References

Pedrino GR, Maurino I, de Almeida Colombari DS, Cravo SL (2006) Role of catecholaminergic neurons of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats. Exp Physiol 91(6):995-1005. doi: 10.1113/expphysiol.2006.034611

Summary: Catecholaminergic neurons in the caudal ventrolateral medulla (CVLM) are thought to help regulate body fluid homeostasis and cardiovascular response due to changes in circulating volume. The authors injected 6.3 ng of anti-DBH-SAP (Cat. #IT-03) into the CVLM of rats, and measured several physiological parameters following an injection of hypertonic or isotonic saline. Data from the lesioned rats indicate that catecholaminergic neurons mediate the cardiovascular response to volume expansion or increases in sodium levels.

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

Garcia-Alloza M, Zaldua N, Diez-Ariza M, Marcos B, Lasheras B, Javier Gil-Bea F, Ramirez MJ (2006) Effect of selective cholinergic denervation on the serotonergic system: implications for learning and memory. J Neuropathol Exp Neurol 65(11):1074-1081. doi: 10.1097/01.jnen.0000240469.20167.89

Summary: The authors compared two lesioning methods using 192-Saporin (Cat. #IT-01) to examine the role of the serotonergic system in learning and memory. 0.067 µg of conjugate administered to each hemisphere of the nucleus basalis of Meynert reduced cholinergic markers in the frontal cortex. 1 µg of conjugate administered to the ventricle of each hemisphere reduced cholinergic markers in the frontal cortex and hippocampus. Both models reduced serotonin levels in the frontal cortex, but only the ICV injections modified learning.

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Banihashemi L, Rinaman L (2006) Noradrenergic inputs to the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus underlie hypothalamic-pituitary-adrenal axis but not hypophagic or conditioned avoidance responses to systemic yohimbine. J Neurosci 26(44):11442-11453. doi: 10.1523/JNEUROSCI.3561-06.2006

Summary: Yohimbine (YO) is an a2 adrenoceptor antagonist that increases transmitter release from adrenergic/noradrenergic (NA) neurons. The authors investigated whether NA inputs to the bed nucleus of the stria terminalis (BNST) were required for YO effects. After receiving 11 ng of anti-DBH-SAP (Cat. #IT-03) in the left and right BNST, rats displayed a marked decrease in the hypothalamic-pituitary-adrenal axis in response to YO administration.

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

Kalinchuk AV, Porkka-Heiskanen T, McCarley RW (2006) Basal forebrain and saporin cholinergic lesions: the devil dwells in delivery details. Sleep 29:1385-1389. doi: 10.1093/sleep/29.11.1385

Summary: The authors of this commentary discuss results presented by Blanco-Centurion et al. The topic is the role of adenosine in the basal forebrain in the control of sleep homeostasis. Discussion covers the potential differences found when 192-IgG-SAP (Cat. #IT-01) is administered locally as compared to an intracerebroventricular injection.

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

See Also:

• Blanco-Centurion C et al. Adenosine and sleep homeostasis in the basal forebrain. J Neurosci 26(31):8092-8100, 2006.

Willis CL, Ray DE, Marshall H, Elliot G, Evans JG, Kind CN (2006) Basal forebrain cholinergic lesions reduce heat shock protein 72 response but not pathology induced by the NMDA antagonist MK-801 in the rat cingulate cortex. Neurosci Lett 407(2):112-117. doi: 10.1016/j.neulet.2006.08.020

Summary: The NMDA receptor antagonist MK-801 may have use in establishing a model for schizophrenia. The mechanism by which cortical neurons are damaged by these antagonists is unknown. The authors tested the theory that cholinergic hyperstimulation of cingulate neurons is involved by administering 80 ng of 192-Saporin (Cat. #IT-01) unilaterally to rats. The results indicate that although cholinergic neurons are involved in the heat shock response to MK-801, the pathological effects follow a different pathway.

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Failor SW, Evans MM, Cang J, Stryker MP, McQuillen PS (2006) Impaired cortical plasticity after early hypoxia–ischemia. Neuroscience 2006 Abstracts 717.14. Society for Neuroscience, Atlanta, GA.

