sfn2002

Yoder RM, Pang KCH (2002) Effects of gabaergic or cholinergic medial septal lesions on anxiety. Neuroscience 2002 Abstracts 378.1. Society for Neuroscience, Orlando, FL.

Summary: The hippocampus (HPC) is a structure important for spatial learning and memory. GABAergic and cholinergic neurons in the medial septal area (MSA) provide the two major projections to HPC. Complete destruction of HPC or MSA impairs spatial memory. MSA lesions have an anxiolytic effect, and rats with MSA damage appear be more exploratory. Spatial learning and memory may therefore be influenced by anxiety information reaching HPC through MSA. The present study assessed the effects of MSA GABAergic or cholinergic lesions on anxiety in the elevated plus maze and open-field task. Control rats received intraseptal saline; GABAergic lesions were induced by intraseptal domoic acid; cholinergic lesions were induced by intraseptal 192 IgG-saporin. An elevated plus maze was constructed with 2 open arms and 2 closed arms. Following habituation, each rat was placed in the center of the maze, then observed for 5 minutes. Time spent in the open vs. closed arms and number of entries into open vs. closed arms were compared between groups. The open-field task utilized a square arena with center and outer sections delineated on the floor. Following habituation, each rat was placed into the outer section, then observed for 5 minutes, during which the number of line crossings and amount of time spent in center vs. outer sections were calculated for comparison between groups. In both tasks, frequency of freezing, rearing, head dips, stretched-attend posture, grooming, and defecation was also compared between groups. Results of the present study may help elucidate the role of MSA in the effects of anxiety on learning and memory.

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

Wright KM, Yoder RM, Pang KCH (2002) Spatial strategies in rats with cholinergic or GABAergic lesions of the medial septum. Neuroscience 2002 Abstracts 378.2. Society for Neuroscience, Orlando, FL.

Summary: The major projection neurons of the septohippocampal (SH) system are GABAergic and cholinergic. When both populations of neurons are damaged together, deficits in learning and memory occur. However, when only one population is damaged, spatial memory in the water maze and radial arm maze is intact. The present study evaluated whether spatial strategies differed between rats with either GABAergic or cholinergic septal lesions. Domoic acid or 192 IgG saporin (sap) was injected into the medial septum (MS) to damage GABAergic or cholinergic neurons, respectively. Spatial strategies were examined on the plus maze and water maze. In the plus maze, rats were started from a single arm and trained to enter a goal arm containing both the reward and an intra-maze cue. Probe trials assessed whether the rats used place, response or cue strategies. During a probe trial, the starting location and the intra-maze cue were moved from that during training. In the water maze, animals were trained for 9 days in 3-day cycles. The first two days of the cycle used a visible platform and the third day of training was performed with a submerged platform. A single probe trial was conducted on day 10. On the probe trial, the first quadrant visited determined whether rats were using cue, place, or response strategies. Preliminary results show that rats treated with domoic acid use the place strategy on all probe trials in the plus maze, but do not use a consistent strategy in the water maze. Sap-treated animals also use mainly a place strategy. The results of this study may help determine the role of MS neurons in spatial strategy selection.

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

Butt AE, Hamilton DA, Duerkop MS, King DD, Gibbs RB, Sutherland RJ (2002) Spatial memory impairments in rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis. Neuroscience 2002 Abstracts 378.5. Society for Neuroscience, Orlando, FL.

Summary: In three experiments we test the hypothesis that the nucleus basalis magnocellularis (NBM) is involved in spatial learning and memory. Rats received 192 IgG-saporin lesions of the NBM or sham surgeries prior to testing in the Morris water maze task. In Exp. 1, rats were trained to find a hidden platform, receiving 4 trials per day. In Exp. 2, rats were trained with the hidden platform located in one position on the first 3 trials and in a second position on the 4th trial each day. In Exp. 3, rats were trained in a novel environment with the hidden platform located in a new position every 2 days. In Exp. 1, the NBM lesion group showed longer mean latencies to locate the platform than controls on the first several days of testing. Group differences were greatest on the earlier trials within the 4-trial blocks, with performance in the NBM lesion group recovering to control levels on later trials. In Exp. 2, performance in the NBM lesion group was again impaired, with greater group differences occurring on earlier trials within the 4-trial blocks. In Exp. 3, performance during the first block of trials for the different platform locations did not differ between groups, whereas performance on the 1st trial within the second block of trials was impaired in the NBM lesion group. Analysis of AChE staining and assay of ChAT activity confirm the selectivity of the lesions to the cortically-projecting neurons of the NBM and the sparing of cholinergic medial septal projections to hippocampus. Data suggest that NBM lesions interfere with consolidation of memory for spatial locations.

