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Selective cholinergic lesions of the nucleus basalis magnocellularis disrupt attention in appetitive trace conditioning
Butt AE, Kinney-Hurd BL, Flesher MM, Amodeo DA, Horn LR, Greenfield V, Lladones R, Hernandez G, Loson L (2008) Selective cholinergic lesions of the nucleus basalis magnocellularis disrupt attention in appetitive trace conditioning. Neuroscience 2008 Abstracts 686.14/SS65. Society for Neuroscience, Washington, DC.
Summary: Pavlovian trace conditioning, but not delay conditioning, is a form of declarative memory that requires attention and depends on the medial prefrontal cortex and hippocampus. We have previously shown that selective lesions of the cholinergic basal forebrain projections to the neocortex and to hippocampus disrupt trace conditioning but not delay conditioning. The current experiment examines the contribution of the cortical cholinergic projections of the nucleus basalis magnocellularis (NBM) to the behavioral impairments previously observed following complete basal forebrain lesions involving both the NBM and the hippocampally-projecting medial septum (MS). We hypothesized that selective lesions of the cholinergic NBM neurons would disrupt trace conditioning in a manner similar to that observed following basal forebrain lesions. Additionally, because cholinergic modulation of prefrontal cortex mediates attention in other tasks, we hypothesized that increasing demands on attention in trace conditioning would exacerbate NBM lesion-induced impairments. Rats with bilateral 192 IgG-saporin lesions of the NBM and sham lesion control animals were tested in the trace conditioning paradigm either in the presence or absence of an attention-demanding visual distractor (intermittent, unpredictable flashing light). Rats received 60 trials per day for 10 days, where each trial consisted of a 10 s white noise CS, followed 10 s later by the delivery of a sucrose pellet unconditioned stimulus (US). Conditioned responding was assessed by measuring approach to the food cup. Approach during the CS itself was considered to be non-adaptive, while approach during the trace interval was classified as adaptive responding. Contrary to our hypothesis, results showed that NBM lesions failed to impair acquisition of trace conditioning in the absence of additional attentional demands. These findings suggest that the trace conditioning impairment previously observed following complete basal forebrain lesions were due either to damage to the hippocampally-projecting MS or to a cumulative effect of combined NBM and MS damage. The presence of the visual distractor, however, disrupted acquisition performance in the current experiment as hypothesized. The NBM lesion group in the distracted condition showed excessive non-adaptive responding during CS presentation as compared to controls. The increased attentional load caused by the visual distractor appears to have caused a disinhibition of non-adaptive responding in the NBM lesion group. These results suggest that cholinergic modulation of neocortex is involved in mediating attention during trace conditioning.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Galanthamine does not attenuate attentional or temporal impairments subsequent to cholinergic deafferentation of the cortex or hippocampus
Martin MM, Weathered SL, Wagner SJ, Wallace DG (2008) Galanthamine does not attenuate attentional or temporal impairments subsequent to cholinergic deafferentation of the cortex or hippocampus. Neuroscience 2008 Abstracts 441.12/T4. Society for Neuroscience, Washington, DC.
Summary: The role of the basal forebrain cholinergic system in early symptomology of dementia of the Alzheimer’s type (DAT) remains an area of intense debate. Although involvement of the basalocortical cholinergic system in attentional processing has been established, function of the septohippocampal cholinergic system remains to be determined. A recent study demonstrated a double dissociation between these systems in the organization of rat food protection behavior that may parallel the attentional impairments and temporal disorientation observed during the early stages of DAT. The current study sought to examine whether an acetylcholinesterase inhibitor currently used for the treatment of DAT (i.e., galanthamine) could attenuate these deficits. Consistent with previous research, intraparenchymal injections of 192 IgG-Saporin into the nucleus basalis or medial septum area in female Long Evans rats produced dissociable effects on the organization of food protection behavior. Specifically, nucleus basalis lesions selectively reduced the number of successful food protection behaviors; whereas, medial septum lesions selectively disrupted the temporal organization of food protection behavior. These impairments were not attenuated by the administration of 3 mg/kg s.c. galanthamine twice daily. Results of this study suggest that the modest benefits afforded by galanthamine administration in DAT patients may not reflect improved attention or temporal orientation. Continued studies aimed at understanding the neural dysfunction underlying these deficits may lead to the development of novel therapeutic agents for DAT.
Related Products: 192-IgG-SAP (Cat. #IT-01)
The effect of electrical stimulation in the rats for dementia animal model.
