Targeting Tools: Mouse-Specific p75 Immunotoxin

The long-sought mouse cholinergic toxin has been found! The mouse cholinergic immunotoxin (Cat. #IT-16) is being released for sale at the Society for Neuroscience meeting in New Orleans, November 4-9, 2000! For years ATS has received requests for a molecule that would eliminate cholinergic neurons in the basal forebrain of mice in a manner that 192-Saporin does in the rat. Because of the increasing importance of the mouse in understanding behavioral systems such as learning, memory and attention, there has been a constant interest in a molecule that could do the work. For instance, many transgenic models have given new insights into our understanding of Alzheimer’s Disease (AD), but few of them offered a clear neurodegeneration of one of the most important symptoms: cholinergic denervation. In 1995, ATS, in collaboration with Dr. Joanne Berger-Sweeney of Wellesley College, began its search for the elusive mouse p75 cholinergic toxin. The expression of p75, the low affinity neurotrophin receptor, on the surface of cholinergic basal forebrain (CBF) neurons provided an opportunity to target these neurons in the mouse, just as we had done in the rat. Conjugation of an antibody that targets p75 to saporin has produced a cytotoxin that eliminates the CBF neurons while sparing neighboring neurons that express GAD, calbindin and parvalbumin. Differences between the mouse cholinergic toxin and the rat version, and methods to use the toxin can be discussed with the experts at the ATS booth at the Society for Neuroscience meeting. We also recommend visiting the poster at the Society for Neuroscience meeting that describes the properties and activities of the new immunotoxin: A Specific Cholinergic Immunotoxin in Mice, J.E. Berger-Sweeney, S.L. Murg, M.G. Baxter, N.A. Stearns, D.A. Lappi, Abstract ID 4342, Nov 7, 2000 1:00 – 2:00 PM, Hall G-J.

Targeting Talk: Second Immunotoxins

What is a second immunotoxin?

ATS’s second immunotoxins are conjugations of a secondary antibody (as of December 2000, either goat anti-mouse IgG or goat anti-rabbit IgG) to the ribosome-inactivating protein, saporin.

How does a second immunotoxin target?

The second immunotoxin uses the secondary antibody to “piggyback” onto your primary antibody in order to evaluate the ability of the primary antibody to internalize.

What happens when the second immunotoxin gets inside the cell?

If the second immunotoxin is internalized, saporin will inactivate the ribosomes of the cell, thereby causing cell death.

Are there different types of second immunotoxins available?

As of December 2000, ATS has two products available. 1) Mab-ZAP (Cat. #IT-04) that recognizes mouse primary antibody, and 2) Rab-ZAP (Cat. #IT-05) that recognizes rabbit primary antibody.

What is the ratio of antibody to second immunotoxin for in vitro testing?

Both Mab-ZAP and Rab-ZAP have been shown effective in concentrations ranging from 0.5 to 2 moles of primary antibody per mole of second immunotoxin.

See also: Second Immunotoxins Catalog

Targeting Topics 00q4

Impaired acquisition of a Morris water maze task following selective destruction of cerebellar purkinje cells with OX7-saporin.

Gandhi CC, Kelly1 RM, Wiley RG, Walsh TJ.

Behav Brain Res 109(1):37-47, 2000. PMID: 10699656

The cerebellum has been associated with the control of motor activity and voluntary movements. Recent data have shown the cerebellum may also play a role in “higher order” processes such as learning, language, and cognition. Using 2 μg OX7-SAP (Catalog #IT-02) by i.c.v. injection, Gandhi et al. selectively eliminated Purkinje cells in rat cerebellum in order to examine the ability of treated animals to complete a water maze task. Elimination of these cells significantly impaired the ability of the rats to complete the task, suggesting the cerebellum is involved in learning.

Ectopic noradrenergic hyperinnervation does not functionally compensate for neonatal forebrain acetylcholine lesion.

Pappas BA, Nguyen T, Brownlee B, Tanasoiu D, Fortin T, Sherren N.

