Mice with subtle reduction of NMDA NR1 receptor subunit expression have a selective decrease in mismatch negativity: Implications for schizophrenia prodromal population

Featherstone, Robert E.; Shin, Rick; Kogan, Jeffrey H.; Liang, Yuling; Matsumoto, Mitsuyuki; Siegel, Steven J.

doi:10.1016/j.nbd.2014.10.010

Cited by 55 publications

(34 citation statements)

References 68 publications

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“…While alterations in broadband spectral power at baseline have been reported in ketamine models in rodents (Kocsis et al, 2013), such increases are inconsistent across other pharmacological and genetic models of SZ (Featherstone et al, 2015; Sullivan et al, 2015), and similar observations, as well as changes in relative theta power, in SZ are present but variable (Clementz et al, 1994; Hamm et al, 2014; Hirano et al, 2015). In general, dysregulation of gamma-band dynamics and signal to noise ratio, rather than a simple increase or decrease, is a more consistent finding in SZ (Moran and Hong, 2011) and both models recapitulate this deficit in a primary sensory cortex.…”

Section: Resultsmentioning

confidence: 96%

Altered Cortical Ensembles in Mouse Models of Schizophrenia

Hamm

Peterka

Gogos

et al. 2017

Neuron

160

161

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Summary In schizophrenia, brain-wide alterations have been identified at the molecular and cellular levels, yet how these phenomena affect cortical circuit activity remains unclear. We studied two mouse models of schizophrenia-relevant disease processes: chronic ketamine administration (KET) and Df(16)A+/−, modeling 22q11.2 microdeletions, a genetic variant highly penetrant for schizophrenia. Local field potential recordings in visual cortex confirmed gamma-band abnormalities similar to patient studies. Two-photon calcium imaging of local cortical populations revealed in both models a deficit in the reliability of neuronal coactivity patterns (ensembles) which was not a simple consequence of altered single neuron activity. This effect was present in ongoing and sensory evoked activity and was not replicated by acute ketamine administration or pharmacogenetic parvalbumin-interneuron suppression. These results are consistent with the hypothesis that schizophrenia is an “attractor” disease and demonstrate that degraded neuronal ensembles are a common consequence of diverse genetic, cellular, and synaptic alterations seen in chronic schizophrenia.

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Section: Resultsmentioning

confidence: 96%

Altered Cortical Ensembles in Mouse Models of Schizophrenia

Hamm

Peterka

Gogos

et al. 2017

Neuron

160

161

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“…But animal studies are controversial. While Farley, Quirk, Doherty, and Christian (2010) found that SSA in auditory cortical neurons of rats was insensitive to the systemic application of NMDA antagonists, Featherstone et al (2014), using a probably more sensitive murine model with a heterozygous alteration of the NMDA receptor NR1 subunit gene, reported a significant reduction in the expression of NMDA receptors that caused a distinct decrement of MMN. The discrepancy of the effects of NMDA receptors on MMN and SSA is intriguing.…”

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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“…Studies employing basic oddball paradigms have shown that MMN-like waveforms (deviant minus redundant) are present in mouse EEG recordings (Featherstone et al, 2015), but an analytical and mechanistic differentiation of higher order deviance processing from basic sensory adaptation (SSA) is absent, leaving the translational relevance to human MMN unclear (Harms et al, 2015). Some recent studies focusing on SSA have made use of mouse strains allowing interneuron access with optogenetics or florescent microscopy (PV-cre, SOM-cre).…”

mentioning

confidence: 99%

Somatostatin Interneurons Control a Key Component of Mismatch Negativity in Mouse Visual Cortex

2016

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Summary Patients with schizophrenia have deficient sensory processing, undermining how they perceive and relate to a changing environment. This impairment can be captured by the reduced “mismatch negativity” index (MMN), an electroencephalographic biomarker of psychosis. The biological factors contributing to MMN are unclear, though mouse research, where genetic and optical methods could be applied, has given some insight. Using fast two-photon calcium imaging and multielectrode recordings in awake mice, we find that visual cortical circuits display i) adapted (decreased) responses to repeated stimuli and ii) amplified responses to a deviant stimulus, the key component of human MMN. Moreover, pharmacogenetic silencing of somatostatin-containing interneurons specifically eliminated this amplification along with its associated theta/alpha band response, leaving stimulus specific adaption and related gamma-band modulations intact. Our results validate a mouse model of MMN and suggest that abnormalities in somatostatin-containing interneurons cause sensory deficits underlying MMN and schizophrenia.

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Mice with subtle reduction of NMDA NR1 receptor subunit expression have a selective decrease in mismatch negativity: Implications for schizophrenia prodromal population

Cited by 55 publications

References 68 publications

Altered Cortical Ensembles in Mouse Models of Schizophrenia

Altered Cortical Ensembles in Mouse Models of Schizophrenia

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

Somatostatin Interneurons Control a Key Component of Mismatch Negativity in Mouse Visual Cortex

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