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Cholinergic deafferentation of prefrontal cortex increases sensitivity to cross-modal distractors during a sustained attention task.
Newman LA, McGaughy J (2008) Cholinergic deafferentation of prefrontal cortex increases sensitivity to cross-modal distractors during a sustained attention task. J Neurosci 28:2642-2650. doi: 10.1523/JNEUROSCI.5112-07.2008
Summary: The authors injected 5 ng of 192-IgG-SAP (Cat. #IT-01) into the prefrontal cortex of rats to investigate the effect of cholinergic loss on distractors to attentional demand. Where all animals experienced impaired performance in the presence of visual distractions, lesioned animals were more sensitive to auditory distractions. While these results indicate compromised top-down processing, lesioned animals showed improved performance in bottom-up processing, possibly caused by a shift in circuit dynamics after the lesion.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Neuroanatomical and behavioral effects of a novel version of the cholinergic immunotoxin mu p75-saporin in mice.
Moreau PH, Cosquer B, Jeltsch H, Cassel JC, Mathis C (2008) Neuroanatomical and behavioral effects of a novel version of the cholinergic immunotoxin mu p75-saporin in mice. Hippocampus 18(6):610-622. doi: 10.1002/hipo.20422
Summary: 192-IgG-SAP (Cat. #IT-01) has been used for over a decade to examine the cholinergic system in the basal forebrain of rats. Establishing the same reagent for mice has been problematic. Here the authors describe the use of a mouse-specific lesioning agent, mu p75-SAP (Cat. #IT-16). After deciding on a dosage of 0.4 µg administered in the form of bilateral intracerebroventricular injections, mice were lesioned and tested. Lesioned animals displayed increased locomotor activity, and spatial learning and memory deficits, with minimal side effects.
Related Products: mu p75-SAP (Cat. #IT-16), 192-IgG-SAP (Cat. #IT-01)
Lesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats.
Tait DS, Brown VJ (2008) Lesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats. Behav Brain Res 187:100-108. doi: 10.1016/j.bbr.2007.08.035
Summary: The authors compared specific lesions of the basal forebrain using 192-IgG-SAP (Cat. #IT-01) with non-specific lesions generated by ibotenic acid. Rats were given 0.12 µg per 0.5 µl bilateral injections of 192-IgG-SAP. The treated animals were then tested in food reward tasks involving two-choice discriminations and reversal of stimulus-reward. Animals with specific lesions did not show impairment with any of the tasks suggesting that non-cholinergic neurons are involved in reversal learning. This work also demonstrates the similarities between monkey and rodent basal forebrain function.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Septal grafts restore cognitive abilities and amyloid precursor protein metabolism.
Aztiria E, Cataudella T, Spampinato S, Leanza G (2009) Septal grafts restore cognitive abilities and amyloid precursor protein metabolism. Neurobiol Aging 30(10):1614-1625. doi: 10.1016/j.neurobiolaging.2007.12.018
Summary: Although cholinergic loss and the presence of ß-amyloid plaques are well documented in Alzheimer’s disease, it is unknown whether restoration of regulatory cholinergic inputs affects in vivo b-amyloid precursor protein (APP). 5 µg of 192-IgG-SAP (Cat. #IT-01) was split between the lateral ventricles of rats. 6 months post-surgery the animals were implanted with cholinergic-rich septal tissue grafts. Grafted animals exhibited normal or near-normal levels of APP. APP levels, as well as improved spatial navigation performance, correlated strongly with graft-induced cholinergic changes.
Related Products: 192-IgG-SAP (Cat. #IT-01)
The pedunculopontine tegmental nucleus and the nucleus basalis magnocellularis: do both have a role in sustained attention?
Rostron CL, Farquhar MJ, Latimer MP, Winn P (2008) The pedunculopontine tegmental nucleus and the nucleus basalis magnocellularis: do both have a role in sustained attention?. BMC Neurosci 9:16. doi: 10.1186/1471-2202-9-16
Summary: This study provided further investigation into the role of the pedunculopontine tegmental nucleus (PPTg) in control of sustained attention. Rats were given 0.13 µg injections of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. The immunotoxin-treated animals were compared to animals receiving ibotenate injections into the PPTg. Results suggest that ibotenate lesions cause impaired selection of conditioned response as shown by an increase in unconditioned behaviors. 192-IgG-SAP treated animals exhibited difficulty obtaining successful lever presses linked to attention.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats.
Kaur S, Junek A, Black MA, Semba K (2008) Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats. J Neurosci 28:491-504. doi: 10.1523/JNEUROSCI.1585-07.2008
Objective: To examine the role of this area of the brain in several facets of sleep behavior.
Summary: The results suggest that cholinergic neurons and non-cholinergic neurons in the basal forebrain play different, but important roles in non-rapid eye movement sleep and EEG delta power after sleep loss. Non-cholinergic basal forebrain neurons inhibit delta waves, whereas cholinergic neurons promote wakefulness.
Usage: The caudal basal forebrain of rats was lesioned with 0.26-µg bilateral injections of 192-IgG-SAP.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake.
