Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C.

doi:10.1016/j.nlm.2015.07.015

Cited by 25 publications

(26 citation statements)

References 86 publications

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“…We observed that rats collided with the paddle within the treadmill less frequently after 10 mg/kg ketamine than at baseline, suggesting that ketamine induced an increase in attention during the walking task. This supports the idea that gamma power and attention are correlated [ 99 ], even when induced by ketamine, and is consistent with a recent study showing that ketamine increases attention in young rodents [ 100 ].…”

Section: Discussionsupporting

confidence: 92%

Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus

et al. 2017

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Alterations in the function of the medial prefrontal cortex (mPFC) and its major thalamic source of innervation, the mediodorsal (MD) thalamus, have been hypothesized to contribute to the symptoms of schizophrenia. The NMDAR antagonist ketamine, used to model schizophrenia, elicits a brain state resembling early stage schizophrenia characterized by cognitive deficits and increases in cortical low gamma (40–70 Hz) power. Here we sought to determine how ketamine differentially affects spiking and gamma local field potential (LFP) activity in the rat mPFC and MD thalamus. Additionally, we investigated the ability of drugs targeting the dopamine D4 receptor (D4R) to modify the effects of ketamine on gamma activity as a measure of potential cognitive therapeutic efficacy. Rats were trained to walk on a treadmill to reduce confounds related to hyperactivity after ketamine administration (10 mg/kg s.c.) while recordings were obtained from electrodes chronically implanted in the mPFC and MD thalamus. Ketamine increased gamma LFP power in mPFC and MD thalamus in a similar frequency range, yet did not increase thalamocortical synchronization. Ketamine also increased firing rates and spike synchronization to gamma oscillations in the mPFC but decreased both measures in MD thalamus. Conversely, walking alone increased both firing rates and spike-gamma LFP correlations in both mPFC and MD thalamus. The D4R antagonist alone (L-745,870) had no effect on gamma LFP power during treadmill walking, although it reversed increases induced by the D4R agonist (A-412997) in both mPFC and MD thalamus. Neither drug altered ketamine-induced changes in gamma power or firing rates in the mPFC. However, in MD thalamus, the D4R agonist increased ketamine-induced gamma power and prevented ketamine’s inhibitory effect on firing rates. Results provide new evidence that ketamine differentially modulates spiking and gamma power in MD thalamus and mPFC, supporting a potential role for both areas in contributing to ketamine-induced schizophrenia-like symptoms.

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Section: Discussionsupporting

confidence: 92%

Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus

et al. 2017

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“…Methods for training animals on the water maze task have been adapted from Guidi et al (2015). Animals were trained in a black tank, 1.7 m in diameter, positioned in a well-lit room containing (when appropriate) an assortment of 2-and 3-dimensional cues.…”

Section: Water Maze Testing For Memory Apparatusmentioning

confidence: 99%

“…Three days following the initial cue discrimination training, animals were trained on a modified version of the DMTP task, which is sensitive to aging (Foster, 2012;Guidi et al, 2015). The platform was lowered to just beneath the water surface and animals were trained to find a hidden platform.…”

Section: Delayed-matching-to-place (Dmtp) Taskmentioning

confidence: 99%

Longitudinal Characterization and Biomarkers of Age and Sex Differences in the Decline of Spatial Memory

Febo

Rani

Yegla

et al. 2020

Front. Aging Neurosci.

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The current longitudinal study examined factors (sex, physical function, response to novelty, ability to adapt to a shift in light/dark cycle, brain connectivity), which might predict the emergence of impaired memory during aging. Male and female Fisher 344 rats were tested at 6, 12, and 18 months of age. Impaired spatial memory developed in middle-age (12 months), particularly in males, and the propensity for impairment increased with advanced age. A reduced response to novelty was observed over the course of aging, which is inconsistent with cross-sectional studies. This divergence likely resulted from differences in the history of environmental enrichment/impoverishment for cross-sectional and longitudinal studies. Animals that exhibited lower level exploration of the inner region on the open field test exhibited better memory at 12 months. Furthermore, males that exhibited a longer latency to enter a novel environment at 6 months, exhibited better memory at 12 months. For females, memory at 12 months was correlated with the ability to behaviorally adapt to a shift in light/dark cycle. Functional magnetic resonance imaging of the brain, conducted at 12 months, indicated that the decline in memory was associated with altered functional connectivity within different memory systems, most notably between the hippocampus and multiple regions such as the retrosplenial cortex, thalamus, striatum, and amygdala. Overall, some factors, specifically response to novelty at an early age and the capacity to adapt to shifts in light cycle, predicted spatial memory in middle-age, and spatial memory is associated with corresponding changes in brain connectivity. We discuss similarities and differences related to previous longitudinal and cross-sectional studies, as well as the role of sex differences in providing a theoretical framework to guide future longitudinal research on the trajectory of cognitive decline. In addition to demonstrating the power of longitudinal studies, these data highlight the importance of middle-age for identifying potential predictive indicators of sexual dimorphism in the trajectory in brain and cognitive aging.

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“…NMDA receptors play an important role in learning and memory, and are critical for spatial memory (Morris et al, 1986 ; Collingridge, 1987 ; Mondadori et al, 1989 ; Morris, 1989 ; Mondadori and Weiskrantz, 1993 ; Lisman et al, 1998 ; Martin et al, 2000 ; Foster, 2012 ; Guidi et al, 2015b ); NMDA receptor-mediated synaptic plasticity and its hypofunction is thought to play a vital role in age-associated cognitive impairments (Foster and Norris, 1997 ; Foster, 2012 ; Kumar and Foster, 2013 ). Advanced age is associated with a decrease in subunit expression and a decline in NMDA receptor function.…”

Section: Nmda Receptor Hypofunction and Its Influence On Cognitive Pementioning

confidence: 99%

NMDA Receptor Function During Senescence: Implication on Cognitive Performance

Kumar

2015

Front. Neurosci.

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105

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N-methyl-D-aspartate (NMDA) receptors, a family of L-glutamate receptors, play an important role in learning and memory, and are critical for spatial memory. These receptors are tetrameric ion channels composed of a family of related subunits. One of the hallmarks of the aging human population is a decline in cognitive function; studies in the past couple of years have demonstrated deterioration in NMDA receptor subunit expression and function with advancing age. However, a direct relationship between impaired memory function and a decline in NMDA receptors is still ambiguous. Recent studies indicate a link between an age-associated NMDA receptor hypofunction and memory impairment and provide evidence that age-associated enhanced oxidative stress might be contributing to the alterations associated with senescence. However, clear evidence is still deficient in demonstrating the underlying mechanisms and a relationship between age-associated impaired cognitive faculties and NMDA receptor hypofunction. The current review intends to present an overview of the research findings regarding changes in expression of various NMDA receptor subunits and deficits in NMDA receptor function during senescence and its implication in age-associated impaired hippocampal-dependent memory function.

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Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence

Cited by 25 publications

References 86 publications

Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus

Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus

Longitudinal Characterization and Biomarkers of Age and Sex Differences in the Decline of Spatial Memory

NMDA Receptor Function During Senescence: Implication on Cognitive Performance

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