References

Xu C, Michelsen KA, Wu M, Morozova E, Panula P, Alreja M (2004) Histamine innervation and activation of septohippocampal GABAergic neurones: Involvement of local ACh release. J Physiol 561(Pt 3):657-670. doi: 10.1113/jphysiol.2004.071712 PMID: 15486020

Related Products: 192-IgG Mouse Monoclonal, Cy3-labeled (Cat. #AB-N43FL3)

Jonasson Z, Cahill JF, Tobey RE, Baxter MG (2004) Sexually dimorphic effects of hippocampal cholinergic deafferentation in rats. Eur J Neurosci 20(11):3041-3053. doi: 10.1111/j.1460-9568.2004.03739.x

Summary: Studies of cholinergic neuron lesions have been performed almost exclusively in male animals. In this work, the authors examined the differences of cholinergic lesions between males and females. Rats were treated with four injections totaling 0.15 µg of 192-Saporin (Cat. #IT-01) into the medial septum/vertical limb of the diagonal band. The results demonstrate differences in learning and memory processes between male and female rats.

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

Hodges MR, Opansky C, Qian B, Davis S, Bonis J, Bastasic J, Leekley T, Pan LG, Forster HV (2004) Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe-area in awake goats. J Appl Physiol 97(6):2236-2247. doi: 10.1152/japplphysiol.00584.2004

Summary: The authors wished to investigate the influence medullary raphe-area neurons have on breathing. This control may be through CO2/H+ chemoreceptors and/or through non-chemoreceptor modulation. 1 or 10 µl of 50 pM SP-SAP (Cat. #IT-07) or Saporin (Cat. #PR-01) was injected into the raphe of goats. Breathing and CO2 sensitivity were evaluated during different physiologic conditions. The data suggest that SP receptor- and glutamate receptor-expressing neurons in the medullary raphe both influence CO2 sensitivity, but not altered breathing periods.

Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)

Ma J, Shen B, Rajakumar N, Leung LS (2004) The medial septum mediates impairment of prepulse inhibition of acoustic startle induced by a hippocampal seizure or phencyclidine. Behav Brain Res 155(1):153-166. doi: 10.1016/j.bbr.2004.04.010

Summary: Deficits in sensorimotor gating, suppression of a motor response by a sensory stimulus are found in schizophrenic patients, as well as laboratory animals after administration of compounds such as phencyclidine (PCP). The authors lesioned the cholinergic system of the medial septum in rats with 0.14-0.21 µg injections of 192-Saporin (Cat. #IT-01) to examine the involvement of these neurons in sensorimotor gating. The authors suggest that GABAergic, but not cholinergic septohippocampal neurons mediate this deficit.

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

Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28(7):771-784. doi: 10.1016/j.neubiorev.2004.09.006

Objective: To review current progress in our understanding of the rodent prefrontal cortex, especially evidence for functional divergence of the anatomically distinct sub-regions of the rat prefrontal cortex.

Summary: A greater understanding of the prefrontal cortex will come from using tasks that load specific cognitive and executive processes, in parallel with discovering new ways of manipulating the different sub-regions and neuromodulatory systems of the prefrontal cortex.

Usage: Lesions of the cortically projecting cholinergic neurons of the nucleus basalis magnocellularis made using excitotoxins, or the highly selective cholinergic immunotoxin 192 IgG-SAP, generally impair discriminative performance.

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

See Also:

• Heckers S et al. Complete and selective cholinergic denervation of rat neocortex and hippocampus but not amygdala by an immunotoxin against the p75 NGF receptor. J Neurosci 14:1271-1289, 1994.

Estacio MA, Tsukamura H, Reyes BA, Uenoyama Y, I’anson H, Maeda K (2004) Involvement of brainstem catecholaminergic inputs to the hypothalamic paraventricular nucleus in estrogen receptor alpha expression in this nucleus during different stress conditions in female rats. Endocrinology 145(11):4917-4926. doi: 10.1210/en.2004-0469

Summary: Norepinephrine release in the paraventricular nucleus (PVN) is increased during periods of metabolic stress. The authors hypothesized that noradrenergic inputs to the PVN may also mediate estrogen receptor a (ERa) expression in the PVN during metabolic stress. 20 ng of Anti-DBH-SAP (Cat. #IT-03) was injected bilaterally into the PVN of rats, and ERa expression was examined in several stress models. Results indicate that during metabolic stress catecholaminergic inputs to the PVN play a major role in mediating the induction of ERa expression.

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

Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV (2004) Large lesions in the pre-Botzinger complex area eliminate eupneic respiratory rhythm in awake goats. J Appl Physiol 97(5):1629-1636. doi: 10.1152/japplphysiol.00953.2003

Summary: Previously the authors demonstrated that lesioning the pre-Bötzinger Complex (pre-BötzC) with SP-SAP (Cat. #IT-07) resulted in transient disruptions of normal respiratory muscle activation in goats. The purpose of this study was to examine the effects of a more complete lesion of the pre-BötzC area. The authors treated SP-SAP-lesioned goats with ibotenic acid. The results suggest that the pre-BötzC is critical for generating a normal respiratory rhythm during the awake state.