Brain Res 867(1-2):90-99, 2000. PMID: 10837801

Removal of cholinergic forebrain neurons in the neonatal rat causes an ingrowth of hippocampal material to the affected area. The behavioral effect of this treatment increases working, but not reference memory errors on the radial arm maze. Pappas et al. used 300 ng 192-Saporin (Catalog #IT-01) by i.c.v. injection to lesion the forebrain of 1- to 3-day old rats coupled with a 6-OHDA lesion to remove hippocampal ingrowths in order to investigate whether these neurons can compensate for cholinergic function in memory. Their results indicate noradrenergic neurons from the hippocampus do not functionally compensate for loss of CBF neurons even though losses of these neurons did not drastically affect the behavior of these animals.

NGF-mediated alteration of NF-kappaB binding activity after partial immunolesions to rat cholinergic basal forebrain neurons.

Gu Z, Toliver-Kinsky T, Glasgow J, Werrbach-Perez K, Perez-Polo JR.

Int J Dev Neurosci 18(4-5):455-468, 2000. PMID: 10817930

After injecting 1.3 μg 192-Saporin (Catalog #IT-01) into the lateral ventricle of rat brain, followed by infusion of NGF antibody, Gu et al. report changes in the activity of the transcription factor NF-κB. Aged rodent brains show an increase in NF-κB activity. This model creates a tool to investigate decreased cholinergic function that is often associated with memory loss and cognitive deficits in the elderly and particularly in patients with Alzheimer’s disease.

Sustained visual attention performance-associated prefrontal neuronal activity: evidence for cholinergic modulation.

Gill TM, Sarter M, Givens B.

J Neurosci 20(12):4745-4757, 2000. PMID: 10844044

Preliminary evidence suggests that demands on attention levels are associated with changes in levels of cortical acetylcholine. Gill et al. used.05 μg 192-Saporin (Catalog #IT-01) by intracortical infusion to demonstrate the role cholinergic neurons play in the ability of rats to pay attention. The researchers monitored medial prefrontal cortex (MPC) activity in the rat brain before and after elimination of cholinergic neurons with 192-Saporin. The results suggest that the cholinergic inputs to the MPC influence the increases of neuronal activity associated with paying attention.

Preferential destruction of cerebellar Purkinje cells by OX7-saporin.

Angner RT, Kelly RM, Wiley RG, Walsh TJ, Reuhl KR.

Neurotoxicology 21(3):395-403, 2000. PMID: 10894129

Purkinje cells function as inhibitors and are the sole output of the cerebellar cortex. Angner et al. eliminate these cells in rats with 1-2 μg OX7-SAP (Catalog #IT-02), an immunotoxin that binds the Thy 1.1 antigen. The treated rats show effects of loss of inhibitory control, including a time-dependent increase in motor activity and decreased motor coordination.

Immunolocalization of the cocaine- and antidepressant-sensitive l-norepinephrine transporter.

Schroeter S, Apparsundaram S, Wiley RG, Miner LH, Sesack SR, Blakely RD.

J Comp Neurol 420(2):211-232, 2000. PMID: 10753308

Norepinephrine transporters are involved in the response to multiple antidepressants and psychostimulants, but the expression of these proteins has not yet been characterized in the central nervous system. Schroeter et al. used an antibody to a cytoplasmic epitope of norepinephrine transporters to map the transporters to noradrenergic neuronal somata, axons, and dendrites. To verify the specificity of the antibody the researchers injected 10 μg of anti-DBH- SAP (Catalog #IT-03) in the left lateral ventricle of rats to destroy the noradrenergic neurons, confirming the specificity of the norepinephrine transporter antibody. Treatment with anti-DBH-SAP completely removed norepinephrine transporter immunoreactivity.

Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats.

Ferencz I, Leanza G, Nanobashvili A, Kokaia M, Lindvall O.

Eur J Neurosci 12(6):2107-2116, 2000. PMID: 10886350

Cholinergic mechanisms have been implicated in human epilepsy, possibly in the role of seizure suppression. Ferencz et al. used 2.5 μg 192-Saporin (Catalog #IT-01) by i.c.v. injection to investigate the effect of eliminating cholinergic projections to the hippocampal formation and cerebral cortex on the induction of epilepsy through electrical stimulation of the rat brain. The researchers used the specificity of 192-Saporin to determine that the loss of specific projections to the amygdala accelerates development of seizures. The hippocampus does not influence this process.

