Selective cholinergic denervation inhibits expression of long-term potentiation in the adult but not infant rat hippocampus

Motooka, Yasuhiko; Kondoh, Takeshi; Nomura, Tamotsu; Tamaki, Norihiko; Tozaki, Hidetoshi; Kanno, Takesi; Nishizaki, Tomoyuki

doi:10.1016/s0165-3806(01)00179-1

Cited by 13 publications

(9 citation statements)

References 16 publications

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“…injections of the toxin (eg Parent and Baxter (2004), Wrenn and Wiley (1998) for reviews). The only memory deficit found in SAPO rats and not mimicked by OX7-saporin was on probe-trial performance in the water maze after a 24-h delay, suggesting that BF cholinergic systems might contribute to some consolidation or recall processes, a possibility that is in line with studies aimed at characterizing hippocampal plasticity, particularly as concerns long-term potentiation after cholinergic denervation (eg Jouvenceau et al, 1996;Motooka et al, 2001) or stimulation (eg Leung et al, 2003). Such a memory deficit was not found after i.c.v.…”

Section: Igg-saporin Lesions: Memory Vs Attentionsupporting

confidence: 55%

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Traissard

Herbeaux

Cosquer

et al. 2006

Neuropsychopharmacol

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In Alzheimer's disease (AD), cognitive decline is linked to cholinergic dysfunctions in the basal forebrain (BF), although the earliest neuronal damage is described in the entorhinal cortex (EC). In rats, selective cholinergic BF lesions or fiber-sparing EC lesions may induce memory deficits, but most often of weak magnitude. This study investigated, in adult rats, the effects on activity and memory of both lesions, alone or in combination, using 192 IgG-saporin (OX7-saporin as a control) and L-N-methyl-D-aspartate to destroy BF and EC neurons, respectively. Rats were tested for locomotor activity in their home cage and for working-and/or reference-memory in various tasks (water maze, Hebb-Williams maze, radial maze). Only rats with combined lesions showed diurnal and nocturnal hyperactivity. EC lesions impaired working memory and induced anterograde memory deficits in almost all tasks. Lesions of BF cholinergic neurons induced more limited deficits: reference memory was impaired in the probe trial of the water-maze task and in the radial maze. When both lesions were combined, performance never improved in the water maze and the number of errors in the Hebb-Williams and the radial mazes was always larger than in any other group. These results (i) indicate synergistic implications of BF and EC in memory function, (ii) suggest that combined BF cholinergic and fiber-sparing EC lesions may model aspects of anterograde memory deficits and restlessness as seen in AD, (iii) challenge the cholinergic hypothesis of cognitive dysfunctions in AD, and (iv) contribute to open theoretical views on AD-related memory dysfunctions going beyond the latter hypothesis.

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Section: Igg-saporin Lesions: Memory Vs Attentionsupporting

confidence: 55%

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Traissard

Herbeaux

Cosquer

et al. 2006

Neuropsychopharmacol

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“…Although cholinergic denervation has been shown in some studies to affect LTP (6)(7)(8)(9), in others decreased cholinergic tone did not affect synaptic plasticity (13). We attribute these differences to variability of lesion-based strategies.…”

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confidence: 80%

“…In addition, spatial memory has also been suggested to depend on cholinergic activity (10), although there are numerous controversies surrounding which behaviors acetylcholine (ACh) regulates (11, 12). Moreover, in few studies cholinergic denervation did not affect expression of LTP (13). Understanding the precise roles of ACh in learning and memory is of importance because in different types of dementia cholinergic function is decreased (14), and manipulations that boost ACh levels at synapses are used as treatment for cognitive deficits.…”

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confidence: 99%

Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation

Martyn¹,

Jaeger

Magalhães³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Basal forebrain cholinergic neurons, which innervate the hippocampus and cortex, have been implicated in many forms of cognitive function. Immunolesion-based methods in animal models have been widely used to study the role of acetylcholine (ACh) neurotransmission in these processes, with variable results. Cholinergic neurons have been shown to release both glutamate and ACh, making it difficult to deduce the specific contribution of each neurotransmitter on cognition when neurons are eliminated. Understanding the precise roles of ACh in learning and memory is critical because drugs that preserve ACh are used as treatment for cognitive deficits. It is therefore important to define which cholinergic-dependent behaviors could be improved pharmacologically. Here we investigate the contributions of forebrain ACh on hippocampal synaptic plasticity and cognitive behavior by selective elimination of the vesicular ACh transporter, which interferes with synaptic storage and release of ACh. We show that elimination of vesicular ACh transporter in the hippocampus results in deficits in long-term potentiation and causes selective deficits in spatial memory. Moreover, decreased cholinergic tone in the forebrain is linked to hyperactivity, without changes in anxiety or depression-related behavior. These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy.Alzheimer's disease | Morris water maze | synaptic vesicle | Barnes maze T he mechanisms that underlie the formation of hippocampaldependent spatial memory have been broadly explored (1). However, the neurochemical basis underlying changes in the strength of synaptic connections necessary for memories to persist is still not precisely understood. In the case of the hippocampus, mechanisms for memory processing include mRNA-dependent (2) and mammalian target of rapamycin (mTOR)-mediated protein synthesis (3) as well as a sequence of biochemical events shared with or closely similar to that of long-term potentiation (LTP) (2). Indeed, the consolidation of two different aversive tasks (4) and of spatial recognition memory (5) is accompanied by LTP of the CA3-CA1 synapse and can be occluded by a preceding LTP.The basal forebrain cholinergic system, which innervates the hippocampus and cortex, has been suggested to modulate LTP in the hippocampus (6-9) and has been implicated in many forms of behavior (10). In addition, spatial memory has also been suggested to depend on cholinergic activity (10), although there are numerous controversies surrounding which behaviors acetylcholine (ACh) regulates (11, 12). Moreover, in few studies cholinergic denervation did not affect expression of LTP (13). Understanding the precise roles of ACh in learning and memory is of importance because in different types of dementia cholinergic function is decreased (14), and manipulations that boost ACh levels at synapses are used a...

