- Home
- Knowledge Base
- sfn2001
sfn2001
Destruction by SP-SAP of rat retrotrapezoid nucleus (RTN) neurons expressing the neurokinin 1 receptor (NK1R) decreases breathing at rest and in response to hypercapnia.
Nattie EE, Li A (2001) Destruction by SP-SAP of rat retrotrapezoid nucleus (RTN) neurons expressing the neurokinin 1 receptor (NK1R) decreases breathing at rest and in response to hypercapnia. Neuroscience 2001 Abstracts 573.1. Society for Neuroscience, San Diego, CA.
Summary: Neurons in the RTN are hypothesized to provide both a tonic excitation for breathing and one location for central chemoreception (see Nattie, E., Prog. Neurobiol.1999). Lesions in anesthetized animals support the former while both lesions and focal acidification in unanesthetized animals support the latter. Application of substance P (SP) in the RTN increases respiratory output and immunohistochemistry for the SP (NK1) receptor shows extensive staining in the RTN. To destroy specifically these RTN neurons with NK1Rs we injected unilaterally in the RTN of the rat SP conjugated to the ribosomal toxin, saporin (SP-SAP; 100 nl; 1 uM; Advanced Targeting Systems). We measured ventilation by whole body plethysmography in the unanesthetized rat. At 6 to 15 days following SP-SAP injection, ventilation during air breathing was reduced by 19 to 24% and the response to 7% CO2 inhalation was reduced by 22 to 30%. Subsequent immunohistochemistry showed dramatically reduced NK1R staining in the area of the SP-SAP injection, which is difficult to quantify given the small number of RTN neurons and the extensive NK1R distribution along neuronal processes. RTN neurons with NK1Rs provide both a tonic excitation for breathing and a portion of the response to systemic hypercapnia.
Related Products: SP-SAP (Cat. #IT-07)
Selective immunotoxin lesions of hindbrain norepinephrine/epinephrine (NE/E) neurons impair feeding and corticosterone responses and Fos-immunoreactivity in hypothalamic sites during insulin-induced hypoglycemia (IIH).
Sanders NM, Dinh TT, Pedrow C, Ritter S (2001) Selective immunotoxin lesions of hindbrain norepinephrine/epinephrine (NE/E) neurons impair feeding and corticosterone responses and Fos-immunoreactivity in hypothalamic sites during insulin-induced hypoglycemia (IIH). Neuroscience 2001 Abstracts 635.21. Society for Neuroscience, San Diego, CA.
Summary: Previously,we used the targeted immunotoxin saporin, conjugated to a monoclonal antibody against dopamine Beta-hydroxylase(DSAP),to destroy hypothalamic projecting NE/E neurons. Results showed that NE/E neurons are required for 2-deoxy-D-glucose induced feeding and Fos expression in the hypothalamus. In the present study,we used this same technique to determine if NE/E neurons play a similar role in mediating IIH responses.Rats were injected with DSAP or unconjugated saporin (SAP)into the hypothalamic paraventricular nucleus(PVH).Insulin reduced blood glucose to similar values in DSAP and SAP rats(15 and 17mg/dl, respectively). Glucagon responses to hypoglycemia were unaffected by DSAP,peaking at 597% and 504% of pre-drug levels after insulin in DSAP and SAP rats,respectively.In contrast,the corticosterone response was severely diminished in DSAP rats,peaking at only 123% of pre-insulin levels, compared to 353% in SAP rats.DSAP injections also abolished the feeding response to IIH.DSAP rats ate 0.9g of food during IIH while the SAP rats at 6.1g of food.DBH-ir was abolished in the A1/C1 overlap and reduced in A2,C2,C3 and A6 sites in DSAP rats. In the SAP rats,IIH induced Fos-ir in hindbrain NE/E neurons the PVH, LH and ARC.In DSAP rats, Fos-ir was reduced or abolished in these hypothalamic sites but was preserved in the adrenal medulla.These findings further support the role of hindbrain NE/E neurons in transmitting information from hindbrain glucoreceptive sites to hypothalamic circuits coordinating feeding and neuroendocrine responses to glucose deficit.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Dermorphin-saporin conjugate relieves inflammatory pain after peripheral application.
Palecek J, Paleckova V, Willis WD (2001) Dermorphin-saporin conjugate relieves inflammatory pain after peripheral application. Neuroscience 2001 Abstracts 508.10. Society for Neuroscience, San Diego, CA.