Repeated immunolesions display diminished stress response signal.

Gu Z, Yu J, Werrbach-Perez K, Perez-Polo JR.

Int J Dev Neurosci 18(2-3):177-183, 2000. PMID: 10715572

Cholinergic neurons in the basal forebrain are involved in neurotrophin release in general injury response although this response is impaired in the aged individual. Addition of pharmacological doses of NGF can repair this mechanism. Gu et al. used 192-Saporin (Catalog #IT-01) to model the endogenous stimulation of NGF in response to injury. They found that a one-time administration of 192-Saporin was more effective than chronic repeated administrations for inducing an increase in NGF levels. These results indicate that chronic lesions may cause a desensitization that differs from the acute toxic model.

Cholinergic excitation of septohippocampal GABA but not cholinergic neurons: implications for learning and memory.

Wu M, Shanabrough M, Leranth C, Alreja M.

J Neurosci 20(10):3900-3908, 2000. PMID: 10804229

It has long been assumed that the drug- induced enhancement of learning and memory in both young and aged rats was accomplished through a cholinergic pathway in the hippocampus. Wu et al. used a fluorescent labeling molecule, 192-IgG conjugated to Cy3 (Custom Service from ATS) to visualize these neurons. They found that the effects of cognition-enhancing drugs are not facilitated through action on cholinergic neurons. Instead, activation of GABA neurons is implicated in this model.

Attenuation of the bidirectional effects of chlordiazepoxide and FG 7142 on conditioned response suppression and associated cardiovascular reactivity by loss of cortical cholinergic inputs.

Stowell JR, Berntson GG, Sarter M.

Psychopharmacology (Berl) 150(2):141-149, 2000. PMID: 10907667

The benzodiazepine receptor (BR) is involved in anxiety. It has been hypothesized that cholinergic projections from the CBF are necessary for modulation of the BR by agonists and inverse agonists. Stowell et al. directly injected 0.18 μg 192-Saporin (Cat #IT- 01) into each hemisphere of the CBF in adult rats. The treated rats had altered responses to external stimuli during an operant conditioned task. These results indicate that the CBF plays an important role in response to fear and anxiety- related stimuli. This system may also mediate the actions of BR ligands.

Intracerebroventricular infusion of CHO5, a rat monoclonal antibody directed against mouse low-affinity nerve growth factor receptor (p75NTR), specifically labels basal forebrain cholinergic neurons in mouse brain.

Rossner S, Schliebs R, Bigl V.

Metab Brain Dis 15(1):17-27, 2000. PMID: 10885538

192-Saporin (Catalog #IT-01) has long been a useful tool for neurobiological research in the rat. For various reasons, many researchers want to perform the same studies in the mouse but have been prevented from doing so by the lack of a suitable antibody against the mouse p75NTR. Rossner et al. describe a rat monoclonal antibody against the mouse p75NTR (Catalog #AB-N02) that demonstrates co-localization of p75NTR and ChAT, and also co-localization of p75NTR and TrkA in the mouse basal forebrain. Internalization and retrograde transport of this antibody in cholinergic basal forebrain neurons is also shown. This evidence indicates that the anti- mouse p75NTR will be effective for use as an immunotoxin.

Chronic Pain Therapeutic

In April of this year ATS applied for funding from National Institute for Mental Health (NIMH) for the toxicology studies of Substance P-Saporin (SP-SAP). This $674,000 supplement to a previous NIMH Small Business Innovative Research grant will cover one of the FDA-required safety and toxicology studies and will bring us closer to clinical trials in humans. On August 14, ATS received notice of the reviewers’ score of these studies. ATS is pleased with the reviewers’ assessment and is optimistic about funding. Collaborating with ATS on this grant are two scientists who are experts in their fields: Dr. Tony Yaksh (UCSD, Dept. of Anesthesiology) who will be heading the toxicology/safety experiments in animals, and Dr. Patrick Mantyh (Univ. Minnesota), who will provide analysis and imaging of tissue samples from the study. Dr. Douglas Lappi (President and Senior Scientist at ATS) is Principal Investigator for this project and plans to begin synthesis of SP-SAP for use in these studies early in October.

