targeted-toxins

Clement MK, Pimentel CS, Swaine JA, Pimentel AJ, Hutchins D, McGaughy JA (2019) Dissociable attentional effects of dopaminergic and cholinergic lesions to the anterior cingulate cortex. Neuroscience 2019 Abstracts 418.11. Society for Neuroscience, Chicago, IL.

Summary: Prior work from our lab has shown that excitotoxic lesions to the anterior cingulate cortex (ACC) impairs the ability of rats to filter certain types of distracting stimuli (Newman and McGaughy 2011). Specifically, rats with lesions of the ACC cannot filter distractors that have been made salient through pairing with reinforcement. In contrast, these same subjects can filter distracting stimuli that have not been predictive of reward. The present study investigates the effects of neuromodulator specific lesions of the same region to determine how specific neuromodulators contribute to the attentional function of ACC. Cholinergic or dopaminergic deafferentation of the ACC was achieved using either 192 IgG saporin (n=10) or dopamine transporter saporin (n=10). Lesions were restricted to the rostral portion of the area and did not spread to nearby prefrontal sub-regions e.g prelimbic cortex. After lesioning, subjects were tested in an attentional set-shifting task (Birrell and Brown 2000). While both cholinergic and dopaminergic lesions increased distractibility, these deficits were not as severe as those produced after excitotoxic lesions (n= 8). In contrast to excitotoxic lesions, both cholinergic and dopaminergic lesions also impeded formation of an attentional set. Because dopaminergic lesions produced impairments in many stages of the tasks, we hypothesized that these subjects had a more general impairment in stimulus processing. In order to address these broader processing impairments, we analyzed the data to determine whether lesioned rats showed more sensitivity to novel stimuli, or made more perseverative errors. The implications of these data for understanding the unique contributions of acetylcholine and dopamine to attentional processing in the ACC will be discussed.

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DAT-SAP (Cat. #IT-25)

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.

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

Kucinski A, Phillips KB, Koshy Cherian A, Sarter M (2020) Rescuing the attentional performance of rats with cholinergic losses by the M1 positive allosteric modulator TAK-071. Psychopharmacology (Berl) 237(1):137-153. doi: 10.1007/s00213-019-05354-5 PMID: 31620809

Related Products: 192-IgG-SAP (Cat. #IT-01)

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.

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

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.

Murillo-Rodríguez E, Millán-Aldaco D, Palomero-Rivero M, Morales-Lara D, Mechoulam R, Drucker-Colín R (2019) Cannabidiol partially blocks the excessive sleepiness in hypocretindeficient rats: Preliminary data. CNS Neurol Disord Drug Targets 18(9):705-712. doi: 10.2174/1871527318666191021143300

Objective: To determine whether the systemic injection of CBD (5 mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model.

Summary: Preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.

Usage: Orexin-SAP (490 ng/0.5 μL, n= 10) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Verkhratsky A, Parpura V, Rodriguez-Arellano J, Zorec R (2019) Astroglia in Alzheimer’s Disease. (eds. Verkhratsky A, Ho M, Zorec R, Parpura V). In: Advances in Experimental Medicine and Biology: Neuroglia in Neurodegenerative Diseases. 1175:273-324. Springer, Singapore. doi: 10.1007/978-981-13-9913-8_11

Summary: A review of the tools for creating animal models of Alzheimer’s Disease. 192-IgG-SAP binds selectively and irreversibly to low-affinity nerve growth factor receptor interrupting cholinergic neuronal protein synthesis was employed. Anti-DBH-SAP binds dopamine-β-hydroxylase, which is not only localized mainly in the cytosol, but also at the plasma membrane surface of noradrenergic neurons. Anti-DBH-SAP produced specific and dose-dependent depletions of locus coeruleus neurons, with no effects on other cholinergic, dopaminergic or serotonergic neuronal populations. The possibility to induce a partial or total noradrenergic loss (by varying the injected dose) makes this immunotoxic approach an ideal model to study events within the noradrenergic projection system, as they occur during age-related demise of locus coeruleus in humans.

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)

Phillips K (2019) Micro- and macro-psychological analyses of attention and the role of cholinergic systems. University of Michigan Thesis. doi: 2027.42/151673

Objective: To determine the validity of behavioral tasks used to reveal neurobehavioral and neurocognitive mechanisms of attention.

Summary: The opposing cognitive-motivational styles of sign-trackers and goal-trackers, while originating in different approaches to food and drug cues, provide us with a crucial insight into the individual differences and specific vulnerabilities for attentional processing and performance.

Usage: Bilateral bolus infusions of 192-IgG-SAP (0.8 μl/hemisphere).

Related Products: 192-IgG-SAP (Cat. #IT-01)

Seamon M, Ahn W, Li AJ, Ritter S, Harris RBS (2019) Leptin receptor-expressing neurons in ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions. Am J Physiol Endocrinol Metab 317(4):E586-E596. doi: 10.1152/ajpendo.00205.2019

Objective: To test the importance of VMH leptin responsiveness in mediating weight loss caused by fourth ventricle leptin infusion.

Summary: Leptin did not inhibit food intake and respiratory exchange ratio in rats treated with Leptin-SAP. VMH leptin receptors do not play a significant role in maintaining energy balance in basal conditions, but limit weight gain during positive energy balance.

Usage: Bilateral VMH 75-nl injections of 260 ng/ml of Leptin-SAP or Blank-SAP.

Related Products: Leptin-SAP (Cat. #IT-47), Blank-SAP (Cat. #IT-21)

Pan H, Fatima M, Li A, Lee H, Cai W, Horwitz L, Hor CC, Zaher N, Cin M, Slade H, Huang T, Xu XZS, Duan B (2019) Identification of a spinal circuit for mechanical and persistent spontaneous itch. Neuron 103(6):1135-1149.e6. doi: 10.1016/j.neuron.2019.06.016

Objective: To identify a spinal circuit for mechanical and persistent spontaneous itch.

Summary: Findings indicate excitatory interneurons expressing Urocortin 3::Cre (Ucn3+) in the dorsal spinal cord as a valid cellular target for future therapeutic interventions against chronic itch, without affecting normal touch.

Usage: To ablate spinal GRPR+ neurons, mice were given a single intrathecal injection of either Bombesin-SAP or Blank-SAP (400 ng in 10 mL sterile saline). To ablate spinal Npra+ neurons, mice were given a single intrathecal injection of either Nppb-SAP or Blank-SAP (5 mg in 10 mL sterile saline).

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21)

Katsurada K, Nakata M, Saito T, Zhang B, Maejima Y, Nandi SS, Sharma NM, Patel KP, Kario K, Yada T (2019) Central glucagon-like peptide-1 receptor signaling via brainstem catecholamine neurons counteracts hypertension in spontaneously hypertensive rats. Sci Rep 9(1):12986. doi: 10.1038/s41598-019-49364-x

Objective: To determine mechanisms for antihypertensive effect of GLP-1R agonists.

Summary: The central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity.

Usage: Anti-DBH-SAP or Blank-SAP was injected into NTS bilaterally (6 ng/200 nl).

Related Products: Anti-DBH-SAP (Cat. #IT-03), Blank-SAP (Cat. #IT-21)