Summary: Opioid receptors have been shown to exist in specific population of DRG neurons signaling nociceptive information from peripheral tissues. In our study, we attempted to selectively destroy these neurons by using a peripheral application of the mu opioid agonist Dermorphin conjugated to ribosome inactivating toxin Saporin (DERM-SAP, Advanced Targeting Systems) in order to alleviate inflammatory pain. Intraarticular or intraplantar injection of carrageenan or CFA was used to induce inflammation in rats. The DERM-SAP conjugate was injected into the inflamed area 12-48h later. Responses of the animals to mechanical and thermal stimuli were tested before and after the inflammation and up to 21 days after the DERM-SAP application. The rats developed heat hyperalgesia in the affected paw 24 hours after the intraarticular CFA injection. In the saline injected group the hyperalgesia persisted for up to 19 days, but in the DERM-SAP injected group the signs of hyperalgesia were improving from day 7. Also mechanical allodynia tested with a VF filament (1.1g) was alleviated in the DERM-SAP group. In the carrageenan group, the DERM-SAP treatment decreased the heat hyperalgesia and prevented the development of hyperalgesia after repeated carrageenan application, 21days after the DERM-SAP treatment. Postmortem evaluation with a specific antibody showed presence of saporin in the DRG neurons. Our results show that peripheral application of DERM-SAP relieves inflammatory pain and suggest that peripheral application of neuropeptides conjugated to cell toxins or other substances such as antisense probes could be a useful tool for treating pain of peripheral origin. Supported by NIH grants NS09743 and NS11253.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
Effects of 192-saporin lesion of the basal forebrain on sleep homeostasis and adenosine receptor (A1) mRNA levels.
Greco MA, Salin-Pascual R, Gerashchenko D, Blanco-Centurion C, Shiromani PJ (2001) Effects of 192-saporin lesion of the basal forebrain on sleep homeostasis and adenosine receptor (A1) mRNA levels. Neuroscience 2001 Abstracts 523.12. Society for Neuroscience, San Diego, CA.
Summary: Adenosine is hypothesized to be a mediator of sleep since adenosine levels in the basal forebrain increase after wakefulness and decrease following sleep. The inhibitory effect of adenosine on wake-active cholinergic neurons is thought to be mediated by the A-1 receptor subtype. We hypothesized that if adenosine inhibition of cholinergic neurons takes place via A-1A receptors on cholinergic neurons, the elimination of cholinergic cells should affect sleep homeostasis. To test this hypothesis, 192-saporin was used to selectively lesion basal forebrain cholinergic cells. 48h baseline sleep was recorded from male Sprague Dawley rats. Subsequently, the rats were kept awake for 12h and 24h recovery sleep was recorded. 192-saporin (4 ug) was then administered ICV. The rats were again continuously recorded for 3 weeks after the injection, a 12h prolonged waking period and during a 24h recovery sleep period. Brain sections processed for visualization of A1 mRNA and/or immunohistochemistry revealed that both ChAT- and parvalbumin-positive cells contained A-1A mRNA. 192-SAP eliminated ChAT immunoreactive cells in the basal forebrain. There were no differences in sleep-wakefulness up to 3 weeks after drug administration, a finding consistent with previous reports. In addition, there were no changes in recovery sleep following prolonged waking in lesioned rats. These results indicate that the cholinergic basal forebrain groups are not the primary mediators of wakefulness or of sleep homeostasis. We suggest that the effects of adenosine are mediated via binding to non-cholinergic neurons.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Basal forebrain cholinergic system: Cortical activation, sleep/waking EEG and evoked potentials.
Shafi R, Berntson GG, Sarter M, Saurer T, Spino M (2001) Basal forebrain cholinergic system: Cortical activation, sleep/waking EEG and evoked potentials. Neuroscience 2001 Abstracts 533.16. Society for Neuroscience, San Diego, CA.
