeting of Locus Ceruleus Noradrenergic Neurons Expressing Human Interleukin-2 Receptor α-Subunit in Transgenic Mice by a Recombinant Immunotoxin anti-Tac(Fv)-PE38: A Study for Exploring Noradrenergic Influence upon Anxiety-Like and Depression-Like Behaviors

Itoi¹,

Sugimoto²,

Suzuki³

et al. 2011

J. Neurosci.

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“…Noradrenergic (NA) neurons are strongly implicated in control of respiratory homeostasis and chemosensitivity (8,69–75), but many prior studies bear methodological caveats such as lack of resolution due to overly broad lesions or injections (76), developmental and non-cell-autonomous compensation after gene mutations, or restraint or anesthesia in vivo (77). Here we show in conscious, unrestrained mice that inhibition of TgDBH-Cre -defined noradrenergic neurons led to significantly reduced tidal volume and minute ventilation following hypercapnic exposure.…”

Section: Discussionmentioning

confidence: 99%

A CRISPR toolbox for generating intersectional genetic mice for functional, molecular, and anatomical circuit mapping

Lusk

McKinney

et al. 2021

Preprint

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Background A full understanding of circuits and cellular mechanisms governing health and disease requires the dissection and multi-faceted study of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic response alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical study. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, the expense and difficulty associated with production of customized intersectional mouse lines have limited widespread application to more common allele manipulations that are often commercially produced at great expense. Results We present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production. Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study how functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle. Conclusions Lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.

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Evidence that noradrenergic neurons in the A1 and A2 nuclei are lesioned by low doses of 6-OHDA injected into the locus coeruleus

Cited by 9 publications

References 14 publications

CNS Dopamine Transmission Mediated by Noradrenergic Innervation

CNS Dopamine Transmission Mediated by Noradrenergic Innervation

Targeting of Locus Ceruleus Noradrenergic Neurons Expressing Human Interleukin-2 Receptor α-Subunit in Transgenic Mice by a Recombinant Immunotoxin anti-Tac(Fv)-PE38: A Study for Exploring Noradrenergic Influence upon Anxiety-Like and Depression-Like Behaviors

A CRISPR toolbox for generating intersectional genetic mice for functional, molecular, and anatomical circuit mapping

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