The toxicology/safety studies will provide important information about the way SP-SAP may be used to treat intractable pain in humans. First, these experiments should tell us whether SP-SAP has toxic side effects. Second, they should give indications of how safe the drug will be at various doses. Finally, this will be the first time we will study the way the body reacts to the drug: how quickly it is absorbed, how it is broken down in the body, whether any of these breakdown products are toxic, and how quickly the drug and its breakdown products are eliminated from the body. If, after this intensive series of experiments, SP-SAP is determined to be safe to use in humans, ATS will initiate the first clinical trials.

The FDA has advised us that SP-SAP may best be developed as an orphan drug for treatment of pain in patients with terminal cancer. ATS will interact closely with the FDA during the drug development process and will publish updates in our quarterly newsletter and on our website at

NIDA funds ATS research on Galanin

Advanced Targeting Systems (ATS) has just been awarded a $100,000 research grant from the National Institute on Drug Abuse (NIDA). This Phase I SBIR (Small Business Innovation Research) grant proposes to develop a research reagent to study the function of the neuropeptide, galanin. This will be an important tool for scientists to use in the study of galanin’s influence in many biological systems: pain, depression, anxiety, memory and feeding.

Galanin is a 29/30 amino acid peptide and asserts its biological effect through G-protein-coupled receptors that are widely distributed. In the brain, I125-galanin or galanin- analog binding studies show high levels of binding in the cerebral cortex, thalamus, pons, and cerebellum. Outside the brain, the anterior pituitary, pituitary tumors, astrocytes, spinal cord, and gastric and jejunal smooth muscle show ligand binding (1).

At the molecular level, multiple second messenger pathways are activated: inhibition of cyclic AMP, activation of channels including ATP- sensitive K+ channels, inhibition of L-type and N-type calcium channels, stimulation of inositol phospholipid turnover, stimulation and inhibition of calcium mobilization, stimulation of phospholipase A2, activation of MAP kinase, mitogenesis and stimulation of cyclic AMP accumulation (1).

This diversity of biochemical activities leads to a wide array of effects in biological systems. Galanin is reported to modulate feeding and sexual behavior, play a role in pain transmission, affect depression, and may be involved in the pathogenesis of Alzheimer’s disease (2).
For the next six months, ATS will develop and test a galanin-saporin fusion protein to be offered commercially to research scientists worldwide. This targeted toxin will be a valuable research tool to study biological systems and for the study of drug abuse. The presence of galanin receptor-expressing cells in systems that control depression, pain and eating disorders, along with the connection between the opiate receptors, may indicate that galanin plays a role in drug abuse. The removal of these neurons, and their effects on neurons that express opiate receptors, will be a powerful tool to examine the role of galanin in drug use and abuse.

1. Williams RL; Hilton DJ; Pease S; Willson TA; Stewart CL; Gearing DP; Wagner EF; Metcalf D; Nicola NA; Gough NM. Nature 1988, 336, 684-687.

2. Kask K; Berthold M; Bartfai T. Life Sci. 1997, 60 (18), 1523-1533.

Cover Article: CBF Lesioning in Rabbits

Contributed by Dr. Thomas Beach, Sun Health Research Institute, Sun City, AZ

Our hypothesis, developed through our own human and animal studies1-6 and the cell culture work of others (beginning with Nitsch7), is that the normal, age-related loss of cortical cholinergic innervation leads to Aβ deposition and Alzheimer’s disease. To test this hypothesis, we have been using a saporin- conjugated antibody to lesion the cholinergic basal forebrain (CBF) of rabbits. The antibody is the ME20.4 monoclonal8 against the low affinity nerve growth factor receptor, also known as the p75 neurotrophin receptor (p75NTR). This approach had already been shown to result in an effective and specific lesion in rats, but we wished to use an animal with an Aβ sequence identical to that of humans (the rat sequence differs by 3 amino acids), since we considered that, because of this difference, rats may be less likely to produce Aβ deposits. As the IgG192 anti-p75NTR antibody used for rats does not recognize rabbit CBF neurons, we tested the ME20.4 antibody and found, in preliminary immunohistochemical studies, that it stained the rabbit CBF neurons beautifully (Fig 1c,d). We obtained the ME20.4-producing cells from the American Type Culture Collection (ATCC) and forwarded these to Advanced Targeting Systems for antibody production and coupling to saporin.