Summary: The role of the basal forebrain cholinergic system in cognitive functions such as arousal, attention and memory has been well documented. The purpose of the present study was to further elucidate the role of the basal forebrain in regulating cortical states and processes that may underlie these functions. Selective lesions of the cholinergic neurons of the basal forebrain were made using the immunotoxin 192 IgG-saporin, which selectively targets the p75 receptor on cholinergic neurons. The effects of these lesions on sleep structure and EEG activity and on afferent priming of cortical reactivity was evaluated. Specifically, we monitored behavioral activity and sleep states and examined the frequency distribution of power distribution in EEG frequency bands during these states. In separate sessions, we also recorded cerebral event-related potentials to auditory stimuli (100 ms, 1 K Hz at 60, 70 and 80 db) after intraperitoneal administration of saline or epinephrine (0.5 mg/kg, which we have previously found to result in priming or enhancement of the auditory evoked response). Compared to controls, lesioned animals showed a reduction in spontaneous activity, reduced power in higher frequency (primarily gamma) EEG bands during both sleep and waking, and altered sleep structure. In addition, lesioned animals displayed lower amplitude auditory evoked potentials and a loss of epinephrine-priming of the evoked response. Results support the view that the basal forebrain cholinergic system may play an important role in cortical activation and the regulation of sleep/waking states, as well as in cortical processing and its enhancement by visceral priming.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic lesions of the thalamic reticular nucleus using 192-IgG-saporin.
Tait DS, Latimer M, Woodson W, Brown VJ (2001) Cholinergic lesions of the thalamic reticular nucleus using 192-IgG-saporin. Neuroscience 2001 Abstracts 313.13. Society for Neuroscience, San Diego, CA.
Summary: The TRN is likely to be involved in attention, based on studies of its anatomy, electrophysiological properties and the effects of lesions (see Guillery et al, 1998, TINS 21:28-32). The cholinergic neurons of the basal forebrain (BF) have also been implicated in attention (Sarter and Bruno, 2000, Neuroscience, 95:933-952). Intriguingly, rostral TRN receives cholinergic innervation from the BF (Hallanger et al, 1987, J Comp Neurol, 262:105-124) and yet the role of acetylcholine in the TRN has not been investigated, in part because of difficulty in selectively manipulating the cholineric input to TRN. 192-IgG-saporin is a conjugation of the ribosome-inactivating protein, saporin, with the monoclonal antibody for the p75 neurotrophin receptor (192-IgG). 192-IgG-saporin, injected into BF or cortical BF-terminal regions, can be used to make selective cholinergic BF lesions. The purpose of the study was to investigate whether it would be possible to lesion the BF cholinergic input to TRN, using the immunotoxin 192-IgG-saporin. Male Lister hooded rats (450-500g) were stereotaxically injected with 192-IgG-saporin into TRN. Doses of 1.4, 1.95 or 2.4μg produced lesions of TRN, with a loss of cholinergic cells observed in the BF at all doses. There was also evidence of depletion of cholinergic input to frontal cortex with all doses. At the highest dose, there was cholinergic depletion in hippocampus. These results suggest that 192-IgG-saporin can be used to lesion the TRN. The behavioural effects of these lesions are under investigation.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Enriched housing, reticular thalamic nucleus and nucleus basalis: Mediators of attention and learning?
Sauro KM, Sweeney M, Saari MJ (2001) Enriched housing, reticular thalamic nucleus and nucleus basalis: Mediators of attention and learning?. Neuroscience 2001 Abstracts 313.14. Society for Neuroscience, San Diego, CA.
Summary: Housing manipulations have been shown to alter behaviour, neural function and morphology. The Reticular Thalamic Nucleus (Rt) may be involved in thalamocortical relay loops possibly acting as a bi-directional filter for sensory information. Similarly, the Nucleus Basalis (NB) may play a role in attention via cholinergic projections to the cortex. In the current experiment 160 female Wistar rats received bilateral lesions of either the Rt (using ibotenic acid), the NB (using 192 IgG-saporin; Advanced Targeting Systems), or both. Following recovery, the rats were allocated to either an enriched or an isolated housing condition for two weeks. Following open field testing, a modification of Tolman’s latent learning paradigm was used to evaluate the effects of the treatments on attention. Thus, prior to behavioural testing half of the rats from each group were pre-exposed to the Spatial Orientation Task (SPOT) while the other half were not. Following sacrifice, brain slices were stained for metabolic activity using the cytochrome-oxidase method, for morphology using cresyl violet stain, and for a marker of cholinergic function, acetylcholinesterase. Data analysis revealed significant interactions among the lesions, housing and latent learning and provided some support for the suggestion that the Rt may filter incoming sensory information whereas the NB may mediate behaviourally relevant attention. Lesions and housing effects were confirmed by histology. (Approved by the Animal Care Committee; supported by Nipissing University).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Visual orienting response and the nucleus basalis of Meynert.
