Complex Behavioral Strategy and Reversal Learning in the Water Maze without NMDA Receptor-Dependent Long-Term Potentiation

Hoh, Tim; Beiko, Jason; Boon, Francis; Weiss, Susannah; Cain, Donald P.

doi:10.1523/jneurosci.19-10-j0003.1999

Cited by 50 publications

(38 citation statements)

References 33 publications

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“…This reduction is comparable to reductions found in previous research using the same equipment, pretraining protocol, and rat strain (Cain, 1997;Cain et al, 1996Cain et al, , 1997Cain et al, , 2000Hoh et al, 1999;Perrot-Sinal et al, 1996;Saucier et al, 1996). As pretraining progressed, rats swam away from the wall and readily used the hidden platform as a refuge.…”

Section: Strategies Pretrainingsupporting

confidence: 78%

“…Previous work has shown that some drug treatments cause sensorimotor disturbances that could be relevant to performance in the WM task (Beiko et al, 1997;Cain, 1997Cain, , 1998Cain et al, 1996Cain et al, , 1997Cain et al, , 2000Cain et al, , 2002Hoh et al, 1999;Saber and Cain, 2003;Saucier and Cain, 1995;Saucier et al, 1996). Therefore rats were also tested on a beam walking task (Kolb and Whishaw, 1985) that assessed sensorimotor function outside the WM environment under the same drug treatment that was given to the rats before WM training.…”

Section: Experiments 2: Spatial Learning Taskmentioning

confidence: 99%

“…A rat was introduced into the pool and swam until it found the hidden platform or 120 s elapsed, at which time it was placed on the platform where it remained for 30 s. Swimming was observed on the television monitor, and search times were recorded; the experimenter was not visible to the swimming rat. The acquisition of WM behavioral strategies during pretraining has been documented (Hoh et al, 1999;Morris, 1989;Perrot-Sinal et al, 1996).…”

Section: Testing Procedures and Behavioral Analysismentioning

confidence: 99%

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Combined but not Individual Administration of β-Adrenergic and Serotonergic Antagonists Impairs Water Maze Acquisition in the Rat

Kenton

Boon

Cain

2007

Neuropsychopharmacol

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This study examined the effects of serotonergic depletion and b-adrenergic antagonism on performance in both visible platform and hidden platform versions of the water maze task. Male Long-Evans rats received systemic injections of p-chlorophenylalanine (500 mg/ kg Â 2) to deplete serotonin, or propranolol (20 or 40 mg/kg) to antagonize b-adrenergic receptors. Some rats received treatments in combination. To separate strategies learning from spatial learning, half of the rats underwent Morris' water maze strategies pretraining before drug administration and spatial training. Individual depletion of serotonin or antagonism of b-adrenergic receptors caused few or no impairments in either naive or pretrained rats in either version of the task. In contrast, combined depletion of serotonin and antagonism of b-adrenergic receptors impaired naive rats in the visible platform task and impaired both naive and strategies-pretrained rats in the hidden platform task, and also caused sensorimotor impairments. This is the first finding of a 'global' water maze task/ sensorimotor impairment with combined administration of two agents that, at the high doses that were given individually, produced few or no impairments. The data imply that (1) serotonergic and b-adrenergic systems may interact in a manner that is important for adaptive behavior; (2) impairments in these systems found in Alzheimer patients may be important for their cognitive and behavioral impairments; and (3) the approach used here can model aspects of the cognitive and behavioral impairments in Alzheimer disease.

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Section: Strategies Pretrainingsupporting

confidence: 78%

Section: Experiments 2: Spatial Learning Taskmentioning

confidence: 99%

Section: Testing Procedures and Behavioral Analysismentioning

confidence: 99%

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Combined but not Individual Administration of β-Adrenergic and Serotonergic Antagonists Impairs Water Maze Acquisition in the Rat

Kenton

Boon

Cain

2007

Neuropsychopharmacol

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“…The latter point is important given that the water maze task is highly stressful, as documented by a rapid and large surge in serum corticosterone early in training (Beiko et al, 1997b). The use of pretraining together with a detailed behavioral analysis has shown that strategy impairments and sensorimotor disturbances, but not spatial learning impairments, are the main cause of increased search times in naive animals given SCO (Beiko et al, 1997a;Cain et al, 2000;Saucier et al, 1996), or the benzodiazepine diazepam (Cain, 1997;Cain et al, 2000), or any of a variety of NMDA receptor antagonists (Bannerman et al, 1995;Cain et al, 1996Cain et al, , 1997Cain et al, , 2000Hoh et al, 1999;Saucier and Cain, 1995). In each of the above studies pretrained drugged rats were indistinguishable from controls on behavioral measures of spatial learning.…”