We injected 30-40 μl of the conjugate into the lateral ventricles of New Zealand white rabbits and sacrificed the animals at 5 weeks, 3 months and 6 months. At all time intervals, we found that lesioned animals showed loss of CBF neurons (Fig 1a-d), cortical ChAT decrements of 50-70%, and profound loss of cholinergic nerve fibers (Fig 1e,f). All lesioned animals showed Aβ deposition in cerebral blood vessel walls and as perivascular diffuse deposits in the neuropil (Figure 1g,h). Biochemical (ELISA) measurements confirmed that Aβ concentrations were elevated in the cerebral cortex, 2.5-fold and 8-fold, respectively, for the forms of the peptide ending in 40 and 42. This model may recapitulate the events leading to Aβ deposition in aging and the sporadic form of Alzheimer’s disease.

[twocol_one][/twocol_one] [twocol_one_last]

Fig 1 Histologic demonstration of the nbm lesion and resultant Aβ deposition.
A,B: rabbit nbm area in control (A) and immunotoxin- treated animals (B), stained for AChE. Note the marked depletion of nbm neurons in the latter.
C,D: rabbit nbm in control (C) and treated (D) animal, stained immunohistochemically for p75 NTR. Note the depletion of neurons in the treated animal.
E,F: frontal cortex from control (E) and treated (F) animals, stained for AChE. Note eradication of cholinergic fibers in the latter.
G,H: Aβ deposition in cerebral cortex of lesioned animals. Aβ is deposited in blood vessel walls (G) and in the perivascular neuropil (H).[/twocol_one_last]


  1. Beach TG and McGeer EG. Acta Neuropathol. 83:292-299, 1992.
  2. Beach TG, Walker, D.G., Cynader MS and Hughes LH. Neurosci. Lett. 142:253-256, 1996.
  3. Beach TG, Hughes LH and Honer, WG. Acta Neuropathol. 93:146-153, 1997.
  4. Beach, TG, Sue, LI, Scott, S and Sparks, DL. Alz. Reports 1:375-380, 1998.
  5. Beach, TG, Potter, PE, Kuo, Y-M, Emmerling, MR, Durham, RA, Webster, SD, Walker, DG, Sue, LI, Scott, S, Layne, KJ and Roher, AE. Neurosci. Lett. 283: 9-12, 2000.
  6. Beach, TG, Kuo, Y-M, Spiegel, K, Emmerling, MR, Sue, LI, Kokjohn, K and Roher, AE. J. Neuropathol. Exp. Neurol. 59:308-313, 2000.
  7. Nitsch, RM, Slack, BE, Wurtman, RJ, and Growdon, JH. Science 258:304-307, 1992.
  8. Fine, A, Hoyle, C, Maclean, CJ, Levatte, TL, Baker, HF and Ridley, RM. Neuroscience 81:331-343, 1997.

Product information related to cover article: ME20.4-SAP, Cat. #IT-15 

SP-SAP as Chronic Pain Therapeutic


SAN DIEGO, CA, NOVEMBER 18, 1999— Chronic, intractable pain afflicts millions of Americans. Pioneering new technology, called molecular neurosurgery and developed by Advanced Targeting Systems, a San Diego-based company, provides the springboard for a one-time injection of a targeted toxin that could result in permanent relief for those suffering constant, unrelenting and crippling pain from cancer and other illnesses. These results are reported in the November 19 issue of the journal Science.

The targeted toxin used in the pain studies is a chemical conjugate composed of the neuropeptide Substance P, and the ribosome-inactivating protein saporin. According to Douglas Lappi, Ph.D., President and Senior Scientist of Advanced Targeting Systems, “Substance P-saporin targets delivery of a toxic compound to those nerve cells that transmit pain messages up the spinal cord to the brain. This precise method allows chronic pain to be permanently stopped without affecting normal pain transmission.”

