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Novel object recognition and social interaction in rats lacking cortical cholinergic innervation; comparing manual and digital video tracking systems
Savage ST, Olson L, Mattsson A (2010) Novel object recognition and social interaction in rats lacking cortical cholinergic innervation; comparing manual and digital video tracking systems. Neuroscience 2010 Abstracts 506.9/LLL49. Society for Neuroscience, San Diego, CA.
Summary: Alterations in cholinergic signaling in the brain have been implicated as a contributing factor in the pathogenesis of schizophrenia. We have shown that cholinergic denervation of cortex cerebri by stereotaxic infusion of the immunotoxin 192 IgG-saporin into nucleus basalis magnocellularis in adult rats leads to an enhanced locomotor sensitivity to amphetamine, as well as, a potentiated dopamine release in nucleus accumbens. We have also shown that this cortical cholinergic denervation leads to an increased locomotor response to the NMDA receptor antagonist phencyclidine (PCP), suggesting that disruption of cortical cholinergic activity can lead to disturbances of glutamatergic transmission. We hypothesize that this loss of cortical cholinergic input alters the activity of cortical glutamatergic neurons and in turn, their regulation of subcortical dopamine neurons. In current studies we are investigating memory functions using the novel object recognition task (NOR) and social interaction in adult male Lister hooded rats with cholinergic denervation of neocortex. The behavioral tasks are being conducted under normal conditions and with a PCP-challenge. The data are analyzed both manually by a trained observer, and with a nose point digital video tracking system (Clever Sys Inc.). Manually scoring behavioral data requires extensive observer training, is subject to inter-observer variability, and is time consuming. An automated tracking system could potentially improve upon these issues, however is prone to other problems, including the difficulty of accurately tracking multiple body points. Furthermore, the Lister hooded fur has two different colors which proves difficult for computerized systems to accurately determine the body points. A comparison of the manual scoring and the computerized tracking system is being conducted to determine the most reliable method for each behavioral task. Preliminary results indicate that the cholinergically denervated rats performed the NOR task under normal conditions as well as the controls, however failed to show a preference for the novel object under PCP-challenge. These results were obtained through analysis with both the manual and automated system. Despite fur color difficulties, the video tracking system was able to analyze the NOR task and accurately calculate the distance traveled, which is not easily obtained through manual scoring. These initial results indicate that cortical cholinergic deficits, in addition to a potentiation of the locomotor response to PCP, can also lead to an enhanced sensitivity to PCP-induced cognitive impairments.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Decrease of Arc protein expression and delay of memory acquisition by immunolesion
Jeong D, Lee D, Chang J (2010) Decrease of Arc protein expression and delay of memory acquisition by immunolesion. Neuroscience 2010 Abstracts 145.5/H6. Society for Neuroscience, San Diego, CA.
Summary: Cholinergic neuronal deficit is one of the common characteristics in both Alzheimer’s disease dementia (AD) and vascular dementia (VaD). Forebrain Cholinergic neurons in the basal forebrain project to the neocortex and the hippocampus which make an important role in memory function. We used 192 IgG-saporin to produce selective lesion of cholinergic basal forebrain neurons including the medial septum (MS) and the nucleus basalis magnocellularis (NBM). We intracerebroventricularly injected 192 IgG-saporin (0.63 µg/µl dose, 6 µl, 8 µl and 10 µl) or phosphate buffered saline (8 µl). Morris water maze and tissue perforation for immunohistochemistry and western blotting were sequentially performed 2 weeks after injection of 192 IgG-saporin. In the acquisition phase of Morris water maze, latency of 6ul group (2nd day), 8 µl group (2nd day) and 10 µl group (3rd day) was significantly delayed but it was recovered within 1week. Time in platform and the number of crossing were significantly different between 8 µl LV injection group and sham group in probe test. In immunohistological study, the extent of the cholinergic lesion was showed in the basal forebrain complex region of all 192 IgG-saporin injected rats. Expression of Arc protein is significantly decreased in the frontal cortex (8 µl and 10 µl groups) but hippocampus. Decrease of parvalbumin in the frontal cortex (8ul and 10 ul groups) and the hippocampus (10 µl) means nonselective lesion because of high dose of immunotoxin. We observed recovery after memory acquisition delay and decrease of synaptic activity in the frontal cortex except in the hippocampus. High dose of immunotoxin injured not only cholinergic neuron but also GABAergic neuron in the frontal cortex and the hippocampus. Hippocampal GABAergic cell synapse on to glutamatergic pyramidal cells. Deficit of the hippocampal inhibitory cell may facilitate hippocampal synaptic plasticity and the recovery.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Early post-natal cholinergic lesion impairs normal development and maturation of the motor cortex in rats
Ramanathan D, Conner JM, Anilkumar AA, Tuszynski MH (2010) Early post-natal cholinergic lesion impairs normal development and maturation of the motor cortex in rats. Neuroscience 2010 Abstracts 32.14/D20. Society for Neuroscience, San Diego, CA.
