sfn2004

Ritter S, Flynn FW, Dinh TT (2004) Immunotoxic destruction of hindbrain catecholamine neurons impairs the vasopressin response to hypovolemia. Neuroscience 2004 Abstracts 660.4. Society for Neuroscience, San Diego, CA.

Summary: In order to better understand the involvement of hindbrain catecholamine neurons in hypovolemia-induced vasopressin secretion, we lesioned these neurons selectively using anti-dopamine beta-hydroxylase (dbh) conjugated to the ribosomal toxin, saporin (DSAP). When injected into catecholamine terminal sites, this neurotoxin is selectively internalized by and retrogradely transported in dbh-containing neurons, destroying cell bodies that innervate the injection site. We microinjected DSAP or unconjugated saporin (SAP) control bilaterally into the medial hypothalamus of female rats to destroy catecholamine neurons innervating the magnocellular areas of the paraventricular nucleus (PVH). The lesion was verified at the conclusion of the experiment by analysis of dbh-immunoreactive terminals in the PVH and cell bodies in hindbrain catecholamine cell groups. Two weeks after DSAP injection, hypovolemia was induced by remote withdrawal of blood (1 ml/min for 4.5 min) using a chronically implanted intra-atrial catheter. Blood was sampled between 0-2 and 2-4.5 min and at 20 and 50 min after the start of blood withdrawal. Plasma vasopressin was extracted and analyzed using ELISA. The DSAP lesion severely impaired the vasopressin response. Responses at 20 min were 35 pg/ml in the SAP control and 21 pg/ml in the DSAP rats. Responses at 50 min were 45 pg/ml in the SAP and 23 pg/ml in the DSAP lesioned rats. Results indicate that hindbrain catecholamine neurons play a crucial role in full expression of the vasopressin response to hypovolemia.

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

Xu F, Zhuang J, Hernandez J, Shi S (2004) Apnea induced by stimulation of bronchopulmonary C-fibers (PCFs) depends on neurons expressing the neurokinin a receptor (NK1R) in the commissural subnucleus of the nucleus tractus solitarius (cNTS). Neuroscience 2004 Abstracts 661.13. Society for Neuroscience, San Diego, CA.

Summary: Stimulation of PCFs by right atrial injection of capsaicin (CAP) reflexly produces an apnea and hypotension via stimulating cNTS neurons. Recent evidence indicates that activation of NK1R within the cNTS significantly amplifies this apneic response (Mutoh, et al., Am J Physiol, 2000). We asked whether the cNTS contained the highest density of the neurons responding to PCF stimulation and expressing NK1R, and what the effect of selective destruction of these neurons was on the cardiorespiratory responses to CAP. In the first series of our experiments, double labeling (c-fos and NK1R immunoreactivity) was used to mark the medullary neurons that were activated by right atrial injection of CAP (0.5-1.0 µg) and displayed NK1R. We found that compared to control (vehicle injection), the greatest enhancement of and highest density of Fos expression were observed within the cNTS, and a number of Fos-stained cNTS neurons had expression of NK1R. In the second series of our experiments, bilateral microinjection (100 nl) of substance P-saporin conjugate (SP-SAP) to selectively destroy the local neurons containing NK1R and SAP (control) into the cNTS was performed in two groups of rats, respectively. Our results showed that at 18 days after SP-SAP (rather than SAP) injection, the majority of cNTS NK1R neurons were destroyed. This lesion did not significantly change cardiorespiratory baseline variables, but did eliminate the apnea and reduce the hypotension induced by CAP. In sharp contrast, the lesion failed to affect the cardiorespiratory responses to hypoxia (10% O2 for 1 min). These findings strongly suggest that cNTS neurons with NK1R are necessary for the PCF-mediated cardiorespiratory responses but are not significantly involved in the cardiorespiratory response to acute hypoxia.

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

Conner JM, Chiba AA, Tuszynski MH (2004) The basal forebrain cholinergic system is essential for cortical plasticity and functional recovery following brain injury. Neuroscience 2004 Abstracts 685.12. Society for Neuroscience, San Diego, CA.