Substance P-Saporin targets delivery of a toxic compound to eliminate those nerve cells that transmit pain messages (yellow highlight) up the spinal cord to the brain.
This precise method allows chronic pain to be permanently stopped without affecting other neurons (red).
This technology created by San Diego-based Advanced Targeting Systems, creates the spring board for providing a one-time injection of a targeted toxin that could result in permanent relief for those suffering constant pain from cancer and other illnesses.

Dr. Lappi, the inventor of numerous agents and an innovator in the development of targeted toxins, explains, “The scalpel in molecular neurosurgery is saporin, a protein from the seeds of the plant, Saponaria officinalis. Saporin has no way of entering a cell on its own, but when attached to a targeting agent such as an antibody or neuropeptide, it is directed inside the cell and causes cell death. In the case of Substance P-saporin, the saporin is internalized along with Substance P and eliminates those neurons while leaving bystander neurons untouched.”

Dr. Lappi, author of more than 70 scientific publications, devised the idea of studying pain pathways by using the Substance P receptors as a gateway to get inside the target neurons.

Lappi contacted noted University of Minnesota pain expert Dr. Patrick Mantyh to use the material. The current report in Science covers work completed in Mantyh’s laboratory. Mantyh, a pioneer in the use of the molecule in chronic pain research and treatment, first reported on initial results from the use of Substance P-Saporin in a 1997 Science issue.

The targeted toxin on which the research is based centers around an idea first proposed by Ronald G. Wiley, M.D., Ph.D., scientific advisor to Advanced Targeting Systems and clinical neurologist at the Veteran’s Administration Medical Center, Nashville, TN. Advanced Targeting Systems has patents pending for Substance P-Saporin and its uses.

According to the published research in Science, the Substance P-saporin is working well in the laboratory and, according to Lappi, “This means limited clinical trials in humans could begin within two years.”

SFN Poster of the Year 1999

Awarded by ATS at Society for Neuroscience (SFN) Miami, Florida • October 23-28, 1999

474.6 Abolition of cyanide-induced sympathoexcitation by selective lesion of bulbospinal catecholaminergic neurons.
A.M. SCHREIHOFER* and P.G. GUYENET Univ. of Virginia.
Cardiovascular regulation: central control III (POSTER)

The rostral ventrolateral medulla (RVLM) contains BS C1 adrenergic cells and non-CA neurons whose relative importance for the production of sympathetic vasomotor tone and cardiovascular reflexes remains unknown. In the present study we evaluate 2 sympathetic reflexes after selective lesions of BS CA neurons with the neurotoxin saporin-anti-dopamine beta hydroxylase (SAP-DBH). Rats received bilateral microinjections of SAP-DBH (42 ng/200nl/site) into the spinal cord centered at the intermediolateral cell column at T2 & T4 & T6 and were allowed to recover for 3-5 weeks. Arterial pressure (AP), heart rate (HR), and splanchnic nerve activity (SNA) were measured while the rats were chloralose-anesthetized, artificially ventilated, and paralyzed. Baseline AP and HR were comparable between control rats (n-7, 113 +/- 7 mmHg, 426 +/- 12 bpm) and lesioned rats (n=7, 123 +/- 4 mmHg, 448 +/- 7 bpm). In control rats stimulation of the carotid chemoreflex (100 micrograms/kg sodium cyanide, iv) produced a burst in SNA (266 +/- 26%) followed by inhibition (to 18 +/- 3% of base). In contrast, in the SAP-DBH-treated animals cyanide produced only an inhibition of SNA (to 33 +/- 7% of base). Mean AP responses mirrored the SNA responses. In contrast, the Bezold-Jarisch reflex was not diminished in the SAP-DBH-treated rats. Phenyl biguanide (5 micrograms/kg, iv) decreased AP (22 +/- 3 vs. 42 +/- 5 mmHg), SNA (85 +/- 4 vs. 67 +/- 6%), and HR (28 +/- 6 vs. 56 +/- 7 bpm) in control rats and lesioned rats respectively. Histological examination revealed that SAP-DBH depleted the vast majority of BS C1 cells (>70% of the rostral third of the C1 cell group), and >80% of the A5 cell group. These results indicate that sympathetic vasomotor tone persists and rats have a normal mean AP in the absence of most of BS C1 and A5 cells. Although the BS C1 cells may not be required for the Bezold-Jarisch reflex, BS CA cells are essential for the sympathoexcitatory response to cyanide. Work supported by NIH 28785.