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

Janisiewicz AM, Rodefer JS, Baxter MG (2002) Visual-spatial conditional discrimination learning in rats with lesions of cholinergic medial septal/diagonal band neurons. Neuroscience 2002 Abstracts 378.6. Society for Neuroscience, Orlando, FL.

Summary: Loss of cholinergic neurons in the medial septum/vertical limb of the diagonal band (MS/VDB) seems to impair visual-spatial conditional learning tasks, in which the location of a correct spatial response is signaled by a visual cue. We examined visual-spatial conditional learning in several automated touchscreen tasks in male Long-Evans rats with selective lesions of MS/VDB cholinergic neurons produced by 192 IgG-saporin. One group of rats was first trained on a simple visual discrimination followed by two visual-spatial conditional tasks. In the first conditional task the rat responded to the left or right member of a pair of identical visual stimuli depending on which stimulus pair was displayed. In the second conditional task one of two centrally-displayed stimuli directed the rat to respond to an illuminated panel on the left or right, depending on which visual stimulus was displayed centrally. MS/VDB-lesioned rats were unimpaired on the simple visual discrimination and the first conditional task, but were severely impaired relative to controls on the second conditional task. However, in a second group of rats trained only on the second conditional task, MS/VDB-lesioned rats were superior to controls, who performed poorly. The different results between the two cohorts appear to reflect transfer effects present in the control rats that are absent in the MS/VDB-lesioned rats. These findings suggest that conditional learning deficits following MS/VDB cholinergic lesions may depend on the particular strategy used to solve the conditional task, which may in turn be influenced by the animal’s testing history.

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

Frick KM, Kim JJ, Baxter MG (2002) Effect of 192-IgG saporin lesions of the entire basal forebrain on emotional and spatial learning. Neuroscience 2002 Abstracts 379.1. Society for Neuroscience, Orlando, FL.

Summary: Scopolamine administration studies suggest that acetylcholine appears to be important for acquisition of contextual fear conditioning (FC), but its involvement in consolidation of fear remains a matter of debate. We examined the role of the basal forebrain cholinergic system in emotional learning and memory by testing male Sprague-Dawley rats with 192 IgG-saporin lesions of basal forebrain cholinergic neurons in contextual and tone FC. Lesions were made either 7 days before (n=10) or one day after (n=10) FC and targeted all basal forebrain nuclei; sham-operated rats (n=5 per condition) served as a comparison. Spatial learning in a one-day water maze task provided a comparison for effects of the lesions on FC. Pretraining lesions had no effect on freezing to tone or context. Posttraining lesions produced a mild impairment in freezing to context, but had no effect on freezing to tone. Both groups were impaired in production of 22 kHz ultrasonic vocalization (USV) associated with fear. Performance on water maze training trials was surprisingly impaired in lesioned rats, although this impairment did not interact with training block and probe trial performance was unimpaired, suggesting that it did not reflect a learning impairment. Radioenzymatic assays of choline acetyltransferase activity in neocortex and hippocampus revealed substantial (>80%) decreases in cholinergic input. These data suggest that conditioned fear-induced USV is more sensitive to the loss of basal forebrain cholinergic neurons than conditioned fear-induced freezing.

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

Nattie EE, Li A, Richerson G, Lappi D (2002) Specific killing of rat medullary raphe 5-HT neurons by a serotonin transporter antibody-saporin conjugate reduces the ventilatory response to increased CO2 during sleep and wakefulness. Neuroscience 2002 Abstracts 221.3. Society for Neuroscience, Orlando, FL.