Jeong D, Hwang Y, Chang J (2008) The effect of electrical stimulation in the rats for dementia animal model. Neuroscience 2008 Abstracts 340.11/M2. Society for Neuroscience, Washington, DC.
Summary: Forebrain Cholinergic neurons in the nucleus basalis meynert (NBM) project primarily to the neocortex, and those in the medial septum project to the hippocampus and make a role in memory function. A case study was reported that electrical stimulation of the hypothalamus improves hippocampus dependent memory function. The hypothesis of this study is that electrical stimulation of NBM would induce memory enhancement by effect on neocortex and/or hippocampus. Animal models were induced by selective immunolesion of cholinergic neurons. The cholinergic immunotoxin 192 IgG-saporin was injected in lateral ventricle. 192 IgG-saporin injected rats were compared with Dulbecco’s phosphate bufferd saline (DPBS) injected rats. Neurological deficit and functional outcome were determined by immuohistochemistry using anti-choline acetyl transferase antibody and Morris water maze behavioral test. DBS electrode was implanted in NBM and Stimulation parameters are selected from animal stimulation test. Extent of the cholinergic lesion was showed in the basal forebrain complex region at 192 IgG-saporin injected rats. 192 IgG-saporin injected rats were severely impaired in the probe test of the water maze test. We observe that NBM stimulation induced memory enhancement in dementia models through the behavioral test. Therefore, our animal DBS system could be a useful instrument for investigation of dementia.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic deafferentation of the neocortex with 192 IgG-Saporin impairs feature binding in rats
Botly LC, De Rosa E (2008) Cholinergic deafferentation of the neocortex with 192 IgG-Saporin impairs feature binding in rats. Neuroscience 2008 Abstracts 418.2. Society for Neuroscience, Washington, DC.
Summary: The binding problem refers to the fundamental challenge of the central nervous system to integrate sensory information registered by distinct brain regions to form a unified neural representation of a stimulus. While the cognitive mechanisms and functional neuroanatomy of feature binding have been well examined by the human cognitive literature, the neurochemistry of feature binding remains unknown. We contend that acetylcholine (ACh) is critical for feature binding given this neuromodulator’s presumed role in modulating attention, and the well-established importance of attention to feature binding. Using systemic pharmacology in rats, we have previously established a critical role for ACh in feature binding at encoding, but have yet to identify the target brain regions cholinergic input must reach for successful feature binding to occur. Given the recognized importance of the frontal and parietal cortices to attentional processing, we hypothesized that cholinergic deafferentation of the neocortex would impair feature binding in a similar manner to that of systemic cholinergic blockade. To test this hypothesis, rats received bilateral 192 IgG-Saporin lesions of the nucleus basalis magnocellularis (NBM) of the basal forebrain. Relative to sham-lesioned rats, NBM-lesioned rats were significantly impaired at acquiring a crossmodal Feature-Conjunction (FC) task, while their ability to retrieve the FC task and to acquire a crossmodal Feature-Singleton (FS) task remained intact. These findings provide further support for our cholinergic attentional hypothesis of feature binding and reveal the importance of neocortical cholinergic input from the basal forebrain to the feature binding encoding process.
Related Products: 192-IgG-SAP (Cat. #IT-01)
A synergistic role for GABAergic and cholinergic neurons of the medial septum in spatial reference memory processing: assessment with the Morris water-maze and a novel double-H maze in rats
Lecourtier L, Leroux E, Cosquer B, Cassel JC (2008) A synergistic role for GABAergic and cholinergic neurons of the medial septum in spatial reference memory processing: assessment with the Morris water-maze and a novel double-H maze in rats. Neuroscience 2008 Abstracts 389.10/TT38. Society for Neuroscience, Washington, DC.