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“…Interestingly, one of the possible intracellular molecular signalling pathways involved in 5-HT 1A receptor-mediated alterations of consolidation might involve the inhibition of protein kinase A activity, and thereby the regulation by protein phosphatase 1 (PP1) of Ca 21 /calmodulin-dependent protein kinase II (CaMKII) phosphorylation (e.g., Genoux et al, 2002). Although not studied on the septohippocampal functional interface, it was shown that, within the hippocampus, these pathways were implicated in the negative effects of 8-OH-DPAT on memory (Moyano et al, 2004), a finding corroborated by electrophysiological approaches that focused on the regulation of long-term potentiation (e.g., Motooka et al, 2001). These observations might open an exciting issue for future investigations as regards the role of 5-HT 1A receptorbearing neurons of the medial septum, and more generally of serotonin within the septal region, in cellular and molecular signalling underlying encoding and consolidation.…”

Section: Activation Of 5-ht 1a Receptors and Spatial Memory Consolidamentioning

confidence: 98%

Activation of septal 5‐HT_1A receptors alters spatial memory encoding, interferes with consolidation, but does not affect retrieval in rats subjected to a water‐maze task

2007

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Using Long-Evans rats tested in a water maze, this study assessed the role of 5-HT1A/5-HT7 receptors of the medial septum in encoding, consolidation, and retrieval of spatial information. The testing protocol (acquisition: daily four-trial sessions over three consecutive days; retention: probe trial on day 4) was first validated by showing that intraseptal infusions of lidocaine (LIDO; 40 microg/0.5 microL) disrupted acquisition and retrieval of the task. 8-OH-DPAT (4 microg/0.5 microL) infused before each acquisition session prevented learning/retention of the platform location, an effect attenuated by pretreatment with the 5-HT1A receptor antagonist WAY 100635. With the 5-HT7 antagonist SB 269970, the 8-OH-DPAT-induced acquisition deficit seemed attenuated, but there was no subsequent retention. When infused immediately, 1, 4, or 6 h after each acquisition session, 8-OH-DPAT did not hinder consolidation. When the infusions were performed 2 h postacquisition, however, consolidation was disrupted. Finally, when infused before a probe trial after drug-free acquisition, 8-OH-DPAT had no effect, suggesting no interference with retrieval processes. We also established that 8-OH-DPAT had no effects when the platform was visible, and altered neither home-cage activity nor anxiety-related behavior (elevated plus-maze). Altogether, these results show that 5-HT1A receptors in the septal region contribute both to declarative-like information encoding and subsequently, within a given postacquisition time window, to its consolidation. They do not participate in the retrieval of recently learned declarative-like information. These observations suggest that 5-HT1A receptors of the medial septum contribute to a serotonin-mediated mechanism involved in the encoding and consolidation, not the retrieval of spatial hippocampal-dependent knowledge. These results might have some relevance to approaches aimed at modifying serotonergic functions in the brain for the treatment of disorders such as depression, anxiety, post-traumatic stress, and amnesia.

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Selective cholinergic denervation inhibits expression of long-term potentiation in the adult but not infant rat hippocampus

Cited by 13 publications

References 16 publications

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation

Activation of septal 5‐HT_1A receptors alters spatial memory encoding, interferes with consolidation, but does not affect retrieval in rats subjected to a water‐maze task

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Selective cholinergic denervation inhibits expression of long-term potentiation in the adult but not infant rat hippocampus

Cited by 13 publications

References 16 publications

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation

Activation of septal 5‐HT1A receptors alters spatial memory encoding, interferes with consolidation, but does not affect retrieval in rats subjected to a water‐maze task

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Activation of septal 5‐HT_1A receptors alters spatial memory encoding, interferes with consolidation, but does not affect retrieval in rats subjected to a water‐maze task