Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning

Cahill, Jonathan; Baxter, Mark G.

doi:10.1046/j.0953-816x.2001.01807.x

Cited by 49 publications

(38 citation statements)

References 40 publications

(44 reference statements)

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“…These values compare favorably with those in our study, suggesting any differences in behavioral outcome between the two experiments are probably not due to differences in lesion extent. Furthermore, examination of immunohistochemical material in rats in which it was available confirmed extensive (nearly total) loss of cholinergic (ChAT-immunopositive) neurons in the basal forebrain, with preservation of parvalbumin-immunoreactive neurons, as is typical for these lesions produced in our laboratory (see Cahill and Baxter 2001;De Rosa et al 2001). …”

Section: Histological Analysismentioning

confidence: 53%

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Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

Vuckovich

Semel²,

Baxter³

2004

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A recent study suggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that may have damaged cerebellar Purkinje cells. The present study tested rats with highly selective lesions of cholinergic neurons in all major areas of the basal forebrain on a spatial working memory task in the radial arm maze. In postoperative testing, there were no significant differences between lesion and control groups in working memory, even with a delay period of 8 h, with the exception of a transient impairment during the first 2 d of postoperative testing at shorter delays (0 or 2 h). This finding corroborates other results that indicate that the cholinergic basal forebrain does not play a significant role in spatial working memory. Furthermore, it underscores the presence of intact memory functions after cholinergic basal forebrain damage, despite attentional impairments that follow these lesions, demonstrated in other task paradigms.The cognitive functions of the basal forebrain cholinergic system (BFCS) are of considerable interest, given the damage to this system associated with neuropathological conditions such as Alzheimer's disease (Perry et al. 1977(Perry et al. , 1978Bartus et al. 1982Bartus et al. , 1985aBaxter and Gallagher 1997;Bartus 2000). Experimental lesion studies have attempted to address the question of which aspects of cognitive impairment in these human disease states, if any, can be attributed to loss of cholinergic neurons. The present study aims to further clarify the role of the BFCS in spatial cognition.The extent of acetylcholine loss in aged and demented subjects correlates with the extent of their cognitive impairment (Perry et al. 1977(Perry et al. , 1978Bartus et al. 1982). Experiments on animals have therefore examined the effects of BFCS lesions on spatial learning and memory tasks. These tasks are thought to effectively model the cognitive processes that are usually the first to deteriorate in aged and demented humans (Gallagher and Pelleymounter 1988). However, different BFCS lesion experiments have produced seemingly contradictory results. Early studies suggested an important role for this system in learning and memory. Rats with ibotenic acid lesions of the nucleus basalis magnocellularis/substantia innominata (nBM/SI), the component of the basal forebrain that projects predominantly to neocortex, were impaired on a preoperatively learned delayed nonmatching-tosample (DNMS) radial maze task (Bartus et al. 1985b(Bartus et al. , 1986. Similarly, lesions to the nBM/SI or medial septum/vertical limb of the diagonal band (MS/VDB; the component of the basal forebrain that projects predominantly to the hippocampus) also impaired learning and performance in spatial working memory in the radial arm maze (Hepler et al. 1985;M'Harzi and Jarrard 1992).However, studies using ibotenic acid ca...

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Section: Histological Analysismentioning

confidence: 53%

“…Immunostaining was done by using avidin-biotin complex methods discussed elsewhere (Cahill and Baxter 2001). ChAT immunohistochemistry was carried out with monoclonal anti-ChAT antibodies (goat monoclonal anti-ChAT, Vector Labs).…”

Section: Histological Analysismentioning

confidence: 99%

Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

Vuckovich

Semel²,

Baxter³

2004

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“…An additional group of 20 rats received unilateral injections of IBO (8 g in 0.5 l of ACSF; IBO-UNI; n ϭ 11) or ACSF (0.5 l; ACSF-UNI; n ϭ 9). The IBO concentrations were chosen based on previous studies (Buzsaki et al, 1988;Cahill and Baxter, 2001;Pang et al, 2001) and a pilot study using a lower concentration of IBO (0.8 g in 0.5 l of ACSF), which did not yield significant lesions. For 192IgG-SAP, a pilot study was conducted to determine an effective amount histologically, and this amount from the same batch of immunotoxin was used for the main study.…”