Summary: The medial septum – from which GABAergic and cholinergic neurons project to the hippocampus – might be one of the key structures involved in hippocampal-dependent spatial memory processing. Indeed, lidocaine-induced septal inactivation disrupts encoding and retrieval, but not consolidation of a spatial memory in the water maze. Furthermore, the activation of septal 5-HT1A receptors prevents encoding but neither immediate consolidation nor retrieval of such a memory. As i) 5-HT1A receptors are located on most GABAergic and a significant part of cholinergic neurons of the medial septum, and ii) highly selective cholinergic lesions in the medial septum weakly affect spatial learning, it is possible that normal spatial memory processing depends on a cooperation between cholinergic and GABAergic neurons of this region. To address this possibility using selective lesions, 192 IgG-Saporine (IgG group) or Orexine-Saporine (OREX group) was infused into the septum to damage cholinergic or GABAergic neurons, respectively. In a third group (IgG/OREX group), both lesions were combined. Sham-operated rats were used as controls. The lesion effects were assessed on locomotor activity and on acquisition/retrieval of two water-maze tasks, the Morris maze and the double-H maze. In separate groups, retrieval was tested at three post-acquisition intervals in the Morris maze, namely 1, 5 and 25 days, and two post-acquisition periods in the double H maze, namely 5 and 25 days. Only the combined lesion resulted in nocturnal hyperactivity. In the Morris water-maze, at 25 days, there was no retrieval, whatever the group; whereas at the 1-day delay all groups retrieved the platform, at the 5-day delay, IgG and OREX rats showed normal performance while IgG/OREX rats were impaired. In the double-H maze, at the 5-day delay all groups remembered the platform location. These effects will be compared to those found at the 25-day delay (experiment currently running). Our data show that the GABAergic and cholinergic neurons of the septum synergistically contribute to the regulation of hippocampal-dependent (declarative-like) spatial memory processing.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Learning strategy selection in the water maze in medial septal electrolytic and selective cholinergic neurons lesioned rats
Burjanadze M, Beselia G, Chkhikvishvili N, Kotaria N (2008) Learning strategy selection in the water maze in medial septal electrolytic and selective cholinergic neurons lesioned rats. Neuroscience 2008 Abstracts 389.5/TT33. Society for Neuroscience, Washington, DC.
Summary: In this experiment the ability of medial septal electrolytic, selective ACh lesioned (by immunotoxin 192 IgG-saporin) and sham-operated rats, to learn the location of a visible, as well as submerged platform in a water maze was investigated. A total of 36 male outbred albino rats were used in the study. All experiments were approved by the Animal Care and Use Committee of the Institute and were in accordance with the principles of laboratory animal care. The rats’ responses in the competition test were classified as either cue or place directed, based on the swim path for those trials. Sham-operated rats acquired both the visible and hidden platform versions of the task, but when required to choose between the spatial location they had learned and the visible platform in a new location, majority of them swam first to the old spatial location. The medial septal electrolytic lesioned rats acquired the visible platform version of the water maze task but failed to learn the platform location in space. When the visible platform was moved to a new location they often swam directly to it. The medial septal selective ACh lesioned rats, as well as sham-operated, acquired the platform location in space. Sham-operated and selective ACh lesioned rats identified as place responders, had significantly more accurate searches during hidden platform training, providing additional evidence of their effective use of a place learning strategy rather than medial septal electrolytic lesioned rats. These findings suggest that the septo-hippocampal system is essential for accurate spatial learning and suggest its role in processing information about the spatial environment, but deficits observed after septal electrolytic lesions cannot be accounted solely to the loss of hippocampal ACh and raised the unexpected possibility that hippocampal ACh is not essential for all types of hippocampal-dependent memory.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Role of medial septum-diagonal band of Broca neurons in cognitive flexibility
Pang K, Janke K, Servatius RJ (2008) Role of medial septum-diagonal band of Broca neurons in cognitive flexibility. Neuroscience 2008 Abstracts 89.20/SS37. Society for Neuroscience, Washington, DC.