Isaac M, Pearce JM, Muir JL (2001) Visual orienting response and the nucleus basalis of Meynert. Neuroscience 2001 Abstracts 313.2. Society for Neuroscience, San Diego, CA.
Summary: The nucleus basalis of Meynert (nbM), within the basal forebrain, contains a mass of large cholinergic neurones that send axons throughout the cortex. Previous studies have shown the nbM may be involved in attentional processing. The current study attempted to look at the effects of a cholinergic specific nbM lesion (using 192 IgG-saporin) on an attentional task involving two different serial conditioning schedules. In the Consistent condition a light (10s) was followed by a tone (10s), that signaled food. In the Inconsistent condition the light was presented alone for some trials and for other trials the light was followed by the reinforced tone. The orienting response towards the light was measured at three points throughout its presentation: within the first two seconds (light onset) and then twice within the post-onset period (2s-10s). According to the Pearce-Hall theory (1980), animals pay more attention to the light when it is followed by unpredictable events (Inconsistent condition) rather than predictable events (Consistent condition). Accordingly, the orienting response directed towards the post-onset light (2-10s), was stronger for sham operated rats that were trained with the Inconsistent than the Consistent condition. By contrast by the lesioned group was weak and at a similar level for both groups. These results suggest that the nbM lesions prevented enhanced attention to the light in the Inconsistent condition. These findings support the claim that the nbM is important for enhancing attention to stimuli (Chiba et al, 1995).
Related Products: 192-IgG-SAP (Cat. #IT-01)
The effects of cortical cholinergic depletion on the performance of adult rats in an appetitive-to-aversive transfer task.
Schultz JA, Butt AE, George CL, Garraghty PE (2001) The effects of cortical cholinergic depletion on the performance of adult rats in an appetitive-to-aversive transfer task. Neuroscience 2001 Abstracts 313.3. Society for Neuroscience, San Diego, CA.
Summary: The acetylcholinergic (ACh) projections from the nucleus basalis magnocellularis (NBM) to the neocortex have been implicated in attentional processes. In a test of the hypothesis that only complex learning is affected by damage to this cholinergic system, we examined the effects of NBM lesions in an appetitive-to-aversive transfer learning task. Rats were trained using a tone to signal the availability of food reward for lever-pressing before being transferred to an avoidance learning task where the same tone signaled foot-shock that could be escaped or avoided by lever-pressing. A second experiment examined learning in the aversive context only. For both experiments, male Long-Evans rats received bilateral infusions of the immunotoxin192 IgG saporin into the NBM, sham surgery, or no treatment. Acquisition in the appetitive phase of the appetitive-to-aversive transfer task was normal in the NBM lesion group. However, transfer performance in the aversive task was impaired in NBM lesion group; NBM-lesioned rats acquired the avoidance response more slowly and had lower asymptotic avoidance rates than controls. NBM-lesioned rats tested only in the aversive task performed normally. Thus, the deficit in avoidance learning observed in the NBM-lesioned rats previously trained in the appetitive task was not due simply to an inability to learn in the aversive context. Impairments in transfer learning are instead argued to reflect the relative complexity of the appetitive-to-aversive transfer task as compared to either task alone.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Effect of chlordiazepoxide infusions into the basal forebrain on medial prefrontal neural activity of rats during sustained visual attention.
Yurrita MM, Givens B (2001) Effect of chlordiazepoxide infusions into the basal forebrain on medial prefrontal neural activity of rats during sustained visual attention. Neuroscience 2001 Abstracts 313.4. Society for Neuroscience, San Diego, CA.
