Dose-related effects of memantine on a mismatch negativity-like response in anesthetized rats

Tikhonravov, Dmitri; Neuvonen, Tuomas; Pertovaara, Antti; Savioja, Kati; Ruusuvirta, Timo; Näätänen, Risto; Carlson, Synnöve

doi:10.1016/j.neuroscience.2010.03.014

Cited by 56 publications

(47 citation statements)

References 29 publications

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“…Studies in mice (Ehrlichman et al, 2008), rats (Tikhonravov et al, 2008(Tikhonravov et al, , 2010, and monkeys (Javitt et al, 1996) also showed that MMN is strongly affected by NMDAr inhibitors. In our simulations, the sMMN results essentially from NMDAr-dependent currents, which is consistent with this observation.…”

Section: Layer Distribution Of Current Sourcesmentioning

confidence: 96%

A Neuronal Model of Predictive Coding Accounting for the Mismatch Negativity

Wacongne¹,

Changeux²,

Dehaene³

2012

J. Neurosci.

480

423

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The mismatch negativity (MMN) is thought to index the activation of specialized neural networks for active prediction and deviance detection. However, a detailed neuronal model of the neurobiological mechanisms underlying the MMN is still lacking, and its computational foundations remain debated. We propose here a detailed neuronal model of auditory cortex, based on predictive coding, that accounts for the critical features of MMN. The model is entirely composed of spiking excitatory and inhibitory neurons interconnected in a layered cortical architecture with distinct input, predictive, and prediction error units. A spike-timing dependent learning rule, relying upon NMDA receptor synaptic transmission, allows the network to adjust its internal predictions and use a memory of the recent past inputs to anticipate on future stimuli based on transition statistics. We demonstrate that this simple architecture can account for the major empirical properties of the MMN. These include a frequency-dependent response to rare deviants, a response to unexpected repeats in alternating sequences (ABABAA. . . ), a lack of consideration of the global sequence context, a response to sound omission, and a sensitivity of the MMN to NMDA receptor antagonists. Novel predictions are presented, and a new magnetoencephalography experiment in healthy human subjects is presented that validates our key hypothesis: the MMN results from active cortical prediction rather than passive synaptic habituation.

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Section: Layer Distribution Of Current Sourcesmentioning

confidence: 96%

A Neuronal Model of Predictive Coding Accounting for the Mismatch Negativity

Wacongne¹,

Changeux²,

Dehaene³

2012

J. Neurosci.

480

423

View full text Add to dashboard Cite

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“…MMN was found to be a sensitive and predictive biomarker of perceptual learning during auditory cognitive training in 28 individuals with schizophrenia [140]. MMN was enhanced in 13 healthy subjects with memantine 30 mg (Cohen’s d = 0.87; [141]), in rodents with memantine 10 mg/kg [142], and in 41 people with schizophrenia with memantine 20 mg [75]. No studies have been conducted with galantamine on MMN.…”

Section: Mismatch Negativitymentioning

confidence: 99%

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

Koola¹

2018

Complex Psychiatry

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Schizophrenia is, in part, a cognitive illness. There are no approved medications for cognitive impairments associated with schizophrenia (CIAS) and primary negative symptoms. Cholinergic and glutamatergic systems, alpha-7 nicotinic acetylcholine (α-7nACh) and N-methyl-D-aspartate (NMDA) receptors, kynurenic acid (KYNA), and mismatch negativity have been implicated in the pathophysiology of CIAS and negative symptoms. Galantamine is an acetylcholinesterase inhibitor that is also a positive allosteric modulator at the α4β2 and α7nACh receptors. Memantine is a noncompetitive NMDA receptor antagonist. Galantamine and memantine alone and in combination were effective for cognition in animals and people with Alzheimer’s disease. The objective of this article is to critically dissect the published randomized controlled trials with galantamine and memantine for CIAS to highlight the efficacy signal. These studies may have failed to detect a clinically meaningful efficacy signal due to limitations, methodological issues, and possible medication nonadherence. There is evidence from a small open-label study that the galantamine-memantine combination may be effective for CIAS with kynurenine pathway metabolites as biomarkers to detect the severity of cognitive impairments. Given that there are no available treatments for cognitive impairments and primary negative symptoms in schizophrenia, testing of this “five-pronged strategy” (quintuple hypotheses: dopamine, nicotinic-cholinergic, glutamatergic/NMDA, GABA, and KYNA) is a “low-risk high-gain” approach that could be a major breakthrough in the field. The galantamine-memantine combination has the potential to treat positive, cognitive, and negative symptoms, and targeting the quintuple hypotheses concurrently may lead to a major scientific advancement – from antipsychotic treatment to antischizophrenia treatment.

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“…For example, recordings in brain slices of the IC after electrical stimulation of the lateral lemniscus fibers demonstrated that there were two distinct components of the excitatory responses (Ma, Kelly, & Wu, 2002): a rapid, short latency component that was mediated by AMPA (␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, and a component with longer latency and duration that was mediated by NMDA receptors. NMDA receptors have been associated with the generation of MMN (Korostenskaja, Nikulin, Kicic, Nikulina, & Kahkonen, 2007;Schmidt, Diaconescu, Kometer, Friston, Stephan, & Vollenweider, 2013;Tikhonravov et al, 2010Tikhonravov et al, , 2008Wacongne, Changeux, & Dehaene, 2012). Interestingly, Umbricht, Schmid, (Malmierca, 2004).…”

Section: Excitatory Inhibitory and Cholinergic Inputs To The Icmentioning

confidence: 99%

Stimulus-specific adaptation in the inferior colliculus: The role of excitatory, inhibitory and modulatory inputs

Ayala

Pérez-González

Malmierca

2016

Biological Psychology

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Patients suffering from pathologies such as schizophrenia, depression or dementia exhibit cognitive impairments, some of which can be reflected in event-related potential (ERP) measurements as the mismatch negativity (MMN). The MMN is one of the most commonly used ERPs and provides an electrophysiological index of auditory change or deviance detection. Moreover, MMN has been positioned as a potentially promising biomarker candidate for the diagnosis and prediction of the outcome of schizophrenia. Dysfunction of neural receptors has been linked to the etiopathology of schizophrenia or the induction of psychophysiological anomalies similar to those observed in schizophrenia. Stimulus-specific adaptation (SSA) is a neural mechanism that contributes to the upstream processing of auditory change detection. Auditory neurons that exhibit SSA specifically adapt their response to repetitive sounds but maintain their excitability to respond to rare ones. Thus, by studying the role of neuronal receptors on SSA, we can contribute to detangle the cellular bases of the impairments in deviance processing occurring in mental pathologies. Here, we review the current knowledge on the effect of GABAA-mediated inhibition and the modulation of acetylcholine on SSA in the inferior colliculus, and we add unpublished original data obtained blocking glutamate receptors. We found that the blockade of GABAA and glutamate receptors mediates an overall increase or decrease of the neural response, respectively, while acetylcholine affects only the response to the repetitive sounds. These results demonstrate that GABAergic, glutamatergic and cholinergic receptors play different and complementary roles on shaping SSA.

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Dose-related effects of memantine on a mismatch negativity-like response in anesthetized rats

Cited by 56 publications

References 29 publications

A Neuronal Model of Predictive Coding Accounting for the Mismatch Negativity

A Neuronal Model of Predictive Coding Accounting for the Mismatch Negativity

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

Stimulus-specific adaptation in the inferior colliculus: The role of excitatory, inhibitory and modulatory inputs

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