sfn2001

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)

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)

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)

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)

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)

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)

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)

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)

Bailey AM, Rudisill ML, Hoof EM, Loving ML (2001) The effects of 192 IgG-saporin lesions to the nucleus basalis magnocellularis/substantia innominata (nBM/SI) on two learning set formation tasks and open field activity. Neuroscience 2001 Abstracts 85.13. Society for Neuroscience, San Diego, CA.

Summary: Male Long Evans rats (Rattus norvegicus) were used to investigate the role of the nucleus basalis magnocellularis/substantia innominata (nBM/SI) in learning set formation. Rats with bilateral 192 IgG-Saporin lesions to the nBM/SI were tested on olfactory discrimination learning set, discrimination reversal learning set, and open field activity. Assessment of open field activity indicated no group differences in general activity levels. Control animals performed significantly better than chance on trial 2 across the 50 problems given in the olfactory discrimination learning set paradigm, suggesting evidence of learning set formation. The nBM/SI lesion group did not perform significantly above chance on trial 2 overall; however, they did perform above chance on trial 2 over the last 10 problems in the olfactory discrimination learning set task. Discrimination reversal followed testing on the olfactory discrimination learning set task. No group differences were seen in discrimination reversal performance. Both control and nBM/SI lesioned animals performed well on the discrimination reversal learning set task, improving with each reversal, and both groups performed significantly higher than expected by chance on trial 2 in the discrimination reversal paradigm, indicating learning set formation. Results suggest that removal of the nBM/SI cholinergic system through 192 IgG-Saporin lesions impairs early acquisition of learning set compared to control animals, but does not interrupt later use of learning set formation.

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

Stahl CE, Kusayama T, Keep M, Elmer E, Watanabe S, Borlongan CV (2001) Cyclosporine-A improves performance in passive avoidance task in adult rats with basal forebrain lesions. Neuroscience 2001 Abstracts 101.11. Society for Neuroscience, San Diego, CA.

Summary: While mainly used as an immunosuppressant, newly identified properties of CsA suggest its potential as a therapeutic agent for neurological disorders. In the present study, we investigated the effects of CsA in acquisition and retention of passive avoidance task in adult rats lesioned with 192-IgG-saporin, an immunotoxin that targets cholinergic neurons in the basal forebrain. Starting on the day of the lesion up to 7 days thereafter, animals received either daily CsA (10 mg/kg, i.p. ) or vehicle alone. On day 8 (acquisition), animals were trained in a three-compartment shuttle box passive avoidance task. Twenty-fours later, the retention tests were performed. During the acquisition phase, animals that received CsA treatment significantly entered less in the shock-associated box than those that received vehicle alone. However, the mean total acquisition times between the two groups were not statistically significant. In the retention phase, CsA-treated animals displayed significantly longer latency to stay in the safe compartment compared to vehicle-treated animals. Histological analysis using ChAT immunostaining revealed sparing (80% of control) of basal forebrain cholinergic neurons in CsA-treated animals. The use of CsA may prove beneficial for treatment of neurological disorders characterized by a dysfunctional cholinergic system.

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