Summary: Localized damage to the motor cortex typically results in impaired motor function. Functional recovery following focal brain injury presumably requires the reorganization of cortical circuitry, enabling undamaged areas remote from the lesion site to take over function. Neuronal mechanisms mediating plasticity of cortical representations are not fully understood, but recent studies have indicated that the basal forebrain cholinergic system may play an essential role. In the present study, we investigated the hypothesis that the basal forebrain cholinergic system is essential for enabling cortical reorganization required for functional recovery following focal motor cortex lesions. Following focal cortical injury, performance in a previously learned skilled reaching task dropped by ~75%. After 5-weeks of rehabilitative training, normal (cholinergically-intact) rats recovered 55.2 ± 4.4% of their pre-lesion reaching performance. Rats with specific lesions of the cholinergic neurons projecting to the cortex showed only 18.1 ± 7.7% recovery (p<0.002). Intracortical mapping revealed that massive reorganization of motor representations had occurred in the cortex following focal cortical injury and rehabilitative training. A significant 48.6 ± 12.2% increase (p=0.001) in the size of the rostral forelimb area (RFA) was seen in cholinergically-intact, functionally recovered, rats. In contrast, the size of the RFA did not change in cholinergic-lesioned animals. Subsequent ablation of the RFA completely disrupted skilled reaching performance, suggesting the RFA was essential to the recovered function. These results demonstrate that functional recovery following discrete cortical injury requires basal forebrain cholinergic mechanisms and suggest that the basis for this recovery is the cholinergic-dependent reorganization of motor representations.

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

Tait DS, Brown VJ (2004) Cell-body lesions of basal forebrain impair reversal learning but not attentional set-shifting in rats. Neuroscience 2004 Abstracts 779.12. Society for Neuroscience, San Diego, CA.

Summary: There is considerable evidence for a role of basal forebrain acetylcholine in a wide range of attentional tasks (see Sarter & Bruno, 2000, Neurosci, 95:933-952), but previous work from this laboratory found that basal forebrain cholinergic projections are not critical for the acquisition, maintenance and shifting of attentional set (Tait et al, 2002 SfN abstr 286.2). As GABAergic basal forebrain projections to cortex may be important for “cognitive flexibility” (Sarter & Bruno, 2002, Eur J Nsci, 15:1867-1873), the present study assessed the effects of non-specific basal forebrain lesions. Male Lister hooded rats received infusions of 200nl 0.06M ibotenic acid into basal forebrain, at coordinates: nosebar –3.3; AP –0.9; ML ±2.9; DV –6.9. We used the rat attentional-set shifting task (Birrell & Brown, 2000, JNsci, 20:4320-4324), in which rats forage in digging bowls for food rewards, to assess discrimination learning (based on the odor of the bowls or the medium in which the food was hidden), reversal learning and attentional-set shifting (when the relevant aspect of the stimulus is switched; for example, a rat previously attending to odor, now must attend to digging medium or vice versa). There was no impairment in discrimination acquisition or in shifting of attentional-set. Lesioned rats were impaired only on the first of three discrimination reversals, taking significantly longer to reach criterion than controls. Prior evidence indicating no effect of selective BF cholinergic depletion via 192-IgG-saporin administration on reversal performance (Tait et al, 2002) leads us to conclude that the non-cholinergic neurons – most likely the GABAergic projection to prefrontal cortex and thalamus – have an important role in reversal learning. These data are strikingly similar to the effects of excitotoxic basal forebrain lesions in monkeys (Roberts et al, 1992, NSci, 472:251-264).

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

Cordova CA, Yu AJ, Chiba AA (2004) Attention, uncertainty, and acetylcholine: Effects of nucleus basalis cholinergic lesions on probabilistic inference. Neuroscience 2004 Abstracts 779.13. Society for Neuroscience, San Diego, CA.