Abstracts from Society for Neuroscience (SFN) Symposium October 23-28, 1999 – Miami, Florida

271.1 Inhibition of mustard oil-induced thermal hyperalgesia in an operant escape task by substance P-saporin.

R.G. WILEY*, D.A. LAPPI and C.J. VIERCK Univ. of Florida Brain Inst. and Adv. Targeting Systems, San Diego.

Pain modulation: anatomy and physiology–substance P and NK-1 (POSTER)

272.8 Depletion of IB4-binding sensory neurons results in elevated nociceptive thresholds.

L. VULCHANOVA*, L.S. STONE, T. OLSON, M.S. RIEDL, R. ELDE and C.N. HONDA Univ. of Minnesota, Minneapolis.

Pain modulation: anatomy and physiology–nociceptors (POSTER)

300.15 NGF-mediated alteration of NF-kappa B binding activity after partial immuno-lesions to rat cholinergic basal forebrain neurons.

Z. GU*, T. TOLIVER-KINSKY, J. GLASGOW, L. CHIN and J.R. PEREZ-POLO Univ. of Texas Med. Br., Galveston.

Neurotrophic factors: receptors and cellular mechanisms III (POSTER)

358.5 Lesions of basal forebrain cholinergic neurons eliminate the modulatory effects of benzodiazepine receptor ligands on behavioral and cardiovascular reactions in an anxiogenic paradigm.

J.R. STOWELL*, G.G. BERNTSON and M. SARTER Ohio State Univ.

Cognition: higher functions–lesion/patient studies (POSTER)

474.6 Abolition of cyanide-induced sympathoexcitation by selective lesion of bulbospinal catecholaminergic neurons.

A.M. SCHREIHOFER* and P.G. GUYENET Univ. of Virginia.

Cardiovascular regulation: central control III (POSTER)

554.6 Effects of cortical cholinergic deafferentation upon processing capacity as assessed by an olfactory span task in rats.

M. SARTER*, J. TURCHI and K. GONZALEZ Ohio State Univ.

Learning and memory: pharmacology–acetylcholine I (POSTER)

559.2 Selective cholinergic lesions of the horizontal limb of the diagonal band of Broca affect odor perception in rats.

P. GARCIA, C. LINSTER, M.E. HASSELMO and M.G. BAXTER* Boston Univ. and Harvard Univ.

Learning and memory: systems and functions–cholinergic modulation (POSTER)

559.4 Selective lesions of the nucleus basalis magnocellularis in rats do not affect simple association learning.

A.E. BUTT, T.D. BOWMAN, J.S. NOVOTNEY, J.L. ROGERS, and A. TANABI Department of Psychology, Indiana State University, Terre Haute IN 47809

Learning and memory: systems and functions–cholinergic modulation (POSTER)

559.5 Lack of effect of intraventricular OX7-saporin on working memory in the rat.

C.C. WRENN*, D.A. LAPPI and R.G. WILEY Vanderbilt Univ. and Adv. Targeting Systems, Carlsbad, CA.

Learning and memory: systems and functions–cholinergic modulation (POSTER)

559.6 A developmental role of the cholinergic basal forebrain: behavioural and neurochemical effects of neonatal 192 IgG-saporin lesions.

L. RICCERI*, G. CALAMANDREI and J. BERGER-SWEENEY (SPON: Intl. Behavioural and Neural Genetics Soc.). Inst. Superiore di Sanit‡, Rome and Wellesley Col.

Learning and memory: systems and functions–cholinergic modulation (POSTER)

559.9 GABAergic septohippocampal neurons are not necessary for spatial memory.

A. SECOR, R. NOCERA and K.C.H. PANG* Bowling Green State Univ.

Learning and memory: systems and functions–cholinergic modulation (POSTER)

561.15 Selective immunolesion of substance P receptor expressing interneurons in the hippocampus.

Z. BORHEGYI, R.G. WILEY, D.A. LAPPI, J. MORRELL* and G. BUZSAKI Rutgers Univ., Newark, VA Med. Ctr., Nashville and Adv. Targeting Systems, San Diego.

