Souza GMPR, Stornetta RL, Stornetta DS, Abbott SBG, Guyenet PG (2019) Contribution of the retrotrapezoid nucleus and carotid bodies to hypercapnia- and hypoxia-induced arousal from sleep. J Neurosci 39(49):9725-9737. doi: 10.1523/JNEUROSCI.1268-19.2019

Objective: To examine the contribution of two lower brainstem nuclei that could be implicated in CO2 and hypoxia-induced arousal.

Summary: RTN, a brainstem nucleus that mediates the effect of brain acidification on breathing, also contributes to arousal elicited by CO2 but not hypoxia.

Usage: To ablate the retrotrapezoid nucleus (RTN), SSP-SAP was administered (2.4 ng) through bilateral injections via a dorsal craniotomy.

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Díaz HS, Andrade DC, Toledo C, Lucero C, Arce-Álvarez A, Del Rio R (2019) Episodic stimulation of central chemoreflex elicits long-term breathing disorders and autonomic imbalance in heart failure rats. Eur Respir J 54(suppl 63):OA4936. doi: 10.1183/13993003.congress-2019.OA4936

Objective: To determine the role of CC in the development of cardiorespiratory dysfunction in a HF model.

Summary: Rats were exposed to pisodic hypercapnic stimulation (EHS) The effects of EHS in rats with heart failure were attenuated by SSP-SAP treatment.

Usage: Selective destruction of chemoreceptor neurons within the retrotapezoid nucleus (RTN) was performed via SSP-SAP injections (0.6 ng/30 nL).

Related Products: SSP-SAP (Cat. #IT-11)

Wang S, Kim M, Ong K, Pae E-K, Chung M-K (2019) Nociceptors expressing TRPV1 and trigeminal nucleus neurons expressing NK1 mediate orthodontic pain. Neuroscience 2019 Abstracts 052.10. Society for Neuroscience, Chicago, IL.

Summary: Orthodontic force produces mechanical irritation and inflammation in periodontium, which inevitably accompanies pain. Despite its high prevalence, treatment of orthodontic pain is not effective. Determining detailed neural mechanisms involving peripheral and central nervous system should be critical to improve the management of orthodontic pain. Periodontal ligament is projected by peptidergic nociceptors, which is enriched with transient receptor potential vanilloid 1 (TRPV1), a receptor for capsaicin. Trigeminal subnucleus caudalis (Vc), is critical for relaying orofacial nociceptive signal into brain. A group of second- order neurons in the superficial dorsal horn of Vc express neurokinin 1 receptor (NK1), a receptor for substance P, and receive inputs from peptidergic nociceptors. However, the contribution of these nociceptive neurons to orthodontic pain has not been determined. Orthodontic force of 10g produced reliable tooth movement in mice. Orthodontic pain was evaluated by measuring mouse grimace scale (MGS) and bite force (BF), which could represent spontaneous pain and chewing-evoked pain, respectively. Orthodontic force increased MGS and decreased BF, which peaked at 1d and returned near to sham level at 7d. Using targeted chemical ablation of specific subsets of neurons, we determined the contribution of TRPV1+ nociceptors and NK1+ Vc neurons to orthodontic pain behaviors in mice. Ablation of TRPV1+ nociceptors by injecting resiniferatoxin into trigeminal ganglia significantly attenuated orthodontic force assessed by MGS and BF. Chemical ablation of NK1+ Vc neurons by injecting saporin conjugated with substance P into Vc also significantly reduced the extent of changes in MGS and BF by orthodontic force. These results suggest that TRPV1+ trigeminal nociceptors and NK1+ Vc neurons constitute a major neural pathway for transmission of orthodontic pain, which is a fundamental neural mechanism of orthodontic pain transmission. The new mouse model of orthodontic pain will be useful for mechanistic study to develop novel approaches for painless orthodontics.

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Truckenbrod LM, Bumanglag AV, Chun E, Hernandez A, Federico QP, Maurer AP, Sloviter RS, Burke SN (2019) Targeted hippocampal GABA neuron ablation produces hippocampal sclerosis, epilepsy, and dissociable effects on the Morris water maze and object-place paired association tasks. Neuroscience 2019 Abstracts 158.03. Society for Neuroscience, Chicago, IL.

Summary: An epileptogenic role for hippocampal GABAergic dysfunction has recently been reported (Chun et al. 2019). Specifically, selective ablation of hippocampal GABA neurons by Stable Substance P-saporin (SSP-saporin) conjugate caused dorsal hippocampal sclerosis and chronic epilepsy, without involving convulsive status epilepticus or widespread brain injury. The current study assessed cognitive function in chronically epileptic SSP-saporin-treated rats and their vehicle-injected controls ~8 months following injection. First, rats completed the Morris Water Maze test of spatial learning and memory (Morris et al., 1982). Animals then underwent testing with the object-place paired association (OPPA) task, which requires the hippocampus as well as functional connectivity between the hippocampus and cortical areas (Jo and Lee, 2010; Hernandez et al., 2017), and then a simple object discrimination task. Interestingly, both controls and rats with dorsal hippocampal sclerosis and chronic epilepsy were able to learn the location of the hidden platform in the Morris Water Maze task and could also acquire a simple pair-wise object discrimination. However, epileptic rats with dorsal hippocampal sclerosis were significantly impaired on the OPPA task, which requires animals to integrate spatial location memory with a correct object choice and is a more sensitive measure of cognitive dysfunction (Hernandez et al., 2015). These data indicate that, similar to humans with medial temporal lobe epilepsy, selective hippocampal sclerosis and epilepsy in this model do not result in global cognitive decline. Rather, cognitive functions that require functional connectivity between the hippocampus and cortical areas are selectively affected.