Summary: Animal investigations suggest that the basal forebrain corticopetal cholinergic system helps to regulate attention to unpredictable events. In light of these findings, computational theorists propose that cholinergic neurons precisely alter the way that sensory stimuli are processed in the cortex in light of how well predicted they are. In an initial test of this theory, two groups of rats were trained to respond to probabilistic stimuli presented serially in one of four spatial locations with varying degrees of predictive uncertainty (arising from a 2-layer Hidden Markov model). Following training, one group of rats was given a selective cholinergic lesion of the nucleus basalis/substantia innominata region of the basal forebrain using 192-IgG Saporin. The lesioned rats were unable to allocate attention appropriately, as evidenced by the decreased accuracy of responses to less probable stimuli. These findings provide support for the notion that the basal forebrain corticoptetal cholinergic system facilitates attention by regulating the balance of learned expectations and sensory processing during stimulus inference.

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

Corley SR, Atkinson M, Cabrera S, Castillo A, Crawford D, Kitto M, Butt AE (2004) Cholinergic basal forebrain lesions disrupt acquisition of cued and uncued differential reinforcement of low rate responding. Neuroscience 2004 Abstracts 436.10. Society for Neuroscience, San Diego, CA.

Summary: The frontal cortex, medial septum/vertical diagonal band (MS/VDB), and hippocampus have been implicated in supporting differential reinforcement of low rate responding (DRL) behavior in rats. Because the frontal cortex and hippocampus receive cholinergic input from the basal forebrain, we hypothesized that 192 IgG-saporin (SAP) lesions of the basal forebrain would disrupt DRL acquisition in the current experiment. To distinguish between potential deficits in timing, as opposed to impairments in response inhibition, we trained rats in either the standard DRL task (which requires both timing of behavior and response inhibition) and on a cued version of the task (which does not require the ability to time behavior but does require response inhibition). Rats were first shaped to bar press before receiving either bilateral SAP lesions of the basal forebrain or sham lesions. Rats were returned to bar press training for 5 more days. Rats were then shifted to a DRL 20 s, LH 10 s (limited-hold 10 s) schedule of reinforcement. Half of the rats were provided with a cue light signaling the availability of reinforcement, whereas the other half underwent standard DRL 20 s LH 10 s testing without the visual cue. Rats with basal forebrain lesions showed a transient impairment in response inhibition in both the standard and the cued version of the DRL task. Both lesion groups made more responses at short inter-response-intervals than controls across the first 15 test days, although this impairment attenuated by the 20th test day. These data suggest that the cholinergic basal forebrain is involved in learning to withhold responding during acquisition in DRL.

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

Arshad S, Li P, Fitz NF, Johnson DA (2004) Effect of dehydroepiandrosterone sulfate on retention in passive avoidance in septal hippocampal cholinergic lesioned rats. Neuroscience 2004 Abstracts 436.11. Society for Neuroscience, San Diego, CA.

Summary: Infusions of 192 IgG-saporin (SAP) into the medial septum (MS) selectively destroys cholinergic neurons projecting to the hippocampus. Our previous study demonstrated that this lesion impairs retention but not acquisition of a passive avoidance (PA) task in rats. The present study determined whether the neurosteroid Dehydroepiandrosterone sulfate (DHEAS) (0, 1, 3, 10, 30 mg/ml) could reverse SAP induced impairments of PA retention. Male Sprague-Dawley rats were administered either SAP (.22μg/μl) or vehicle directly into the MS. Passive Avoidance training began 2 weeks later. Training consisted of placing the animal into the lighted chamber of the apparatus and then delivering a foot shock (.75mA, 1 sec), when the animal moved into the adjacent darkened chamber. Training was repeated until the animal avoided the dark chamber for 2 consecutive trials of 2 minutes duration. Retention (latency to crossover to the dark chamber) was tested after seven days. DHEAS was administered one hour prior to retention testing. Results showed a dose dependent increase in crossover latency in SAP treated animals. DHEAS treatment in control animals, however, resulted in a dose dependent decrease in crossover latency. Thus, DHEAS attenuated the impairment in retention in SAP treated animals with hippocampal cholinergic hypofunction, but impaired retention in cholinergically intact rats in PA.

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

Fitz NF, Li P, Johnson DA (2004) Effects of dehydroepiandrosterone sulfate on delayed match to position T-maze task performance in 192- IgG saporin lesioned rats. Neuroscience 2004 Abstracts 436.2. Society for Neuroscience, San Diego, CA.