Section: Polygraphic Recordings Lesions Sleep Deprivation and Perfmentioning

confidence: 99%

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

Kaur¹,

Junek²,

Black³

et al. 2008

J. Neurosci.

115

111

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The basal forebrain (BF) is known for its role in cortical and behavioral activation, and has been postulated to have a role in compensatory mechanisms after sleep loss. However, specific neuronal phenotypes responsible for these roles are unclear. We investigated the effects of ibotenate (IBO) and 192IgG-saporin (SAP) lesions of the caudal BF on spontaneous sleep-waking and electroencephalogram (EEG), and recovery sleep and EEG after 6 h of sleep deprivation (SD). Relative to artificial CSF (ACSF) controls, IBO injections decreased parvalbumin and cholinergic neurons in the caudal BF by 43 and 21%, respectively, and cortical acetylcholinesterase staining by 41%. SAP injections nonsignificantly decreased parvalbumin neurons by 11%, but significantly decreased cholinergic neurons by 69% and cortical acetylcholinesterase by 84%. IBO lesions had no effect on sleep-wake states but increased baseline delta power in all states [up to 62% increase during non-rapid eye movement (NREM) sleep]. SAP lesions transiently increased NREM sleep by 13%, predominantly during the dark phase, with no effect on EEG. During the first 12 h after SD, animals with IBO and SAP lesions showed lesser rebound NREM sleep (32 and 77% less, respectively) and delta power (78 and 53% less) relative to ACSF controls. These results suggest that noncholinergic BF neurons promote cortical activation by inhibiting delta waves, whereas cholinergic BF neurons play a nonexclusive role in promoting wake. Intriguingly, these results also suggest that both types of BF neurons play important roles, probably through different mechanisms, in increased NREM sleep and EEG delta power after sleep loss.

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“…For example, rats may use egocentric (body movement) cues, path integration, orientation to single visual cues, spatial maps, or any combination thereof to solve such problems (Whishaw et al 1995;Dudchenko et al 1997;Martin et al 1997;Dudchenko 2001). Two studies have suggested that lesions of MS/ VDB cholinergic neurons bias rats away from using an allocentric (place) strategy to solve a radial arm maze (Janis et al 1998;Lehmann et al 2003), although other studies have found that rats with these lesions are able to use such strategies in the crossmaze (Cahill and Baxter 2001) or water maze . Examination of particular strategies used by animals to solve spatial problems might represent a fruitful avenue of investigation, as selective neurochemical lesions may be able to reveal how spatial cognition is fractionated within the hippocampus.…”

Section: Learning and Memory 13mentioning

confidence: 99%

“…Computational modeling suggests that GABA, acting via GABA(B) receptors, possesses the capacity to rapidly modulate hippocampal physiology on a time scale consistent with spatial learning (Wallenstein and Hasselmo 1997;Hasselmo and Fehlau 2001;Molyneaux and Hasselmo 2002). Ibotenic acid lesions of the MS/VDB, which primarily affect the septal GABA neurons but spare the ACh neurons, impair place learning (Cahill and Baxter 2001). In contrast, selective kainic acid-induced lesions of the septohippocampal GABA projection do not impair spatial learning, suggesting that the septal GABAergic projection is also not necessary for memory (Pang et al 2001).…”

Section: Learning and Memory 13mentioning

confidence: 99%

Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?

Parent¹,

Baxter²

2004

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175

132

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The neurotransmitter acetylcholine (ACh) has been accorded an important role in supporting learning and memory processes in the hippocampus. Cholinergic activity in the hippocampus is correlated with memory, and restoration of ACh in the hippocampus after disruption of the septohippocampal pathway is sufficient to rescue memory. However, selective ablation of cholinergic septohippocampal projections is largely without effect on hippocampal-dependent learning and memory processes. We consider the evidence underlying each of these statements, and the contradictions they pose for understanding the functional role of hippocampal ACh in memory. We suggest that although hippocampal ACh is involved in memory in the intact brain, it is not necessary for many aspects of hippocampal memory function.The goal of this review is to consider the role of septohippocampal acetylcholine (ACh) in learning and memory processes. The evidence in this regard falls broadly into two different classes. On the one hand, considerable data implicate septohippocampal ACh in memory function. This system is engaged during memory processing, indexed by ACh release or by modification of cholinergic markers, and manipulations that affect memory produce parallel changes in hippocampal cholinergic activity. Furthermore, agents that increase hippocampal cholinergic function are sufficient to reverse memory impairments caused by disruption of the septohippocampal system. However, data from studies of selective lesions of septohippocampal cholinergic neurons with the immunotoxin 192 IgG-saporin call into question the essential role of this system in learning and memory, because these studies generally failed to find severe impairments in memory function. Our goal in this article is to review the data underlying each of these lines of evidence, and to attempt to reconcile these apparently disparate observations.The discrepancy between these lines of evidence might imply that septohippocampal ACh is involved in memory processing, but is not necessary for it to occur. This viewpoint would allow for correlated changes in ACh release and memory, and for the ability of cholinergic agents to reverse memory impairments caused by disruption of septohippocampal function. However, it also would permit memory to proceed relatively normally in the absence of septohippocampal cholinergic input. By describing this viewpoint and its implications for the functional role of hippocampal ACh in memory, we seek to promote the idea that data from lesions are compatible with data from other experimental approaches. Furthermore, we suggest that a convergent approach that incorporates observations from different experimental methods will reveal functional characteristics of hippocampal ACh that would not be apparent from studies using a single strategy.Before discussing the role of this system in cognition, a brief review of its anatomical and neurochemical organization is warranted. The septum is connected to the hippocampus via the fimbria-fornix, which carries projections ...

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Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning

Cited by 49 publications

References 40 publications

Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

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

Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?

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