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Cholinergic neurons in the mouse rostral ventrolateral medulla target sensory afferent areas

Brain Structure and Function volume 218, pages 455–475 (2013)Cite this article

Abstract

The rostral ventrolateral medulla (RVLM) primarily regulates respiration and the autonomic nervous system. Its medial portion (mRVLM) contains many choline acetyltransferase (ChAT)-immunoreactive (ir) neurons of unknown function. We sought to clarify the role of these cholinergic cells by tracing their axonal projections. We first established that these neurons are neither parasympathetic preganglionic neurons nor motor neurons because they did not accumulate intraperitoneally administered Fluorogold. We traced their axonal projections by injecting a Cre-dependent vector (floxed-AAV2) expressing either GFP or mCherrry into the mRVLM of ChAT-Cre mice. Transduced neurons expressing GFP or mCherry were confined to the injection site and were exclusively ChAT-ir. Their axonal projections included the dorsal column nuclei, medullary trigeminal complex, cochlear nuclei, superior olivary complex and spinal cord lamina III. For control experiments, the floxed-AAV2 (mCherry) was injected into the RVLM of dopamine beta-hydroxylase-Cre mice. In these mice, mCherry was exclusively expressed by RVLM catecholaminergic neurons. Consistent with data from rats, these catecholaminergic neurons targeted brain regions involved in autonomic and endocrine regulation. These regions were almost totally different from those innervated by the intermingled mRVLM-ChAT neurons. This study emphasizes the advantages of using Cre-driver mouse strains in combination with floxed-AAV2 to trace the axonal projections of chemically defined neuronal groups. Using this technique, we revealed previously unknown projections of mRVLM-ChAT neurons and showed that despite their close proximity to the cardiorespiratory region of the RVLM, these cholinergic neurons regulate sensory afferent information selectively and presumably have little to do with respiration or circulatory control.

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Abbreviations

7:

Facial motor nucleus

10:

Dorsal motor nucleus of the vagus

12:

Hypoglossal motor nucleus

AAV:

Adeno-associated viral vector

Amb:

Ambiguus nucleus

AP:

Area postrema

CC:

Central canal

ChAT:

Choline acetyltransferase

CHT1:

Choline transporter

Cu:

Cuneate nucleus

cu:

Cuneate fasciculus

DBH:

Dopamine beta-hydroxylase

DC:

Dorsal cochlear nucleus

dlPBN:

Dorsal lateral parabrachial complex

FG:

Fluorogold

GFP:

Green fluorescent protein

Gr:

Gracile nucleus

IC:

Inferior colliculus

ION:

Inferior olivary nucleus

LL:

Lateral lemniscus

LRt:

Lateral reticular nucleus

ml:

Medial lemniscus

mRVLM:

Medial part of the RVLM

PAG:

Periaqueductal gray

PRN:

Pontine reticular formation

py:

Pyramidal tract

pyx:

Pyramidal decussation

RMg:

Raphe magnus

RVLM:

Rostral ventrolateral medulla

scp:

Superior cerebellar peduncle

Sol:

Nucleus of the solitary tract

SON:

Superior olivary nucleus

Sp5C:

Spinal trigeminal nucleus, caudal

Sp5DM:

Spinal trigeminal nucleus, dorsomedial

Sp5I:

Spinal trigeminal nucleus, interpolar

sp5:

Spinal trigeminal tract

st:

Solitary tract

TH:

Tyrosine hydroxylase

Tz:

Nucleus of the trapezoid body

VAChT:

Vesicular acetylcholine transporter

VLMN:

Ventrolateral medullary nucleus (cat)

VMM:

Ventromedial medulla

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Acknowledgments

This work was supported by the following grants from the National Institutes of Health (HL74011 & HL 28785 to PGG).

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  1. Department of Pharmacology, University of Virginia Health System, P.O. Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA, 22908-0735, USA

    Ruth L. Stornetta, Conrad J. Macon, Thanh M. Nguyen, Melissa B. Coates & Patrice G. Guyenet

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  1. Ruth L. Stornetta
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  2. Conrad J. Macon
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  5. Patrice G. Guyenet
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Correspondence to Ruth L. Stornetta.

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Stornetta, R.L., Macon, C.J., Nguyen, T.M. et al. Cholinergic neurons in the mouse rostral ventrolateral medulla target sensory afferent areas. Brain Struct Funct 218, 455–475 (2013). https://doi.org/10.1007/s00429-012-0408-3

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Keywords

  • Medulla oblongata
  • Acetylcholine
  • Somatosensory processing