Summary: Cholinergic and GABAergic neurons are major components of the septohippocampal pathway, and comparisons between the two neuronal populations are important for understanding the function of medial septum and vertical limb of the diagonal band (MSDB). Recently, we have been investigating the importance of MSDB neurons in cognitive flexibility. Cognitive flexibility is commonly examined in procedures that require reversal of stimulus-reward associations and those that require shifts in attention set, involving switching attention to different stimulus dimensions. Our recent studies demonstrated that selective damage of GABAergic but not cholinergic MSDB neurons impaired spatial reversal. The present study will determine whether selective lesions of cholinergic or GABAergic MSDB neurons impairs shifting of attentional set. Sprague Dawley rats will be administered saline, GAT1-saporin or 192-IgG saporin into the MSDB to produce no damage, selective GABAergic damage or selective cholinergic damage, respectively. Verification of the lesions will be performed using immunocytochemistry at the end of the study. The behavioral procedure will occur in a plus maze. Rats will start in one of two arms opposite each other (i.e., north and south arms) randomized across trials. On any single trial, the arm opposite the starting arm will be blocked forming a T-maze. Rats will have a choice of entering one of the remaining 2 arms (east or west arms) for food reinforcement. Half of the rats will be reinforced to make an egocentric response (left or right turn) and the other rats will be reinforced to go to a particular arm (east or west; allocentric response) regardless of starting location. After reaching criterion (10 consecutive correct choices), the goal location will be reversed (i.e., left turn to right turn or east to west arm) or shifted to a different dimension (i.e., left turn to east arm or west arm to right turn). It is expected that rats treated with GAT1-saporin, but not 192-saporin, will be impaired on the reversal procedure, similar to previous studies. Impairments in shifting attention set would suggest a global impairment in cognitive flexibility. However, an impairment in the reversal procedure but not shifting of attention set would be similar to recently described deficits in the nucleus basalis magnocellularis using ibotenic acid and 192-IgG saporin lesions (Tait and Brown, Behav Brain Res. 187:100, 2008). The results of this study will provide important insight into the role of the MSDB in learning, attention and cognitive flexibility.
Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)
192-IgG Saporin lesions of the medial septum or nucleus basalis magnocellularis disrupt exploratory trip organization
Wallace DG, Winter SS, Martin MM, Mcmillin JL (2008) 192-IgG Saporin lesions of the medial septum or nucleus basalis magnocellularis disrupt exploratory trip organization. Neuroscience 2008 Abstracts 90.15/SS57. Society for Neuroscience, Washington, DC.
Summary: Previous work has demonstrated that rats use self-movement cues to organize their exploratory behavior. The hippocampus and several cortical areas have been implicated in processing self-movement cues. The current study investigated whether selective cholinergic deafferentation of the hippocampus or cortex differentially influenced the organization of exploratory behavior. Long Evans female rats received injections of 192 IgG-Saporin or saline into the medial septum (MS) or nucleus basalis magnocellularis (NB). Subsequent to recovery, rats were placed on a large circular table that provided access to a refuge under complete dark conditions (infrared cameras and goggles were used to visualize the rat). All rats established a home base in the refuge; however, impairments in exploratory trip organization specific to the homeward segment were observed in MS and NB rats. Both groups displayed increased variability in the temporal pacing of speeds on the homeward return, consistent with impaired distance estimation. Only the NB group displayed a significant reduction in stop duration after short, medium, and long searching progressions. These observations are consistent with different roles for hippocampal and cortical cholinergic function in processing self-movement cues.
Related Products: 192-IgG-SAP (Cat. #IT-01)
The role of cholinergic basal forebrain neurons in adenosine-mediated homeostatic control of sleep: lessons from 192 IgG-saporin lesions.
Kalinchuk AV, McCarley RW, Stenberg D, Porkka-Heiskanen T, Basheer R (2008) The role of cholinergic basal forebrain neurons in adenosine-mediated homeostatic control of sleep: lessons from 192 IgG-saporin lesions. Neuroscience 157:238-253. doi: 10.1016/j.neuroscience.2008.08.040
Summary: The level of adenosine in the basal forebrain increases during sleep deprivation (SD). The cholinergic system of the basal forebrain is thought to be involved in the control of this process. 0.23 µg of 192-IgG-SAP (Cat. #IT-01) was injected into the horizontal diagonal band/ substantia innominata/ magnocellular preoptic nucleus, or 6 µg into the lateral ventricle of rats. The time course was dependent on the injection site, but eventually the SD-induced increase in adenosine was virtually eliminated.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Selective lesion of medial septal cholinergic neurons followed by a mini-stroke impairs spatial learning in rats.
Craig LA, Hong NS, Kopp J, McDonald RJ (2009) Selective lesion of medial septal cholinergic neurons followed by a mini-stroke impairs spatial learning in rats. Exp Brain Res 193(1):29-42. doi: 10.1007/s00221-008-1592-5
Summary: Recent work has suggested that reduced levels of acetylcholine, seen in Alzheimer’s disease patients, increases the susceptibility of hippocampal neurons to future challenges. Rats received two injections totaling 7.5 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum/vertical limb of the diagonal band of Broca. The vasoconstrictor endothelin-1 was used to create small localized strokes in the hippocampus of lesioned animals. The data suggest that loss of these hippocampal neurons compromises functional recovery from stroke.
Related Products: 192-IgG-SAP (Cat. #IT-01)