Related Products: SP-SAP (Cat. #IT-07)

Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, Forster HV (2004) Small reduction of neurokinin-1 receptor-expressing neurons in the pre-Botzinger complex area induces abnormal breathing periods in awake goats. J Appl Physiol 97(5):1620-1628. doi: 10.1152/japplphysiol.00952.2003

Summary: Previous work has shown that lesion of the pre-Bötzinger Complex (pre-BötzC) of rats with SP-SAP (Cat. #IT-07) results in hypoventilation and an abnormal breathing pattern. The authors used 1 or 10 µl of 50 pM SP-SAP bilaterally injected into the pre-BötzC area to further investigate this system in goats. The results show transient changes in respiratory rhythm and respiratory muscle activation patterns, indicating that SP receptor-expressing neurons in the pre-BötzC are involved in the regulation of respiration.

Related Products: SP-SAP (Cat. #IT-07)

Zhou D, Levin BE (2004) PVN anti-SERT-SAP injections reduce body weight gain, normal and glucoprivic feeding, and hypoglycemia- and stress-induced corticosterone responses. Neuroscience 2004 Abstracts 893.14. Society for Neuroscience, San Diego, CA.

Summary: Hindbrain serotonin (5HT) neurons are highly ramified with single neurons innervating several forebrain and hypothalamic areas such as the paraventricular nucleus (PVN). To assess their importance in the regulation of energy homeostasis and hypothalamo-pituitary-adrenal activation, anti-SERT-SAP (SS), an antibody to the 5HT re-uptake transporter (SERT) conjugated to a ribosomal toxin saporin (SAP), was injected bilaterally into the PVN of rats to selectively destroy hypothalamically-projecting 5HT neurons. Unconjugated SAP injections served as controls. SS injections significantly destroyed rostral dorsal (DRa) and medial raphe (MRa) 5HT neurons. Compared to SAP rats, SS rats had 13% lower food intake (SAP 71.2+3.2g vs. SS 61.7+2.8g, P=0.037) and 44% lower body weight gain (SAP 26.9+2.9g vs. SS 15.3+.31g, P=0.003) over 8d. Food intake over 24h (but not 3h) after insulin-induced hypoglycemia was 22% lower in SS (25.1±1.2g) than SAP rats (32.2±0.9g, P<0.01) and their blood glucose levels dropped more during 120min of hypoglycemia (AUC, -3945+77mg/dl) than SAP controls (-3675+108; P=0.01) suggesting a counterregulatory defect. This was supported by a 39% lower 30min corticosterone (Cort) response to hypoglycemia in SS (126±25µg/ml) vs. SAP controls (208±21 μg/ml, P<0.05). On the other hand, the glucagon response to hypoglycemia did not differ between SS (81.3±10.1pg/ml) and SAP-injected rats (65.8±7.6pg/ml; P=0.72). Finally, SS injections reduced the Cort response to 30min immobilization stress (SS 389±21 vs. SAP 460±25 µg/mg; P<0.05) by 15% without significantly affecting basal levels (SS 18.0±3.9 vs. SAP 10.1±2.2 µg/ml, P=0.09). Thus, DRa and MRa 5HT projections to the forebrain play a significant role in energy homeostasis, hypoglycemia-induced feeding and the Cort responses to both hypoglycemia and stress.

Related Products: Anti-SERT-SAP (Cat. #IT-23)

Bugarith KH, Li A, Dinh TT, Ritter S (2004) Injection of the targeted-toxin, neuropeptide Y-saporin (NPY-SAP), into the basomedial hypothalamus (BMH) disrupts leptin and ghrelin signaling. Neuroscience 2004 Abstracts 893.17. Society for Neuroscience, San Diego, CA.

Summary: NPY-SAP, a conjugate of the peptide NPY and saporin, a ribosomal inactivating toxin, specifically lesions NPY receptor-expressing cells. We injected NPY-SAP into the BMH and examined the effects of various inhibitory (leptin, 5ug/5ul/day, icv; GLP-1, 5ug/5ul, icv, CCK, 4ug/kg, ip;) and stimulatory (ghrelin, 2ug/5ul, icv; NPY, 500ng/100nl, icv; 2-DG, 100, 200 and 400 mg/kg; MA, 68mg/kg, ip) peptide and metabolic signals that influence food intake. We also examined the effect of NPY-SAP on NPY, CART and AGRP mRNA expression in NPY/AGRP and POMC/CART neurons known to express the NPY receptor, and the effect of NPY and NPY Y1 receptor immunoreactivity in the arcuate (Arc) nucleus. We found that the anorectic effects of leptin and the orexigenic effects of ghrelin were abolished by NPY-SAP. The stimulation of feeding induced by NPY, 2-DG and MA, and the suppression of deprivation-induced feeding by GLP-1 and CCK were not attenuated by NPY-SAP injection. There was a profound but localized reduction of NPY Y1 receptor-, and NPY fiber and terminal immunoreactivity, and NPY, AGRP and CART mRNA expression in the Arc. NPY-SAP did not appear to be retrogradely transported in hindbrain NPY neurons with hypothalamic terminals. Leptin and ghrelin are thought to act primarily on Arc NPY/AGRP and POMC/CART neurons to mediate their ingestive effects, whereas the effects of 2-DG, MA, CCK and GLP-1 are thought to be mediated in part by mechanisms outside the Arc. Present results show that BMH injections of NPY-SAP selectively impair controls mediated by Arc neural circuitry without causing widespread disruption of other ingestive behaviors. Results also reveal important ingestive controls that do not require Arc NPY/AGRP and POMC/CART neurons.

Related Products: NPY-SAP (Cat. #IT-28)