Blanco-Centurion C, Gerashchenko D, Shiromani PJ (2007) Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. J Neurosci 27:14041-14048. doi: 10.1523/JNEUROSCI.3217-07.2007
Summary: Orexin neurons in the basal forebrain, tuberomammillary nucleus (TMN), and locus ceruleus (LC) are thought to regulate arousal. Rats were injected with two or three of the following targeted conjugates: anti-DBH-SAP (Cat. #IT-03), 0.25 µl bilateral injections of 1 µg/µl into the LC; orexin-SAP (Cat. #IT-20), 0.25 µl injection of 0.25 µg/µl into the TMN; 192-IgG-SAP (Cat. #IT-01), 3 µl injection of 2 µg/µl into the lateral ventricle. Small differences were observed in sleep architecture, but the data do not support the traditional hypothesis that these three areas of the brain are essential links in the control of wake levels.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20), 192-IgG-SAP (Cat. #IT-01)
The role of the nucleus basalis of Meynert and reticular thalamic nucleus in pathogenesis of genetically determined absence epilepsy in rats: A lesion study.
Berdiev RK, Chepurnov SA, Veening JG, Chepurnova NE, van Luijtelaar G (2007) The role of the nucleus basalis of Meynert and reticular thalamic nucleus in pathogenesis of genetically determined absence epilepsy in rats: A lesion study. Brain Res 1185:266-274. doi: 10.1016/j.brainres.2007.09.010
Summary: Absence seizures due to epilepsy usually occur during passive behavior. This work investigated the role of the cholinergic nucleus basalis of Meynert (NB) and the reticular thalamic nucleus (RT) in these seizures. Rats received either 75 ng of 192-IgG-SAP (Cat. #IT-01) or the control, mouse IgG-SAP (Cat. #IT-18), into the NB and the RT. Loss of cholinergic neurons in the NB resulted in an increased number of spike-and-wave discharges, a marker for absence seizures.
Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)
Immunotoxin lesion of cholinergic nucleus basalis magnocellularis neurons in Lister hooded rats impair performance in a delayed matching-to-place task
Savage S, Ogren S, Olson L, Mattsson A (2007) Immunotoxin lesion of cholinergic nucleus basalis magnocellularis neurons in Lister hooded rats impair performance in a delayed matching-to-place task. Neuroscience 2007 Abstracts 840.1/TT24. Society for Neuroscience, San Diego, CA.
Summary: Central cholinergic systems play an important role in various aspects of cognition, and deficits in cortical cholinergic function have been implicated in the cognitive impairments associated with normal aging and dementia. Cholinergic dysfunctions have also been implicated in several neuropsychiatric disorders, including schizophrenia. Though cognitive dysfunctions, such as impaired working memory, are observed in Alzheimer, as well as schizophrenic patients, the cholinergic mechanisms behind these dysfunctions are not well characterized in animal models. To investigate whether specific cortical cholinergic deficits will affect spatial learning and memory functions, we lesioned the basalo-cortical cholinergic system by stereotaxic infusion of the immunotoxin 192 IgG-saporin in the nucleus basalis magnocellularis (NBM) of adult male Lister hooded rats. Learning and memory was assessed using a delayed matching-to-place (DMP) paradigm in the water maze. We found that animals with cholinergic denervation of neocortex were impaired in the DMP-task. Thus, while the sham-operated animals rapidly learned the task without prior training, saporin-treated rats showed impairment during the initial three days of testing. By the end of the testing period, the lesioned animals had acquired the task. However, the cholinergically denervated animals showed a performance deficit throughout the duration of the experiment with higher trial latencies and longer distance traveled to find the platform as compared to the controls. They also seemed to employ a different strategy to find the hidden platform as compared to control animals. Whether the deficits after cholinergic lesions to the NBM seen in the present experiment are mnemonic and/or attentional in nature remains to be elucidated.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Survival, integration and differentiation of human neural stem cells transplanted into an animal model of cholinergic degeneration
Cusulin C, Aztiria E, Cacci E, Battaglini PP, Kokaia Z, Leanza G (2007) Survival, integration and differentiation of human neural stem cells transplanted into an animal model of cholinergic degeneration. Neuroscience 2007 Abstracts 779.5/E7. Society for Neuroscience, San Diego, CA.
Summary: The recently characterized F7B cell line, derived from human fetal cortex (Cacci et al, 2007) has been observed able to differentiate in vitro into different glial and neuronal subtypes. However, no much data is available about its capacity for differentiation in vivo. In the present work, F7B cells were grafted to the medial septum of newborn (P8) intact rats and to littermates that had been subjected to selective cholinergic deafferentation at P4 using the 192 IgG-saporin immunotoxin. The animals were sacrificed 1 or 3 months after grafting and the dissected brains were processed for immunocytochemistry, using cell-specific (HuNu and GFP) and differentiation markers (Dcx, GFAP, NeuN, and HuD). Overall, grafted F7B cells exhibited an excellent ability to survive and differentiate into the host tissue environment. Survival rate varied among the groups, being consistently higher when the cells were grafted into lesioned, as opposed to intact, animal. Moreover, a better survival was seen at 1 month, compared to 3 months post-grafting, regardless the lesion condition. Interestingly, the presence of a cholinergic depletion in the recipient appeared to affect differentiation of grafted F7B cells. In fact, higher numbers of Dcx+ and HuD+ cells were scattered within the grafts placed in lesioned animals, as compared to controls. In lesioned, but not intact animals, at 3 months post-grafting, sparse F7B cells were found to express the mature neuronal marker NeuN. On the other hand, grafted F7B immunoreactive for GFAP were similarly detected in all transplanted animals. F7B cells appear to be feasible for transplantation, being able to survive and differentiate into a developing brain, and to positively respond to the new environment created by a lesion. Further studies are warranted to test their actual capacity for functional integration.
Related Products: 192-IgG-SAP (Cat. #IT-01)