Summary: There is extensive evidence suggesting a role for the basal forebrain (BF) cholinergic system in attentional processing. In particular, cortical acetylcholine has been shown to modulate performance in a sustained visual attention task, medial prefrontal cortex (mPFC) neural activity, and distractor-related alterations in mPFC neural activity. In order to further characterize the role of the BF in modulation of attention, the effect of direct infusions of the benzodiazepine receptor agonist chlordiazepoxide (CDP) into the BF was investigated. Specifically, this experiment sought to study the effect of two different doses of CDP (20 and 40µg/hemisphere) on mPFC neural activity of rats performing a task that requires them to discriminate between the presence or absence of short, unpredictable stimuli under testing conditions that vary the level of attentional demand. The overall firing rate of mPFC units recorded during performance in the task was not affected by bilateral infusions of either dose of CDP. There was, however, a differential effect of the two doses on the number of units that show an increase in firing rate during the presentation of the distractor. The high dose of CDP increased the percentage of single units that show a distractor-related increase in firing rate, while the low dose had no effect. In order to determine whether the effect of CDP on mPFC neural activity is mediated via cholinergic projections to cortex, the effect of bilateral CDP infusions into the BF on mPFC neural activity will be studied after local cortical deafferentation of the recording area using 192 IgG-saporin. Supported by: NS37026.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Basal forebrain cholinergic and gabaergic neurons mediate different aspects of sustained attention performance in rats.
Sarter M, Burk JA, Graf A, Russell J, Bruno JP (2001) Basal forebrain cholinergic and gabaergic neurons mediate different aspects of sustained attention performance in rats. Neuroscience 2001 Abstracts 313.7. Society for Neuroscience, San Diego, CA.
Summary: Several studies have demonstrated that lesions of basal forebrain (BF) corticopetal cholinergic neurons, produced by infusing the cholinotoxin 192IgG-saporin, impair the ability to detect visual signals in an operant sustained attention task but not to reject nonsignals. Information about the functions of BF non-cholinergic, particularly GABAergic neurons has remained scarce. As infusions of the excitotoxic amino acid ibotenic acid (IBO) are known to predominantly destroy non-cholinergic neurons in the BF, the effects of BF IBO lesions on sustained attention performance were assessed. Rats were trained to perform a sustained attention task and then received bilateral infusions of IBO (0.06 M; 0.5 μL / hemisphere) or of saline (N=8 /group) into the basal forebrain. Postsurgically, rats were trained to stable performance on the sustained attention task. Compared to controls, ibotenic acid-lesioned rats more frequently responded to non-signal events by ‘claiming’ a hit, and they exhibited an increase in hits in response to the briefest signals. Immunohistological analyses confirmed the predominant loss of parvalbumin-positive and thus presumably GABAergic neurons in the BF, while ChAT-positive neurons were partially spared. Likewise, IBO-lesioned animals exhibited an only moderate decrease in cortical AChE-positive fiber density. These and additional findings indicate that BF GABAergic neurons contribute to attentional performance by mediating the animals’ ability to switch between the response-rules for signals and non-signals.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Central origin of ataxic breathing after lesion of preBötzinger complex (preBötc) neurokinin 1 receptor expressing (NK1R+) neurons.
Janczewski WA, Gray PA, Feldman JL (2001) Central origin of ataxic breathing after lesion of preBötzinger complex (preBötc) neurokinin 1 receptor expressing (NK1R+) neurons. Neuroscience 2001 Abstracts 243.2. Society for Neuroscience, San Diego, CA.
Summary: Pathological breathing results from near complete lesions of preBötC NK1R+ neurons in awake adult rats (Gray et al., FASEB J.,15, 2001). To determine whether this ataxic pattern is central in origin, we examined the breathing pattern of rats using combined diaphragmatic EMG (diaEMG) and whole body plethysmography (WBP). Under anesthesia, substance P conjugated to saporin was injected bilaterally into the preBötC (n=7) and EMG electrodes were implanted into the diaphragm (n=10). Up to four days postinjection, all rats breathed normally. DiaEMG postinpiratory activity was evident in all rats and accentuated during brief apnea following spontaneous sighs. After postinjection day 5, injected rats showed a transformation in breathing pattern from normal to ataxic characterized by high frequency breaths of varying amplitude separated by periods of tonic diaphragmatic discharge. There was no lag between the WBP output and diaphragmatic activity (WBP measures virtually paralleled the moving average of diaEMG activity), suggesting the absence of significant flow limitations. During apnea, nonrespiratory movement produced artifacts on WBP signal but did not affect diaEMG. We conclude that ablation of preBötC NK1R+ neurons leads to hypoventilation and apneas of purely central origin without upper airway obstruction or bronchoconstriction.
Related Products: SP-SAP (Cat. #IT-07)
Cholinergic and noncholinergic septal neurons modulate strategy selection in place learning.