Summary: Prior studies have indicated that sensory and motor representations develop over a defined postnatal period and are dependent upon behavioral experience to achieve appropriate adult patterns. In adult animals, behaviorally driven forms of cortical map plasticity are critically dependent upon the basal forebrain cholinergic system. Based on the critical role cholinergic mechanisms play in mediating experience-dependent plasticity in adulthood, we postulated that cholinergic mechanisms may also play a critical role in shaping initial cortical map formation during development. In this study, using 25 male Fisher rats between the ages of 15 days and 60 days, we first characterized the normal motor map development in the rat. We found that motor maps underwent a significant change in overall size and refinement over time, with more mature animals having larger overall maps (p < 0.001) and an increase in the size of distal forelimb representations (p < 0.01). Following the initial characterization of normal motor map development in the rat, we used 192-IgG-saporin (SAP) to create selective cholinergic lesions early in map development (PND 24), in 5 animals (with 6 animals receiving ACSF as controls). This early cholinergic depletion impaired the normal maturation and refinement of cortical motor representations: the total caudal forelimb area (comprising elbow and wrist) was decreased by 33% in cholinergically depleted animals, from 5.1 ± 0.3 mm2 to 3.4 ± 0.3 mm2 (t-test p < 0.01). This decrease in caudal forelimb area in cholinergically-depleted animals was primarily driven by a significant 37% reduction in the size of the distal forelimb (wrist) representation, from 3.1 ± 0.1 mm2 to 2.0 ± 0.1 mm2 (p < 0.001). In a follow-up experiment with 12 additional animals (6 with cholingeric lesions and 6 controls), we found that early (PND 24) cholinergic depletions resulted in long-term impairments in skilled motor learning, with significant differences in daily motor performance beginning at day 3 of training (repeated measures ANOVA < 0.05). These results suggest a novel role for the basal forebrain cholinergic system in establishing normal cortical map formation during development.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Subplate neurons promote the formation of barrels within rat primary somatosensory cortex
Sheikh A, Kanold PO (2010) Subplate neurons promote the formation of barrels within rat primary somatosensory cortex. Neuroscience 2010 Abstracts 33.1/E1. Society for Neuroscience, San Diego, CA.
Summary: Subplate neurons are a transient neuronal population present in the neonatal cortex. Subplate neurons receive thalamic afferents and project into the developing cortical plate. Selective removal of subplate neurons in cat visual cortex prevents the normal development of ocular dominance columns and the functional maturation of thalamocortical connections (Ghosh & Shatz 1992, Kanold et al. 2003) . A role of subplate neurons in the development of other sensory cortices is unknown. In rodents, thalamocortical afferents representing the whiskers segregate into barrels in the primary somatosensory cortex (S1). This segregation occurs postnatally and can be disrupted by manipulations of neuronal activity. We previously showed that subplate removal disrupts the development of patterned cortical activity in S1 (Tolner, Yukin, Kaila, Kanold, Abstr. SFN 2009). Thus we hypothesized that disruption of patterned activity in S1 alters the development of barrels. Thus here we investigated if subplate neurons play a role in the development of barrels in rat S1. Subplate neurons were ablated in the somatosensory cortex of rat pups at postnatal day (P) 0 by immunotoxin injections. 10-14 days later we investigated the pattern of barrels in S1 via cytochrome oxidase staining. After subplate ablation there was a disturbance in the barrel patterning when compared to the un-manipulated or control-toxin injected hemispheres. Therefore, subplate neurons are involved in the formation of barrels in S1.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic innervation of the hippocampus is not neccesary for episodic memory, but is required for context-place learning in rats
Easton A, Phil D, Fitchett A, Eacott MJ, Baxter MG (2010) Cholinergic innervation of the hippocampus is not neccesary for episodic memory, but is required for context-place learning in rats. Neuroscience 2010 Abstracts 99.27/KKK13. Society for Neuroscience, San Diego, CA.
Summary: Loss of cholinergic cortical input is associated with diseases in which episodic memory impairment is a prominent feature, but the degree to which this neurochemical lesion can account for memory impairment in humans with neurodegenerative diseases remains unclear. Removal of cholinergic input to hippocampus impairs some of its functions in memory, perhaps by reducing the plasticity of information representation within the hippocampus, but the role of cholinergic hippocampal input in episodic-like memories has not been investigated. To address this question we tested rats with selective lesions of basal forebrain neurons in the medial septum and vertical limb of the diagonal band (MS/VDB), which contains hippocampal-projecting cholinergic neurons, on a task of integrated memory for objects, places, and contexts (“what-where-which” memory). This task serves as a rodent model of human episodic memory (episodic-like memory) and is sensitive to damage to the hippocampal system. Rats with lesions of cholinergic MS/VDB neurons performed as well on the what-where-which task as controls, but were impaired in a task that simply required them to associate places with contexts (“where-which” memory). Thus, episodic-like memories that rely on the hippocampus do not require cholinergic neuromodulation to be formed. Nevertheless, some more specific aspects of where-which memory, which may be more dependent on the plasticity of hippocampal spatial representations, require acetylcholine. These results suggest that cholinergic projections to hippocampus are not necessary for episodic memory, and furthermore, that hippocampal spatial representations may be to some extent dissociable from episodic memory function.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Spatial memory alterations by activation of septal 5HT(1A) receptors: no implication of cholinergic septohippocampal neurons.