Summary: Background: Unique forms of structural plasticity occur in sensory cortex during critical periods in the developing brain. Recovery from neonatal hypoxic-ischemic brain injury may involve plasticity mechanisms. Objective: To investigate the effect of hypoxic-ischemic injury on plasticity, we examined quantifiable forms of use-dependent structural thalamocortical plasticity in somatosensory and visual cortex following early cerebral hypoxia-ischemia (HI) within a rodent model. Methods: Plasticity in primary somatosensory cortex (S1) was induced by lesion of whisker pad row C on selective days during the first postnatal week with or without preceding hypoxia-ischemia (HI, Vannucci model). The whisker barrel map was visualized with cytochrome oxidase staining and 5-HT immunohistochemistry and quantified by measuring the ratio of D-row to C-row areas in tangential sections. Plasticity in primary visual cortex (V1) was induced by 4-day monocular deprivation (MD) beginning at postnatal day (PND) 28. Ocular dominance was quantified using intrinsic signal optical imaging and expressed as an index of the response to right or left eye stimulation, with or without MD and/or preceding early HI. Changes in markers of inhibitory neurons, extracellular matrix and myelin-associated molecules following HI are correlated with plasticity measurements. Results: S1 plasticity following neonatal HI is attenuated throughout the critical period (PND 1-3). S1 plasticity is significantly decreased (P<0.01, all ages) by an average of 66%. HI does not affect timing of the critical period for S1 plasticity. Following MD, the ocular dominance index (ODI) decreases from 0.14 +/- 0.12 (mean +/- SD, n=9) to -0.16 +/- 0.18 (n=5). Following neonatal HI, this ODI shift is attenuated (n=2). Similar respective effects following MD are observed using a selective immunotoxin (192-saporin) to destroy subplate neurons underlying visual cortex (n=6). Conclusions: Neonatal cerebral hypoxia-ischemia impairs structural plasticity in primary somatosensory and visual cortex. Similar results following selective immunoablation of subplate neurons, taken together with prior observations of selective subplate neuron death following neonatal HI, suggests a role for subplate neurons in structural plasticity during critical periods in sensory cortex.

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Hernandez-Martinez H, Arias-Carrion O, Drucker-Colin R, Murillo-Rodriguez E (2006) Transplant of hypocretin neurons into the lateral hypothalamus of rats with lesions of the hypocretin neurons. Neuroscience 2006 Abstracts 719.2. Society for Neuroscience, Atlanta, GA.

Summary: Narcolepsy, a disabling neurological disorder is characterized by excessive daytime sleepiness, sleeps attacks, sleep fragmentation, and cataplexy. This sleep disorder has been linked to a loss of neurons containing the neuropeptide hypocretin (HCRT). Our group has developed an experimental model to induce narcolepsy in rats. The bilateral administration of the neurotoxin hypocretin-2-saporin (HCRT2-SAP) into the lateral hypothalamus (LH) of rats destroys the HCRT neurons. Therefore, the loss of HCRT neurons leads to developing narcolepsy. In order to replace the HCRT lost neurons by HCRT2-SAP, a suspension of cells from the posterior hypothalamus of 3-5 days old rat pups were stained with GFP and injected into the LH of lesioned rats. Animals were sacrificed 21 days after transplant, and cryostat-cut coronal sections of the LH sections were examined for presence of HCRT-immunofluorescence neurons. Preliminary data shows that HCRT transplanted neurons into the LH of lesioned rats were present at the target area 21 days after implant. These somata were similar in size and appearance to adult rat HCRT-immunoreactive neurons. Our results indicate that HCRT neurons obtained from rat pups can be grafted into a host brain and graft survives during 21 days. Importantly, our study addresses the possibility to replace HCRT neurons in narcolepsy in order to reverse this disease.

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McGaughy JA (2006) The effects of a norepinephrine reuptake blocker, atomoxotine, on an attentional set shifting impairment caused by prefrontal lesions. Neuroscience 2006 Abstracts 749.17. Society for Neuroscience, Atlanta, GA.

Summary: There is substantial evidence to support the role of norepineprhine (NE) in selective attention. The NE system is hypothesized to maintain task-related attentional focus and allow shifts of attention (Aston-Jones and Cohen, 2005). These unique attentional functions correlate with changes in the firing patterns in locus coeruleus. Previous work in our lab has shown that NE lesions of the medial prefrontal cortex produces robust impairments in the ability of rats to perform an attentional set-shift, though acquisition of the attentional set and reinforcement reversal learning were spared. The current study assesses the effectiveness of atomoxotine, a NE reuptake blocker, in remediating these deficits. This drug is currently used in the treatment of attention deficit disorder and may restore balance to the noradrenergic system of the frontal cortex in these patients. Male, Long-Evans rats received lesions of the medial wall of the prefrontal cortex using dopamine beta-hydroxylase saporin (DBH-SAP) to produce selective noradrenergic deafferentation. The performance of DBH-SAP rats was compared to sham-lesioned (SHAM) rats in a test of attentional set-shifting after intraperitoneal injections of atomoxotine (0.0, 0.1,0.3, 0.9 mg/kg) 15 minutes prior to the test of attentional set-shifting. During the attentional set shifting task (Birrell and Brown 1999), rats were exposed to complex stimuli (texturized, scented pots filled with digging media). Initially rats were reinforced for focusing attention on one stimulus dimension, e.g. scent, during the tests of complex discriminations and reinforcement reversals. In tests of attentional set-shifting, subjects were required to inhibit attention to the previously reinforced dimension e.g. scent and learn that a new dimension e.g. texture predicted reinforcement.These results confirm that NE deafferentation of prefrontal cortex impairs the ability of rats to shift attention from the initially reinforced dimension to another dimension, e.g. when texture not odor now predicts reinforcement. Low doses of atomoxotine ameliorate the set-shifting impairments of DBH-SAP rats but hindered the performance of SHAM rats. These data suggest that shifts of attentional set require an optimal level of release of NE in the frontal cortex with both high and low levels of NE causing impairments in these abilities.