Cahill JF, Baxter MG (2001) Cholinergic and noncholinergic septal neurons modulate strategy selection in place learning. Neuroscience 2001 Abstracts 314.14. Society for Neuroscience, San Diego, CA.
Summary: Rats solving a simple spatial discrimination task in a plus-maze initially employ a place learning strategy, then switch to a motor response strategy. The hippocampus is required for the use of a place learning strategy in this task. Rats with 192 IgG-saporin lesions of the medial septum/vertical limb of the diagonal band (MS/VDB), that selectively removed cholinergic neurons projecting to the hippocampus, were significantly facilitated in acquisition of the spatial discrimination, and switched from place to response strategies just as control rats did. Rats with ibotenic acid lesions of the MS/VDB, which produced cell loss in the MS/VDB but little damage to cholinergic neurons, were significantly impaired in acquiring the spatial discrimination and did not reliably employ either a place or response strategy at any point in training. This suggests that the MS/VDB modulates hippocampal involvement in place learning, but that cholinergic MS/VDB neurons are neither necessary nor sufficient for using a place strategy to solve a spatial discrimination.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Environment-spatial conditional learning: Contribution of medial septal cholinergic neurons.
Jackson O, Firoz EF, Janisiewicz AM, Baxter MG (2001) Environment-spatial conditional learning: Contribution of medial septal cholinergic neurons. Neuroscience 2001 Abstracts 314.15. Society for Neuroscience, San Diego, CA.
Summary: Visual-spatial conditional discrimination learning is impaired by damage to the cholinergic septohippocampal neurons in marmoset monkeys (Ridley et al., 1999). We sought to explore the generality of this finding by testing rats with selective lesions of cholinergic septohippocampal projections (made with 192 IgG-saporin) on an environment-spatial conditional discrimination task. In this task, one of two sets of local environmental cues (consisting of a unique geometric shape with unique visual stimuli) directed search to a particular goal location in the environment (selected from eight possible locations). Preliminary observations suggest that rats with selective lesions of medial septal cholinergic neurons are impaired on acquiring this conditional discrimination task, but are unimpaired on acquiring a single discrimination problem using the same cues. This finding is consistent with a general role for septohippocampal cholinergic projections in the learning of conditional discrimination problems, suggesting that medial septal cholinergic neurons subserve cognitive functions other than decremental attentional processing (Baxter et al., 1997, 1999).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Effects of basal forebrain cholinergic lesions on spatial learning in male and female rats.
Rodefer JS, Jonasson Z, Cahill JF, Tobey RE, Baxter MG (2001) Effects of basal forebrain cholinergic lesions on spatial learning in male and female rats. Neuroscience 2001 Abstracts 314.16. Society for Neuroscience, San Diego, CA.
Summary: Studies with a selective toxin for basal forebrain cholinergic neurons have consistently found little spatial learning impairment in rats with lesions limited to basal forebrain cholinergic neurons. However, the basal forebrain cholinergic system is extensively modulated by estrogen and related sex hormones. Furthermore, female mice are more susceptible than male mice to scopolamine-induced impairments in water maze performance (Berger-Sweeney et al., 1995). Hence, behavioral effects of selective cholinergic lesions may differ between male and female rats, a possibility that has not been directly assessed experimentally. In the present study, male and female Long-Evans rats were given injections of 192 IgG-saporin into the medial septum/vertical limb of the diagonal band (MS/VDB), or a control surgery, and postoperatively tested on several spatial learning tasks in the Morris water maze. On place acquisition, female control rats performed worse than male controls; MS/VDB-lesioned rats performed identically to male controls, regardless of sex. Male rats performed better than female rats on reversal of place discrimination, regardless of lesion status. In a test of place learning strategy, cholinergic lesions appeared to enhance the use of a spatial (vs. a motor response strategy) in rats of both sexes. Hence, female rats are not more susceptible to place learning impairment following loss of cholinergic input to the hippocampus; indeed these lesions seem to enhance place learning in female rats. Furthermore, removal of cholinergic input to the hippocampus seems to enhance the selection of a spatial strategy.
Related Products: 192-IgG-SAP (Cat. #IT-01)
A novel method for localized sympathetic nervous system denervation of peripheral tissue using guanethidine.
Bartness TJ, Demas GE (2001) A novel method for localized sympathetic nervous system denervation of peripheral tissue using guanethidine. Neuroscience 2001 Abstracts 309.10. Society for Neuroscience, San Diego, CA.