Limbic system and hypothalamus: electrophysiology II (POSTER)

643.7 Increased susceptibility to flurothyl-induced generalized seizures after immunolesions to cholinergic neurons in the basal forebrain.

D.C. SILVEIRA*, G.L. HOLMES, S.C. SCHACHTER, C. GEULA and D.L. SCHOMER Children’s Hosp. and Beth Israel Deaconess Med. Ctr., Harvard Med. Sch.

Epilepsy: basic mechanisms V (POSTER)

731.2 CTB-saporin induced demyelinating myelopathy in the rat.

G. JANNI*, D.A. LAPPI, P.T. OHARA and L. JASMIN Georgetown Univ., Adv. Targeting Systems, San Diego and UCSF.

Neurotoxicity: exogenous toxins II (POSTER)

754.4 Cholinergic deafferentation of the hippocampus or cortex produces differential modulation of attentional processing.

J.J. WAITE* UCSD and VA Med. Ctr., San Diego.

Neural basis of behavior: cognition–attention: rodent models of attention (POSTER)

803.6 Hippocampal Trk-A receptors are compartmentalized within axonal transport vesicle sites and present in select astrocytes.

M.L. BARKER-GIBB*, S. EINHEBER and T.A. MILNER Weill Med. Col. of Cornell Univ. and NYU Med. Ctr.

Neurotrophic factors: receptors and cellular mechanisms VII (POSTER)

814.2 Molecular Neurosurgery: The Use of Targeted Cytotoxins in Neuroscience.

R. G. WILEY Vanderbilt Univ

Exciting New Advances in Pain Research and Treatment Using Receptor Internalization (SYMPOSIUM)

814.3 Selective Targeting of Pain Regulatory Pathways.

W. J. MARTIN Univ. of California, San Francisco

Exciting New Advances in Pain Research and Treatment Using Receptor Internalization (SYMPOSIUM)

814.5 Receptor Internalization as a Selective Portal of Entry Into Cells.

P. MANTYH Univ. of Minnesota

Exciting New Advances in Pain Research and Treatment Using Receptor Internalization (SYMPOSIUM)

847.3 Cholinergic basal forebrain lesion results in reduced activity of neuronal NO synthase in hippocampal and neocortical areas of the rat brain.

M. HARTLAGE-RUEBSAMEN, W.R. LIPPE* and R. SCHLIEBS Paul Flechsig Inst. for Brain Res., Leipzig, Germany and V. Merrill Bloedel Hearing Res. Ctr., Seattle.

Degenerative disease: Alzheimer’s–neuropharmacology and neurotransmitters I (POSTER)

Society for Neuroscience (SFN) Symposium October 23-28, 1999 – Miami, Florida

Symposium:  “Exciting New Advances in Pain Research and Treatment Using Receptor Internalization Technologies”

D.A. Thomas, NIDA-NIH (co-chair); R.G. Wiley, Vanderbilt University; W.J. Martin, UCSF; M.J. Iadorola, NIDCR-NIH; P. Mantyh, University of Minnesota; R.M. Caudle, University of Florida (co-chair) 

A press conference was held prior to the Thursday, Oct. 28 symposium. Carl Hall, journalist for the San Francisco Chronicle, covered the issues well.

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The theme of the symposium centered on the Advanced Targeting Systems’ technology: targeting specific cell types using receptor internalization. For further details on this technology, check out the ATS tutorial.

Three of the four speakers, Dr. Ron Wiley, Dr. William Martin, and Dr. Pat Mantyh, presented stunning data utilizing products developed by Advanced Targeting Systems. The products covered were: anti-DBH-Saporin, 192-IgG-SAP, OX7-Saporin, Substance P-Saporin, and a conjugate using a more stable analog of Substance P, SSP-Saporin. All of these targeted toxins are currently available from ATS (see targeted toxins, for more information).