Koenig J, Lecourtier L, Cosquer B, Pereira PM, Cassel J (2011) Spatial memory alterations by activation of septal 5HT(1A) receptors: no implication of cholinergic septohippocampal neurons. Psychopharmacology (Berl) 214(2):437-454. doi: 10.1007/s00213-010-2049-7
Summary: These experiments examined what effect damaged cholinergic neurons would have on memory deficits induced by the 5-HT1A/5-HT7 receptor agonist 8-OH-DPAT. Rats received 0.4 µg injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum, delivered through an infusion device. Through use of a water maze test, the authors show that several neuronal populations are involved in processing hippocampal information, and non-cholinergic neurons in this region may be more important than the cholinergic ones for memory processing.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Septohippocampal pathways contribute to system consolidation of a spatial memory: Sequential implication of gabaergic and cholinergic neurons.
Lecourtier L, de Vasconcelos AP, Leroux E, Cosquer B, Geiger K, Lithfous S, Cassel JC (2011) Septohippocampal pathways contribute to system consolidation of a spatial memory: Sequential implication of gabaergic and cholinergic neurons. Hippocampus 21(12):1277-1289. doi: 10.1002/hipo.20837
Summary: Few studies have examined the role of GABAergic septohippocampal projections in memory consolidation. The authors administered 192-IgG-SAP (400 ng; Cat. #IT-01) and/or orexin-SAP (70 ng; Cat. #IT-20) to the medial septum/vertical limb of the diagonal band of Broca of rats. Spatial memory tests were then administered over several weeks. The data indicate that both GABAergic and cholinergic septohippocampal systems contribute to memory stabilization, possibly in a sequential manner.
Related Products: 192-IgG-SAP (Cat. #IT-01), Orexin-B-SAP (Cat. #IT-20)
Effect of applying p75NTR saporin to a punctured intervertebral disc on calcitonin gene-related peptide expression in rat dorsal root ganglion neurons.
Sugiura A, Ohtori S, Yamashita M, Yamauchi K, Inoue G, Suzuki M, Norimoto M, Orita S, Eguchi Y, Kuniyoshi K, Ochiai N, Kishida S, Takaso M, Aoki Y, Ishikawa T, Arai G, Miyagi M, Kamoda H, Nakamura J, Takahashi K (2010) Effect of applying p75NTR saporin to a punctured intervertebral disc on calcitonin gene-related peptide expression in rat dorsal root ganglion neurons. J Orthop Sci 15(3):407-413. doi: 10.1007/s00776-010-1469-x
Summary: Lumbar intervertebral discs are suspected to be a source of low back pain, in part because of the innervation of these discs by neurons containing substance P and CGRP receptors. Rats received 2.5 µg of 192-IgG-SAP (Cat. #IT-01) into the L5/6 vertebral disc after the disc was punctured. While half of the dorsal root ganglion neurons innervating the disc were positive for CGRP post-puncture, animals receiving 192-IgG-SAP displayed reduced CGRP expression, indicating a role for the p75 receptor in discogenic pain.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic hypofunction impairs memory acquisition possibly through hippocampal Arc and BDNF downregulation.
Gil-Bea FJ, Solas M, Mateos L, Winblad B, Ramirez MJ, Cedazo-Minguez A (2011) Cholinergic hypofunction impairs memory acquisition possibly through hippocampal Arc and BDNF downregulation. Hippocampus 21(9):999-1009. doi: 10.1002/hipo.20812
Summary: The authors investigated the role of activity-regulated cytoskeleton associated protein (Arc) and brain-derived neurotrophic factor (BDNF) in cholinergic-induced memory formation. Rats received 67-ng bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the third ventricle after behavioral training. Lesioned animals had decreased protein and mRNA for both Arc and BDNF. Memory acquisition and recovery of acquisition were both affected. The data indicate that cholinergic denervation of the hippocampus affects the muscarinic facets of spatial memory acquisition.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Medial septal cholinergic neurons are necessary for context-place memory but not episodic-like memory.
Easton A, Fitchett AE, Eacott MJ, Baxter MG (2011) Medial septal cholinergic neurons are necessary for context-place memory but not episodic-like memory. Hippocampus 21(9):1021-1027. doi: 10.1002/hipo.20814
Summary: Although it is clear that neurodegenerative diseases cause memory impairment, it is uncertain to what extent cholinergic deficits cause this loss of function. The authors administered a total of 150 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum and vertical limb of the diagonal band of Broca in rats. The lesioned animals were then tested in a rodent model for human episodic memory. The rats performed well on these tests, but struggled with tests that tested the association of places with context. The results suggest that hippocampal spatial representations might not be essential for episodic memory function.
Related Products: 192-IgG-SAP (Cat. #IT-01)