Summary: A simple technique for the functional deactivation of the sympathetic nervous system innervation of peripheral tissues is described using the local application of guanethidine. Multiple unilateral microinjections of guanethidine were made into one inguinal or epididymal white adipose tissue (IWAT and EWAT) pads of hamsters, whereas the contralateral pad received equivolumetric saline vehicle injections. Guanethidine treatment virtually abolished the sympathetic innervation of both EWAT and IWAT, as measured by the absence of significant norepinephrine (NE) tissue content two weeks later and as suggested by the two-fold increase in IWAT mass characteristic of surgically induced WAT denervation. IWAT and EWAT NE content and mass were unaffected in the contralateral control pads. Guanethidine injections into the spleen also lead to a function sympathectomy as indicated by significant depletions of NE content. Because guanethidine treatment did not decrease body mass nor induce ptosis, no chemical-induced malaise or global sympathetic denervation, respectively, was suggested. We compared the effects of local guanethidine treatment on IWAT NE content and pad mass with the local application of the sympathetic neurotoxin, anti-dopamine beta hydroxylase saporin, and with local surgical IWAT denervation. Guanethidine treatment significantly reduced IWAT NE content to a greater degree than for the alternative sympathectomy methods. These results suggest that locally applied, chemical sympathectomy with guanethidine provides an effective, restricted method for denervating WAT and likely other peripheral tissues.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
192 IgG saporin lesions of the nucleus basalis magnocellularis impair working but not reference memory in a delayed non-match-to-position y-maze task.
Butt AE, Noble MM, Barrett H, Brinegar S, Hixon A, Kester B, Levey D, Rea T, Ryan M, Schulze S, Vogel L (2001) 192 IgG saporin lesions of the nucleus basalis magnocellularis impair working but not reference memory in a delayed non-match-to-position y-maze task. Neuroscience 2001 Abstracts 314.17. Society for Neuroscience, San Diego, CA.
Summary: The current experiment tests the hypothesis that the cortically projecting cholinergic neurons of the nucleus basalis magnocellularis (NBM) are selectively involved in working and not reference memory. Male Long-Evans rats received extensive pre-operative training in a delayed non-match-to-position (DNMTP) task in a Y-maze. In this task, 0-s, 1-min, or 2-min delays were interposed between consistently food-reinforced “sample runs”, where rats were allowed access to only one arm of the maze, and “choice runs”, where rats were allowed access to both arms of the maze but were reinforced only for entering the arm opposite that entered on the previous sample run. Upon completion of pre-operative training, rats were matched for performance and were randomly assigned to a sham lesion group or to the NBM lesion group, which received bilateral infusions of the cholinergic immunotoxin 192 IgG-saporin into the NBM. As predicted, post-operative performance in the NBM lesion group was normal at the 0-s delay but was severely impaired at the 1-min and 2-min delays. Results suggest that the NBM is critically involved in supporting normal spatial working memory but that previously acquired reference memory for the non-matching rule remains intact following selective NBM lesions.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Noradrenergic inputs to the paraventricular nucleus (PVN) is involved in estrogen receptor α expression in the PVN of 48-h fasted and 2DG-injected female rats.
Estacio MA, Tsukamura H, Reyes BA, Maeda KI (2001) Noradrenergic inputs to the paraventricular nucleus (PVN) is involved in estrogen receptor α expression in the PVN of 48-h fasted and 2DG-injected female rats. Neuroscience 2001 Abstracts 409.6. Society for Neuroscience, San Diego, CA.