Summary: CO2 increases the firing rate of medullary raphe 5-HT neurons in vitro (Richerson et al., Respir. Physiol. 129: 175-190, 2001) and focal CO2 dialysis in the medullary raphe increases ventilation in the sleeping rat (Nattie and Li, J. Appl. Physiol. 90: 1247-1257, 2001). To examine in vivo the relative importance of these 5-HT neurons in chemoreception we used an antibody to the external ring of the serotonin tranport protein (SERT)(SFN abstract #814.9, 2001) conjugated to the cell toxin saporin (SAP). Rat medullary raphe neurons (P0) in culture assayed by TPOH immunoreactivity were killed by 10 and 5 nM SERT-SAP with peak effects at 4 and 7 days, respectively. Non-serotonergic neurons were unaffected. In adult rats after measurement of baseline ventilatory values, we placed EEG/EMG electrodes and injected the SERT-SAP conjugate (1 uM) into the medullary raphe (two adjacent 100 nl injections). There was substantial loss of TPOH but not NK1R immunoreactivity measured at 14 days. There was no effect on ventilation during air breathing awake or asleep. Ventilation during 7% CO2 was significantly decreased in sleep (P < 0.001; repeated measures ANOVA) at days 1, 3, 7, and 14 (-13 to -15%; P < 0.05; Tukey post-hoc test) and in wakefulness (P < 0.01; repeated measures ANOVA) at days 1, 3, 7, and 14 (-10 to -16%; P < 0.05; Tukey post-hoc test). Medullary raphe serotonergic neurons in the rat play an important role in the ventilatory response to systemic hypercapnia during sleep and wakefulness.

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

Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA (2002) Lack of capsaicin (CAP)-evoked sensitization following SP-SAP treatment is not attributed to decreased CAP-evoked exciataion. Neuroscience 2002 Abstracts 351.24. Society for Neuroscience, Orlando, FL.

Summary: The depletion of SPR+ neurons in the spinal cord by substance P-saporin conjugate (SP-SAP) prevents the development of central sensitization, induced by capsaicin (CAP). SP-SAP treatment causes a dramatic decrease in CAP-evoked excitation of remaining nociceptive neurons. The lack of central sensitization after SP-SAP may be due to the decreased excitation of these neurons by CAP. We therefore compared excitation and sensitization following intraplantar injection of different doses of CAP (10 and 100 μg) in rats pretreated intrathecally with vehicle (VEH) or SP-SAP. Injection of 10μg or 100 μg CAP evoked activation and sensitization of nociceptive neurons in VEH-treated rats. Mean responses to von Frey stimuli doubled and heat threshold decreased by about 6˚ C. In SP-SAP rats, 10 μg CAP evoked excitation that was <60% of control whereas 100 μg CAP evoked excitation that was similar to control values. However, sensitization failed to occur following either dose of CAP. In addition, we examined whether effects of SP-SAP was mediated by descending modulation. Transsection of the dorsolateral funiculus increased spontaneous activity of nociceptive neurons in rats pretreated with VEH, but not with SP-SAP. Our data show that the development of central sensitization is dependent on neurons that possess the SPR, and that these neurons appear to be part of a supraspinal loop that modulates descending tonic inhibition.

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

Bradley QR, Borowski TB, de Lacalle S (2002) The effects of 17ß-estradiol on odor discrimination of ovariectomized and intact young and aged rats following unilateral lesions of the nucleus of the horizontal diagonal band of broca (HDB). Neuroscience 2002 Abstracts 385.3. Society for Neuroscience, Orlando, FL.