Section: Introductionmentioning

confidence: 89%

Combined β-Adrenergic and Cholinergic Antagonism Produces Behavioral and Cognitive Impairments in the Water Maze: Implications for Alzheimer Disease and Pharmacotherapy with β-Adrenergic Antagonists

Saber

Cain

2003

Neuropsychopharmacol

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This study examined the effects of b-adrenergic and muscarinic blockade on spatial learning and strategy use in the water maze. Male Long-Evans rats received systemic injections of propranolol (PRO; 10 or 20 mg/kg) or scopolamine (SCO; 0.3 or 1.0 mg/kg) either singly or in combination. To separate strategies learning from spatial learning approximately half of the rats underwent water maze strategies pretraining prior to drug administration and spatial training. PRO did not impair performance in any group. SCO impaired naive but not pretrained rats. PRO and SCO given together in high doses impaired all aspects of behavior in both naive and pretrained rats, and caused sensorimotor disturbances in some groups. PRO (10 mg/kg) and SCO (0.3 mg/kg) together caused a specific spatial reversal learning impairment in pretrained rats without causing strategies impairments or sensorimotor disturbances. Nadolol administered with SCO failed to produce the same impairments as PRO, suggesting that PRO produced its effects by acting on central nervous system sites. These results point to a greater than additive impairing effect of PRO and SCO on adaptive behavior, and a specific role for b-adrenergic and cholinergic systems working in conjunction in spatial learning. They also suggest that some of the behavioral and cognitive impairments seen in Alzheimer patients or patients receiving pharmacotherapy with b-adrenergic antagonists in which cholinergic activity is also compromised may result from the combined impairment of b-adrenergic and cholinergic systems.

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“…Indeed, with sufficient training, learning in the Morris water maze becomes hippocampus-independent (Hoh et al 1999) and would therefore be assumed to be REM sleep-independent as well. In our hands, animals show robust initial spatial training and initial probe trial performance and were not affected by concurrent REM sleep deprivation in those same initial learning metrics, except under the weakest learning conditions (four trials/day previously maze-exposed animals).…”

Section: Factors Contributing To Lack Of Concurrent Rem Sleep Deprivamentioning

confidence: 99%

Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training

Walsh

Booth²,

Poe³

2011

Learn. Mem.

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This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampusdependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation-associated impairment in initial spatial learning with four trials/ day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items.While it has been widely shown that both total sleep deprivation and sleep fragmentation impair learning, there remains much debate over the role of REM sleep deprivation for learning (for reviews, see Smith 1995;Hobson and Pace-Schott 2002;Vertes 2004;Rauchs et al. 2005;Stickgold and Walker 2005;Vertes and Siegel 2005). Increases in REM sleep have been described following learning (e.g., Lucero 1970;Hennevin et al. 1971;Leconte and Hennevin 1971;Fishbein et al. 1974;Smith et al. 1980;Smith and Butler 1982;Smith and Lapp 1986;Portell-Cortes et al. 1989;Smith and Wong 1991;Bramham et al. 1994;Smith and Rose 1997;Mavanji and Datta 2003) that imply a functional relationship. Some studies suggest that REM sleep is tightly linked with specific types of learning such as spatial learning (e

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Complex Behavioral Strategy and Reversal Learning in the Water Maze without NMDA Receptor-Dependent Long-Term Potentiation

Cited by 50 publications

References 33 publications

Combined but not Individual Administration of β-Adrenergic and Serotonergic Antagonists Impairs Water Maze Acquisition in the Rat

Combined but not Individual Administration of β-Adrenergic and Serotonergic Antagonists Impairs Water Maze Acquisition in the Rat

Combined β-Adrenergic and Cholinergic Antagonism Produces Behavioral and Cognitive Impairments in the Water Maze: Implications for Alzheimer Disease and Pharmacotherapy with β-Adrenergic Antagonists

Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training

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