Summary: Involvement of noradrenergic inputs to the paraventricular nucleus (PVN) in estrogen receptor α (ERα) expression in the PVN during 48-h fasting and 2DG-induced glucoprivation in female rats was determined by examining the effect of destroying the noradrenergic inputs to the PVN using the saporin-conjugated anti-dopamine-β-hydroxylase (anti-DBH-saporin). Ovariectomized rats were injected bilaterally with anti-DBH-saporin in the PVN. After two weeks, animals were either fasted for 48 hours or injected intravenously with 2DG, then perfused with 4% paraformaldehyde. Brain sections were processed for ERα and DBH immunocytochemistry. Forty-eight-hour fasting or 2DG injection siginificantly increased the number of ERα-immunoreactive (ERα-ir) cells in the PVN in control animals. Anti-DBH-saporin injection prevented fasting- or 2DG-induced increase in ERα-ir cells in the PVN. The DBH-ir axons in the parvocellular PVN were severely reduced following anti-DBH-saporin injection in both fasted and 2DG injected rats. Among the brainstem noradrenergic cell groups examined, there was a significant decrease in the number of DBH-ir cells in the A2 region of both fasted and 2DG injected rats treated with anti-DBH-saporin. There was no obvious reduction in the number of DBH-ir cells in the A1 and A6 regions in the anti-DBH-saporin-injected fasted- or 2DG-injected rats. The results suggest that the A2 noradrenergic input to the PVN plays a major role in increasing ERα expression in the PVN in response to 48-h fasting or 2DG-induced glucoprivation.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Dose-dependent effects of intrathecal substance P-saporin and SSP-saporin.
Wiley RG, Kline IV RH, Lappi DA (2001) Dose-dependent effects of intrathecal substance P-saporin and SSP-saporin. Neuroscience 2001 Abstracts 281.11. Society for Neuroscience, San Diego, CA.
Summary: Selective destruction of lamina I dorsal horn neurons expressing the neurokinin-1 receptor (NK-1R) can attenuate responses to capsaicin injection and thermal hyperalgesia/mechanical allodynia in models of inflammatory, persistent or neuropathic pain. In the present study, we sought to determine the relationships between spinal intrathecal dose of substance P-saporin or the related toxin, SSP-saporin, the loss of NK-1R neurons and reduction of phase II formalin responses. Rats were injected intrathecally with 10 ul of either vehicle, 175 ng, 350 ng or 700 ng of SP-sap. Others were injected with either vehicle, 25 ng, 50 ng or 100 ng of SSP-sap. After 2 weeks, nocifensive behavior was scored for 90 min after a unilateral hindpaw injection of dilute formaldehyde. The amount of phase II nocifensive behavior from 20-90 min post injection was totaled for each animal. Rats were sacrificed and transverse lumbosacral spinal cord sections were stained for NK-1R using indirect immunoperoxidase technique. Digital micrographs of the superficial dorsal horn were captured and the number of pixels in the darkest intensity values were expressed as percent of the analysis area for each dorsal horn. Significant correlations were noted for dose vs dark pixel percentage and for dark pixel percentage vs phase II formalin behavior. The greater the toxin dose the greater the loss of NK-1R staining and the greater the attenuation of phase II formalin behavior. These results indicate that the toxin effects on pain behavior are proportional to the degree of loss of lamina I NK-1R expressing neurons.
Related Products: SSP-SAP (Cat. #IT-11)
The role of the cholinergic basal forebrain in learning, memory and reward expectancies.
Savage LM, Buzzette R, Ramirez D (2001) The role of the cholinergic basal forebrain in learning, memory and reward expectancies. Neuroscience 2001 Abstracts 314.18. Society for Neuroscience, San Diego, CA.
Summary: The cholinergic basal forebrain degenerates in Alzheimer’s Disease and the degree of this degeneration correlates with a decline in cognitive processing. In the present study we have modeled this degeneration in the rat by the selective immunotoxin 192 IgG-Saporin. This immunotoxin destroys cholinergic neurons in the basal forebrain nuclei in rats and thus allows for the study of the impact of cholinergic deafferentation on learning, memory, and other cognitive processes without direct effects on other neuronal systems. After intracerebroventricularly infusions of the immunotoxin or vehicle solution, male rats were allowed to recover for three weeks before being tested in a matching-to-position task. The matching-to-position task was altered to influence the type of cognitive strategies a subject would use to solve the task. The main behavioral manipulation was the use of the differential outcome procedure (DOP). The DOP involves correlating each to-be-remembered event with a distinct reward condition. We found that cholinergic lesions did not dramatically impair learning the matching rule. However, the memory performance of subjects with cholinergic lesions was dramatically impaired – if subjects were not trained with the DOP. When subjects were trained with the DOP, and relied on reward expectancies to solve the delayed-matching-to-position task the cholinergic lesion had little effect. These findings demonstrate that cholinergic immunolesions by 192IgG-saporin induce specific cognitive impairments—dependent on task demand characteristics.
Related Products: 192-IgG-SAP (Cat. #IT-01)