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Fitz NF, Gibbs RB, Johnson DA (2006) The role of septo-hippocampal cholinergic lesion, place versus response strategy, and acquisition of a delayed matching to position T-maze task. Neuroscience 2006 Abstracts 751.20. Society for Neuroscience, Atlanta, GA.

Summary: Previously we showed that loss of cholinergic input to the hippocampus results in a significant impairment in acquisition of a delayed matching-to-position T-maze task. Further studies suggest that rats adopt different strategies during different stages of acquisition, initially using a response-type strategy or side preference strategy (independent of external cues) and then switching to a more efficient place strategy (reliant on external cues). We hypothesized that animals with lesions of hippocampal cholinergic inputs would have difficulty shifting to a place strategy, resulting in more days using a response-type strategy, and resulting in the deficit in acquisition. Male Sprague-Dawley rats received intraseptal infusions of either artificial cerebrospinal fluid (CSF) or the selective cholinergic immunotoxin, 192 IgG-saporin (SAP; 0.2 μg in 1.0 μl) into the medial septum (MS). Following recovery from surgery, animals were trained in a DMP T-maze task that consisted of learning to return to an arm of the maze that had been explored during a previous trial. Typically, in both treatment groups, rats would initially adopt a strategy of selecting an arm that resulted in a consistent turn (left or right), which was independent of external cues (response-type strategy). Later in training, the animals adopted a strategy that required a turn that was dependent on external cues (place strategy). Compared to controls, SAP animals had a loss of hippocampal cholinergic innervation and an increase in the number of days to reach criterion (21.7 ± 1.6 days vs. 15.9±0.5 days, p < 0.05). For the SAP group, the increased days to criterion was due to a significant increase in the number of days animals used the response-type strategy (14.8 ± 1.8 days vs. 8.1 ± 1.7 days, p < 0.05). There was no significant difference between groups in the number of days animals utilized the place strategy. These data are consistent with the hypothesis that the cause of the learning impairment on the DMP task observed following cholinergic deafferentation of the hippocampus is due to an impairment in the ability to shift from a response-type strategy to a place strategy.

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

Walker BR, Klueger K (2006) Rodent models: Autism and fragile x syndrome. Neuroscience 2006 Abstracts 764.6. Society for Neuroscience, Atlanta, GA.

Summary: While the exact etiology of autism is not known, autism spectrum disorders (ASD) are most commonly characterized by behavioral deficits in social interaction and communication, obsessional mannerisms, behavioral inflexibility, impairments in planning, attention, hyperactivity and a lack of environmental awareness. These behavioral characteristics have been theorized to be the result of altered forebrain and/or cerebellar circuitry and neurotransmitter transmission. There is some evidence to suggest that treatments effective against seizure and mood disorders that alter these specific neuronal populations are also effective against some core behavioral characteristics of persons with ASD. Therefore, in the present study we tested the hypothesis that electrical stimulation of the rat vagus nerve, as it enters the nucleus tractus solitarius (NTS), will ameliorate social behavior deficits caused by forebrain ACh lesions. To this end, we measured social interaction behavior in rats following bilateral i.c.v. injection of 192-IgG saporin (192-sap; 2 µg/side) or saline, and again following electrical stimulation of the vagus nerve/NTS (100-900 microA). As shown by us previously, bilateral 192-sap injections created a significant decrease in social behavior, as compared to controls. Electrical stimulation of the vagus/NTS, however, reduced these social deficits in 192-sap rats, while having no effect on the social interaction of sham controls. These findings suggest that the circuitry mediating the behavioral deficits seen in autism and ASD may functionally overlap with circuitry of seizure and mood disorders. In addition, our results suggest that vagal nerve stimulation (VNS) may be effective in reducing some of these core behavioral features seen in autism and ASD.

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