Medial septal lesions disrupt spatial, but not nonspatial, working memory in rats.

Kelsey, John E.; Vargas, Hannah

doi:10.1037/0735-7044.107.4.565

Cited by 90 publications

(30 citation statements)

References 48 publications

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“…The present impairment of foreground contextual conditioning is in agreement with previous studies showing a deficit in hippocampal-dependent learning following MS lesions (Rawlins and Olton 1982;Hagan et al 1988;Kelsey and Vargas 1993 (Selden et al 1991;Phillips and LeDoux 1992;Richmond et al 1999). It is important to note, however, that Bannerman et al (2004) showed that MS lesions had no effect on conditioned contextual freezing.…”

Section: Ms and Adaptive Processing Of Contextual Cuessupporting

confidence: 82%

“…In line with this, electrolytic (Rawlins and Olton 1982;Kelsey and Vargas 1993), excitotoxic (Hagan et al 1988), or also AMPA-induced lesions (McAlonan et al 1995a,b) and more recently lesions with the selective cholinergic toxin 192IgG-saporin (Kirby and Rawlins 2003) demonstrated its involvement in both spatial and contextual fear conditioning. Regarding the LS, although several studies pointed out its involvement in fear learning, current results are somewhat equivocal as to whether the LS has a positive or negative influence on fear learning, a disparity that may depend on the behavioral test used (Sheehan et al 2004).…”

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confidence: 76%

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Dissociated roles for the lateral and medial septum in elemental and contextual fear conditioning

Calandreau¹,

Jaffard²,

Desmedt³

2007

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Extensive evidence indicates that the septum plays a predominant role in fear learning, yet the direction of this control is still a matter of debate. Increasing data suggest that the medial (MS) and lateral septum (LS) would be differentially required in fear conditioning depending on whether a discrete conditional stimulus (CS) predicts, or not, the occurrence of an aversive unconditional stimulus (US). Here, using a tone CS-US pairing (predictive discrete CS, context in background) or unpairing (context in foreground) conditioning procedure, we show, in mice, that pretraining inactivation of the LS totally disrupted tone fear conditioning, which, otherwise, was spared by inactivation of the MS. Inactivating the LS also reduced foreground contextual fear conditioning, while sparing the higher level of conditioned freezing to the foreground (CS-US unpairing) than to the background context (CS-US pairing). In contrast, inactivation of the MS totally abolished this training-dependent level of contextual freezing. Interestingly, inactivation of the MS enhanced background contextual conditioning under the pairing condition, whereas it reduced foreground contextual conditioning under the unpairing condition. Hence, the present findings reveal a functional dissociation between the LS and the MS in Pavlovian fear conditioning depending on the predictive value of the discrete CS. While the requirement of the LS is crucial for the appropriate processing of the tone CS-US association, the MS is crucial for an appropriate processing of contextual cues as foreground or background information.Extensive evidence has implicated the septum in fear and anxiety. On the one hand, previous studies have shown that damage to the septum could result in anxiolytic-like behavioral effects McNaughton 1983, 2000). In this context, Gray (1982) proposed a model according to which activity of the septalhippocampal complex reflects a state of "anxiety" produced when there is a mismatch between predicted and actual sensory events. By preventing animals from detecting such a change, lesions or inactivation of the septum would then cause a decrease in fear or anxiety. On the other hand, septal lesions were also found to profoundly increase fear and anxiety-related behaviors (Thomas 1988), producing the "septal rage syndrome" in many species (Brady and Nauta 1953). This syndrome would result from a generalized disinhibition of fear leading to exacerbated defensive reactions. Hence, a long history of lesion studies indicates that the septum plays a predominant role in fear learning, yet the direction of this control is still a matter of debate.The septal complex is anatomically heterogeneous. While the lateral septum (LS) receives a massive glutamatergic fiber input from the hippocampus by the fornix pathway, the medial septum (MS) sends impressive cholinergic and GABAergic projections to the hippocampus (Jakab and Leranth 1995; Swanson and Risold 2000).Functionally, the MS has been shown to be critically involved in regulating some physiologica...

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Section: Ms and Adaptive Processing Of Contextual Cuessupporting

confidence: 82%

mentioning

confidence: 76%

Dissociated roles for the lateral and medial septum in elemental and contextual fear conditioning

Calandreau¹,

Jaffard²,

Desmedt³

2007

Learn. Mem.

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“…Lesions of the fimbria-fornix, or electrolytic or neurotoxic lesions of the medial septum, impair hippocampal-dependent learning and memory (Mahut 1972;Olton et al 1978;Mitchell et al 1982;Rawlins and Olton 1982;Hepler et al 1985;Kelsey and Landry 1988;Markowska et al 1989;Kelsey and Vargas 1993). These studies have been interpreted as supporting the hypothesis that hippocampal ACh is necessary for normal memory function.…”

Section: Lesions Of the Medial Septum Or Its Projectionssupporting

confidence: 55%

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

Parent¹,

Baxter²

2004

Learn. Mem.

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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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“…For instance, time dependent increases in acetylcholine levels have been observed in the hippocampus after acquisition of spatial memory tasks such as the T-maze or spontaneous alternation task (Hepler et al 1985;Ragozzino et al 1996;Fadda et al 1996). In contrast, lesion studies of the MS/DB have reported to disrupt spatial working memory but not nonspatial working memory (Kelsey and Vargas 1993). On no case did the lesions impair working memory on reference memory visual discrimination tasks or simultaneous conditional discrimination task (Thomas and Gash 1986).…”

Section: Introductionmentioning

confidence: 96%

Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory

et al. 2016

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The medial septum/diagonal band (MS/DB) is a relay region connecting the hypothalamus and brainstem with the hippocampus, and both the MS/DB and dorsal/ventral hippocampus receive strong topographic GABA/peptidergic projections from the nucleus incertus of the pontine tegmentum. The neuropeptide relaxin-3, released by these neurons, is the cognate ligand for a G i/o -protein-coupled receptor, RXFP3, which is highly expressed within the MS/DB, and both

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Medial septal lesions disrupt spatial, but not nonspatial, working memory in rats.

Cited by 90 publications

References 48 publications

Dissociated roles for the lateral and medial septum in elemental and contextual fear conditioning

Dissociated roles for the lateral and medial septum in elemental and contextual fear conditioning

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

Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory

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