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See Also:

• Chun E et al. Targeted hippocampal GABA neuron ablation by stable substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats. Epilepsia 60(5):e52-e57, 2019.

Guyenet PG, Stornetta RL, Souza GMPR, Abbott SBG, Shi Y, Bayliss DA. (2019) The retrotrapezoid nucleus: Central chemoreceptor and regulator of breathing automaticity. Trends Neurosci 42(11):807-824. doi: 10.1016/j.tins.2019.09.002

Summary: This review describes the neurons of the retrotrapezoid nucleus (RTN), their transcriptome, developmental lineage, and anatomical projections. The authors also review their contribution to CO2 homeostasis and to the regulation of breathing automaticity during sleep and wake.

Usage: Local injection of SSP-SAP to kill RTN neurons.

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Wercberger R, Basbaum AI (2019) Spinal cord projection neurons: A superficial, and also deep, analysis. Curr Opin Physiol 11:109-115. doi: 10.1016/j.cophys.2019.10.002

Summary: Modern approaches to map complex neural circuits require knowledge of the molecular language that defines cell type specificity. However, with few exceptions, NK1R remains the marker consistently used to define projection neurons and even to interrogate their contribution to pain and itch (Mantyh et al.) The first of two studies demonstrating that SP-SAP-mediated ablation of dorsal horn NK1R-expressing neurons reduces injury-induced hyperalgesia. (Carstens et al.) In this paper SP-SAP-mediated ablation of dorsal horn NK1R-expressing neurons reduced pruritogen-evoked scratching.

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See Also:

• Mantyh PW et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279, 1997.
• Carstens EE et al. Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. Neuroreport 21:303-308, 2010.

Araldi D, Bogen O, Green PG, Levine JD (2019) Role of nociceptor toll-like receptor 4 (TLR4) in opioid-induced hyperalgesia and hyperalgesic priming. J Neurosci 39(33):6414-6424. doi: 10.1523/JNEUROSCI.0966-19.2019

Objective: To evaluate the hypothesis that hyperalgesia and priming induced by opioids are mediated by similar nociceptor mechanisms.

Summary: Treatment with isolectin B4 (IB4)-saporin or SSP-saporin (which deplete IB4! and peptidergic nociceptors, respectively), or their combination, prevented systemic LDM-induced hyperalgesia, but not priming. HDM-induced priming, but not analgesia, was markedly attenuated in both saporin-treated groups.

Usage: IB4-SAP was diluted in saline and a dose of 3.2 μg in a volume of 20 μl administered intrathecally. SSP-SAP was diluted in saline and a dose of 100 ng in a volume of 20 μl was administered intrathecally.

Related Products: IB4-SAP (Cat. #IT-10), SSP-SAP (Cat. #IT-11)

Acton D, Ren X, DiCostanzo S, Dalet A, Bourane S, Bertocchi I, Eva C, Goulding M (2019) Spinal neuropeptide Y1 receptor-expressing neurons form an essential excitatory pathway for mechanical itch. Cell Reports 28(3):625-639.e6 . doi: 10.1016/j.celrep.2019.06.033

Objective: To determine the central pathway for mechanical itch.

Summary: NPY-Y1 signaling regulates the transmission of innocuous tactile information by establishing biologically relevant thresholds for touch discrimination and mechanical itch reflexes. Neither the evoked nor spontaneous scratching seen following activation of Y1Cre neurons was affected by ablation of the GRPR+ neurons. NK1R+ neuron ablation failed to modulate mechanically evoked itch.

Usage: P28 mice were given a single intrathecal (i.t.) injection of either Bombesin-SAP (400 ng in 5 mL 0.9% sterile saline) to ablate GRPR+ cells or SSP-SAP to ablate NK1r+ neurons (100 ng in 5 mL 0.9% sterile saline). Littermate controls received Blank-SAP (equal mass in 5 mL 0.9% sterile saline).

Related Products: Bombesin-SAP (Cat. #IT-40), SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Chun E, Bumanglag AV, Burke SN, Sloviter RS (2019) Targeted hippocampal GABA neuron ablation by stable substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats. Epilepsia 60(5):e52-e57. doi: 10.1111/epi.14723

Objective: Hippocampal GABA neurons were targeted for selective elimination to determine whether a focal hippocampal GABAergic defect in an otherwise normal brain can initiate cryptogenic temporal lobe epilepsy with hippocampal sclerosis.

Summary: Hippocampal GABAergic dysfunction is epileptogenic and can produce the defining features of cryptogenic temporal lobe epilepsy.

Usage: Intrahippocampal injections of SSP-SAP (0.4 ng/10 nL) were performed using a 0.5-μL Neuros Syringe lowered into four hippocampal sites along both the transverse and longitudinal hippocampal axes bilaterally.

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Read the featured article in Targeting Trends.

Souza G, Stornetta R, Stornetta D, Abbott S, Guyenet P (2019) Contribution of retrotrapezoid nucleus and carotid bodies to asphyxia‐induced arousal in rats. FASEB J 33(1):733.6. Experimental Biology 2019 Meeting Abstracts doi: 10.1096/fasebj.2019.33.1_supplement.733.6

Objective: To determine whether the retrotrapezoid nucleus (RTN) is implicated in CO2-induced arousal.

Summary: The authors confirm the importance of the CBs to hypoxia-induced arousal and demonstrate that arousal to hypercapnia is selectively reduced after RTN lesion.

Usage: RTN was nearly completely destroyed with microinjections of SSP-SAP (2.4 ng).

Related Products: SSP-SAP (Cat. #IT-11)