Summary: Estradiol exerts beneficial effects on cognitive performance. The present study was designed to investigate the effect of estradiol on learning and memory following the destruction of cholinergic neurons of the HDB, a basal forebrain region that exhibits significant neuronal loss during aging and may underlie the cognitive deficits associated with Alzheimers disease. Young (3 months old) and aged (20 months old) ovariectomized and gonadally intact Fisher 344 female rats were given unilateral lesions of the HDB with the cholinergic immunotoxin 192 IgG-saporin (.075mg/ml). Starting one week after surgery rats were tested on an odor discrimination task whereby rats were trained to associate a food reward buried within a scented cup of sand relative to a dissimilar scented cup of sand that contained no reward. Following stable levels of acquisition and retention, subjects were exposed to a reversal procedure where the previously unrewarded cup was now baited. Odor discrimination acquisition, retention and reversal were assessed before and after one month of 17β-estradiol exposure or placebo. Analysis of learning curves revealed that young rats performed better than the aged animals independent of estradiol treatment during the reversal component of the task. However, within each age group 17β-estradiol treatment facilitated performance in ovariectomized rats relative to placebo controls. These findings shed new light on the cognitive enhancing properties of estradiol in age-related cholinergic neurodegenerative disorders.

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

Sheriff ST, Xiao C, Chance WT, Kasckow JW, Balasubramaniam A (2002) Selective lesion of neuropeptide Y (NPY)-receptor neurons in hypothalamus inhibit food intake and reduces body weight in rats. Neuroscience 2002 Abstracts 384.1. Society for Neuroscience, Orlando, FL.

Summary: Administration of NPY into hypothalamic areas elicits a most powerful feeding response in rats. The neuronal cell type mediating this orexigenic signal is not clearly understood. To determine the role of NPY-responsive neurons in feeding behavior, we selectively lesioned NPY-receptor neurons by using avidinylated saporin (Av-Sap) mixed with biotinylated NPY. Av-Sap-Biotin NPY complex (ASBN 2.5ug/5ul CSF) or saporin (2ug/4ul CSF) was injected into intracerebroventricle (ICV) of Sprague Dawley rats. Food intake (FI) and body weight was monitored for seven days. On the eighth day NPY (1ug/1ul CSF) was injected into ICV and the FI was monitored for four hours. Injection of ASBN showed a severe reduction in food intake (54%) on the seventh day in comparison to saporin-treated group. ASBN-treated group showed a decrease in the body weight by 24%. The Saporin-treated group showed little body weight reduction (4%). NPY-induced food intake was also reduced in ASBN-treated group. Immunohistochemical analysis revealed a moderate reduction of Y1 receptor (Y1R) neurons in the PVN and arcuate nucleus in this group. Loss of tyrosine hydroxylase neurons in the arcuate nucleus was observed in ASBN-treated group. These results suggest that NPY-receptor neurons may be essential for maintaining the energy homeostasis.

Related Products: Avidinylated-SAP (Cat. #IT-09)

Hodges MR, Forster HV, Wenninger JM, Brozoski DT, Leekley T, Klum L, Feroah TR, Pan LG, Sengupta J (2002) Effects of lesions in the medullary raphe nucleus on sleep and breathing in adult goats. Neuroscience 2002 Abstracts 321.8. Society for Neuroscience, Orlando, FL.

Summary: The medullary raphe nucleus (MRN) contains populations of both neurokinin-1 and glutamate receptor positive neurons (NK1R+, GluR+). The MRN is also thought to influence breathing during wakefulness and sleep. Therefore, to test the MRN influence on breathing during sleep, adult goats (n=4) were chronically instrumented with microtubules into the MRN and allowed >3 weeks to recover. Sleep was monitored during a period of 6 hours (9pm-3am) prior to and 6-8 days after injection of saporin-substance P (SAP-SP), and the night of and 10-14 days after injection of ibotenic acid (IA). During sleep, EEG, EOG, diaphragm EMG, heart rate and blood pressure were monitored, and arterial blood was sampled. We found no significant effect of neurotoxic lesions on relative percentages of time spent in NREM and REM sleep compared to the post-implant control studies. We also found no evidence of ataxic breathing patterns during awake, NREM or REM states after injection of SAP-SP or IA into the MRN. However, evidence of central apnea was present in 3 of 4 goats. The apneustic events were most frequent during NREM, and less frequent or absent during wakefulness and REM sleep. These apneas were 6-20 seconds in duration and resulted in marked variations in PCO2 and PO2. There was also a tendency for hyperventilation during sleep after IA injections. We conclude that lesions in the MRN by loss of NK1R+ and GluR+ neurons can affect breathing during sleep without affecting sleep itself.

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