Dissociation of the Roles of NMDA Receptor and Hippocampus in Rats' Spatial Learning: The Effects of Environmental Familiarity and Task Familiarity

Uekita, Tomoko; Okaichi, Yoko; Okaichi, Hiroshige

doi:10.1515/revneuro.2006.17.1-2.163

Cited by 5 publications

(6 citation statements)

References 19 publications

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“…Spatial pretraining did not ameliorate the AP5-induced acquisition deficits in a novel spatial task in a novel environment. The present results were consistent with our earlier studies (Uekita & Okaichi, 2005; Uekita, Okaichi, & Okaichi, 2006), demonstrating that hippocampal NMDA receptors are required for the formation of spatial representation.…”

Section: Discussionsupporting

confidence: 94%

“…Concerning the methods of NMDA blockade, in our earlier studies we injected MK-801 intraperitoneally (Uekita & Okaichi, 2002, 2005; Uekita et al, 2006). Therefore, we could not confirm if the impairment in spatial tasks was a result of the blockade of the hippocampal NMDA receptor, since systemically injected MK-801 blocks the NMDA receptors as well as those in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

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Pretraining does not ameliorate spatial learning deficits induced by intrahippocampal infusion of AP5.

Uekita¹,

Okaichi²

2009

Behavioral Neuroscience

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Previous studies show discrepancies concerning the effects of pretraining on spatial learning deficits induced by blockade of the N-methyl-D-aspartate (NMDA) receptor. These inconsistencies might be attributed to the differences in the nature of the pretraining tasks and the method of blocking NMDA receptors. In the present study, the authors pretrained rats in a spatial water maze task. The authors then trained them with a novel spatial task in a novel environment under chronic blockade of hippocampal NMDA receptors by intrahippocampal infusion of 2-amino-5-phosphonopentanoic acid (AP5) using osmotic pumps. Although the rats had acquired the basic techniques needed to solve a water-maze spatial task during pretraining, those given high or low doses of AP5 showed acquisition deficits. As the spatial pretraining failed to ameliorate the acquisition deficits of a new task in a novel environment, it was suggested that NMDA receptors were necessary in forming spatial representations. Because neither dose of AP5 affected the performance of a spatial task in the retention phase, sensory motor disturbances could not have caused these deficits.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Pretraining does not ameliorate spatial learning deficits induced by intrahippocampal infusion of AP5.

Uekita¹,

Okaichi²

2009

Behavioral Neuroscience

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“…Although it remains uncertain what exactly newly generated neurons contribute to hippocampus‐dependent learning, this finding suggests that the learning produced by the Morris water task training under reduced‐cue hidden platform conditions may be inhibitory to adult neurogenesis. Glutamatergic signaling via NMDA receptors plays a role in spatial learning (Uekita et al, 2006) and has a complex regulatory role in adult neurogenesis (Nacher and McEwen, 2006). Both increases (Joo et al, 2007) and decreases (Cameron et al, 1995) in adult neurogenesis have been reported following modulation of NMDA receptor activity.…”

Section: Discussionmentioning

confidence: 99%

Task difficulty in the Morris water task influences the survival of new neurons in the dentate gyrus

2010

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Adult neurogenesis continues throughout life in the mammalian hippocampus. The precise function of the adult generated neurons remains uncertain although there is growing evidence that they are involved in hippocampus-dependent learning and memory. Training rats on a hidden platform version of the Morris water task has been shown to increase or decrease the survival of newly produced cells in the dentate gyrus (DG) compared to training on a visible platform version. Here we investigated whether the difficulty of the task is related to the degree or direction of the change in neurogenesis. We trained rats on either a visible platform version of the Morris water task or one of three different hidden platform paradigms: four training trials per session version, two training trials per session, and reduced-cue (a version in which the majority of the distal cues were removed from the room). BrdU was administered 6 days prior to training and rats were perfused 24 h after the last training session. As expected, training on the four trial hidden platform version increased cell survival compared to training on the visible platform version. However, training on the more difficult reduced-cue hidden platform version resulted in a decrease in cell survival. Rats that received fewer trials per session did not differ in terms of cell survival in comparison to rats trained on the visible platform version. These findings demonstrate that altering the difficulty of the spatial task has an impact on the corresponding change in cell survival. The lack of obvious distal cues likely changed the strategy used by the rats to determine the location of the platform and resulted in a decrease, instead of an increase in cell survival in the hippocampus. In conclusion, different types of hippocampus-dependent learning can differentially impact cell survival.

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“…A study looking at memory dysfunction found that GF mice, on exposure to Novel Object Recognition and T-maze exploration tests, lacked non-spatial and working memory [145] which are believed to involve NMDARs in the hippocampus [146][147][148][149]. In addition, the animals exhibited a decrease in hippocampal BDNF expression compared to colonised controls consistent with evidence that the microbiota can modulate cerebral neurotrophins [81].…”

Section: Microbial Regulation Of Bdnf and Nmdarsmentioning

confidence: 72%

The Gut-Brain Axis, BDNF, NMDA and CNS Disorders

2016

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Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.

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Dissociation of the Roles of NMDA Receptor and Hippocampus in Rats' Spatial Learning: The Effects of Environmental Familiarity and Task Familiarity

Cited by 5 publications

References 19 publications

Pretraining does not ameliorate spatial learning deficits induced by intrahippocampal infusion of AP5.

Pretraining does not ameliorate spatial learning deficits induced by intrahippocampal infusion of AP5.

Task difficulty in the Morris water task influences the survival of new neurons in the dentate gyrus

The Gut-Brain Axis, BDNF, NMDA and CNS Disorders

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