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

Uekita, Tomoko; Okaichi, Hiroshige

doi:10.1037/a0015672

Cited by 8 publications

(11 citation statements)

References 33 publications

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“…The injections were counterbalanced for hemisphere injected as well as treatment received across rats. This design led to a maximum of four injections through any one cannula for a rat.This total number of injections into a given cannula is comparable with past studies utilizing a microinjection procedure with these drugs (Barker and Warburton, 2008; Churchwell and Kesner, 2011; Uekita and Okaichi, 2009; Winters, Bartko, Saksida, and Bussey, 2010). The contralateral disconnection manipulation involved a unilateral infusion into the prelimbic cortex and a unilateral infusion into the opposite hemisphere of the subthalamic nucleus.…”

Section: Methodssupporting

confidence: 78%

The prelimbic cortex and subthalamic nucleus contribute to cue-guided behavioral switching

Baker¹,

Ragozzino²

2014

Neurobiology of Learning and Memory

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Frontal cortex - basal ganglia circuitry supports behavioral switching when a change in outcome information is used to adapt response patterns. Less is known about whether specific frontal cortex-basal ganglia circuitry supports behavioral switching when cues signal that a change in response patterns should occur. The present experiments investigated whether the prelimbic cortex and subthalamic nucleus in male Long-Evans rats supports cue-guided switching in a conditional discrimination test. Rats learned in a cross-maze that a start arm cue (black or white) signaled which of two maze arms to enter for a food reward. The cue was switched every 3-6 trials. Baclofen and muscimol infused into the prelimbic cortex significantly impaired performance by increasing switch trial errors, as well as trials immediately following a switch trial (perseveration) and after initially making a correct switch (maintenance error). NMDA receptor blockade in the subthalamic nucleus significantly impaired performance by increasing switch errors and perseveration. Contralateral disconnection of these areas significantly reduced conditional discrimination performance by increasing switch and perseverative errors. These findings suggest that the prelimbic area and subthalamic nucleus support the use of cue information to facilitate an initial switch away from a previously relevant response pattern.

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Section: Methodssupporting

confidence: 78%

The prelimbic cortex and subthalamic nucleus contribute to cue-guided behavioral switching

Baker¹,

Ragozzino²

2014

Neurobiology of Learning and Memory

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“…In fact, this deficit is observed even if spatial pre-training is given prior to drug infusion, in contrast to the upstairs/downstairs open-field spatial memory task [19]. It is also worth pointing out that in this rat study, D-AP5 impaired acquisition of the spatial discrimination task despite the fact that all trials were started from locations that were equidistant between the two beacons, in contrast to the results with GluN1 Δ DGCA1 mice in this study (figure 1 c ).…”

Section: Discussionmentioning

confidence: 99%

Hippocampal NMDA receptors are important for behavioural inhibition but not for encoding associative spatial memories

Taylor

Bus

Sprengel

et al. 2014

Phil. Trans. R. Soc. B

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The idea that an NMDA receptor (NMDAR)-dependent long-term potentiation-like process in the hippocampus is the neural substrate for associative spatial learning and memory has proved to be extremely popular and influential. However, we recently reported that mice lacking NMDARs in dentate gyrus and CA1 hippocampal subfields (GluN1ΔDGCA1 mice) acquired the open field, spatial reference memory watermaze task as well as controls, a result that directly challenges this view. Here, we show that GluN1ΔDGCA1 mice were not impaired during acquisition of a spatial discrimination watermaze task, during which mice had to choose between two visually identical beacons, based on extramaze spatial cues, when all trials started at locations equidistant between the two beacons. They were subsequently impaired on test trials starting from close to the decoy beacon, conducted post-acquisition. GluN1ΔDGCA1 mice were also impaired during reversal of this spatial discrimination. Thus, contrary to the widely held belief, hippocampal NMDARs are not required for encoding associative, long-term spatial memories. Instead, hippocampal NMDARs, particularly in CA1, act as part of a comparator system to detect and resolve conflicts arising when two competing, behavioural response options are evoked concurrently, through activation of a behavioural inhibition system. These results have important implications for current theories of hippocampal function.

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“…It is important to realise that the DMP task requires the single‐trial encoding of novel platform locations on each successive day whereas the reference memory task involves incremental learning of a single platform location over repeated trials. Correspondingly, in experienced animals that are familiar with its demands the reference memory task may require little hippocampal synaptic plasticity (but see Uekita and Okaichi, ). This might also explain the above‐chance (but still impaired) performance of d ‐AP5‐treated rats in the place‐discrimination task (Fig.…”

Section: Discussionmentioning

confidence: 99%

N‐methyl‐d‐aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d‐AP5 interacts directly with the neural mechanisms of spatial learning

Morris

Steele

Bell

et al. 2013

Eur J of Neuroscience

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Three experiments were conducted to contrast the hypothesis that hippocampal N-methyl-d-aspartate (NMDA) receptors participate directly in the mechanisms of hippocampus-dependent learning with an alternative view that apparent impairments of learning induced by NMDA receptor antagonists arise because of drug-induced neuropathological and/or sensorimotor disturbances. In experiment 1, rats given a chronic i.c.v. infusion of d-AP5 (30 mm) at 0.5 μL/h were selectively impaired, relative to aCSF-infused animals, in place but not cued navigation learning when they were trained during the 14-day drug infusion period, but were unimpaired on both tasks if trained 11 days after the minipumps were exhausted. d-AP5 caused sensorimotor disturbances in the spatial task, but these gradually worsened as the animals failed to learn. Histological assessment of potential neuropathological changes revealed no abnormalities in d-AP5-treated rats whether killed during or after chronic drug infusion. In experiment 2, a deficit in spatial learning was also apparent in d-AP5-treated rats trained on a spatial reference memory task involving two identical but visible platforms, a task chosen and shown to minimise sensorimotor disturbances. HPLC was used to identify the presence of d-AP5 in selected brain areas. In Experiment 3, rats treated with d-AP5 showed a delay-dependent deficit in spatial memory in the delayed matching-to-place protocol for the water maze. These data are discussed with respect to the learning mechanism and sensorimotor accounts of the impact of NMDA receptor antagonists on brain function. We argue that NMDA receptor mechanisms participate directly in spatial learning.

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

Cited by 8 publications

References 33 publications

The prelimbic cortex and subthalamic nucleus contribute to cue-guided behavioral switching

The prelimbic cortex and subthalamic nucleus contribute to cue-guided behavioral switching

Hippocampal NMDA receptors are important for behavioural inhibition but not for encoding associative spatial memories

N‐methyl‐d‐aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d‐AP5 interacts directly with the neural mechanisms of spatial learning

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