Summary: Prior studies have shown that infusion of 192 IgG-saporin (SAP), a cholinergic neurotoxin, into the media septum (MS) of rats selectively lesions cholinergic neurons that project to the hippocampus, resulting in impaired acquisition of a delayed matching to position (DMP) T-maze task. Since the neurosteriod dehydroepiandrosterone sulfate (DHEAS), displayed memory enhancing properties in rodents, the present study investigated the effects of DHEAS administration on MS SAP lesioned animals. Male Sprague-Dawley rats received intraseptal infusions of either cerebrospinal fluid or SAP (0.22 μg/μl). Fourteen days later, the rats were administered IP injections of either DHEAS (20mg/ml) or vehicle one hour prior to DMP testing. During the acquisition phase of testing, each rat completed 8 trial pairs per day until reaching criterion (15 of 16 correct choices). Treatment with DHEAS resulted in a 10% shortening of the number of days to reach criterion in the SAP treated animals compared to SAP non-treated animals.

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

Fletcher BR, Guzowski JF, Baxter MG, Shapiro ML, Rapp PR (2004) Hippocampal Arc and Homer 1a expression in behaviorally characterized 192 IgG-saporin lesioned rats. Neuroscience 2004 Abstracts 436.4. Society for Neuroscience, San Diego, CA.

Summary: Fornix lesions impair hippocampal dependent learning and block behavioral induction of the immediate-early gene Arc. The present experiment tested the role of cholinergic innervation in the transcriptional induction of the activity related immediate-early genes Arc and Homer 1a. 192 IgG-saporin or vehicle was injected into the medial septal nucleus and vertical diagonal band. Behavioral characterization on cued and spatial delayed match-to-place tasks in a radial arm water maze revealed an impairment in cognitive flexibility, but not spatial memory in lesioned animals. Immediately after animals explored two novel environments their brains were processed for fluorescence in situ hybridization with probes for Arc and Homer 1a to reveal the recent activation history of individual neurons. Confocal stereological quantification of labeling in the CA1 and CA3 cell fields of the hippocampus revealed no dramatic difference in number of positive cells between groups. These results show that, unlike fornix lesions, cholinergic denervation of the hippocampus is not sufficient to block behavioral activation of Arc or Homer 1a transcription. Therefore, cholinergic innervation is not required for Arc or Homer 1a expression.

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

Kitto MR, Carbrera S, Corley S, Castillo A, Atkinson M, Andrews C, Casteneda M, Crawford D, Iliscupidez M, Monahan R, Rodriguez D, Salley T, Butt AE (2004) 192 IgG-saporin lesions of the nucleus basalis magnocellularis impair biconditional discrimination learning in rats. Neuroscience 2004 Abstracts 436.5. Society for Neuroscience, San Diego, CA.

Summary: Previous results from our laboratory suggest that the cholinergic nucleus basalis magnocellularis (NBM) is involved in configural association learning but not in simple association learning. In the current experiment, we hypothesized that 192 IgG-saporin lesions of the NBM in rats would impair biconditional visual discrimination learning, which requires configural association learning. In contrast, we hypothesized that NBM lesions would not impair acquisition of a simple visual discrimination, which requires only simple association learning. In Problem 1, rats were trained in a T-maze to solve a simple visual discrimination between a food-reinforced black goal arm (B+) and a non-reinforced white arm (W-), where the start arm of the maze was always striped (S). Next, in Problem 2, the reinforcement contingencies of the goal arms were reversed (W+ vs. B-), and the start arm visual cue was changed to gray (G). Finally, rats underwent biconditional discrimination training where half of the trials were of Problem 1 type and half were of Problem 2 type. Separately, Problems 1 (S: B+ vs W-) and 2 (G: W+ vs B-) can be solved using simple associations. However, in the biconditional discrimination, where Problems 1 and 2 are intermixed, configural association learning is required. Preliminary results supported our hypotheses. Acquisition of Problems 1 and 2, the simple association problems, did not differ between the NBM lesion group and the control group. However, performance in biconditional discrimination was impaired in the NBM lesion group compared to controls. These results are consistent with the argument that the NBM is involved in configural but not simple association learning.

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