Elsevier

Neuroscience

Volume 219, 6 September 2012, Pages 48-61
Neuroscience

The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus

https://doi.org/10.1016/j.neuroscience.2012.05.070Get rights and content
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Abstract

Elevated sympathetic nerve activity, strongly associated with cardiovascular disease, is partly generated from the presympathetic neurons of the paraventricular nucleus of the hypothalamus (PVN). The PVN-presympathetic neurons regulating cardiac and vasomotor sympathetic activity receive information about cardiovascular status from receptors in the heart and circulation. These receptors signal changes via afferent neurons terminating in the nucleus tractus solitarius (NTS), some of which may result in excitation or inhibition of PVN-presympathetic neurons. Understanding the anatomy and neurochemistry of NTS afferent connections within the PVN could provide important clues to the impairment in homeostasis cardiovascular control associated with disease. Transynaptic labelling has shown the presence of neuronal nitric oxide synthase (nNOS)-containing neurons and GABA interneurons that terminate on presympathetic PVN neurons any of which may be the target for NTS afferents. So far NTS connections to these diverse neuronal pools have not been demonstrated and were investigated in this study. Anterograde (biotin dextran amine – BDA) labelling of the ascending projection from the NTS and retrograde (fluorogold – FG or cholera toxin B subunit – CTB) labelling of PVN presympathetic neurons combined with immunohistochemistry for GABA and nNOS was used to identify the terminal neuronal targets of the ascending projection from the NTS. It was shown that NTS afferent terminals are apposed to either PVN-GABA interneurons or to nitric oxide producing neurons or even directly to presympathetic neurons. Furthermore, there was evidence that some NTS axons were positive for vesicular glutamate transporter 2 (vGLUT2). The data provide an anatomical basis for the different functions of cardiovascular receptors that mediate their actions via the NTS–PVN pathways.

Highlights

► Ascending NTS fibres target PVN-associated neurons. ► Suggest glutamate as the neurotransmitter. ► Anatomical basis for the different functions of cardiovascular receptors.

Abbreviations

BDA
biotin dextran amine
CTB
cholera B toxin subunit
DAB
diaminobenzidine
FG
fluorogold
GABA
gamma aminobutyric acid
HF
heart failure
HRP
horseradish peroxidase
IP
intraperitoneal
MI
myocardial infarction
NGS
normal goat serum
NHS
normal horse serum
NO
nitric oxide
nNOS
neuronal nitric oxide synthase
NTS
nucleus tractus solitarius
PB
phosphate buffer
PFA
paraformaldehyde
PVN
paraventricular nucleus of the hypothalamus
RVLM
rostral ventrolateral medulla
SPN
sympathetic preganglionic neurons
TBS
Tris buffered saline
vGLUT2
vesicular glutamate transporter 2

Key words

nucleus tractus solitarius
paraventricular nucleus of the hypothalamus
nitric oxide
gamma amino butyric acid
spinally projecting presympathetic neurons

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