Electrophysiological biomarkers of behavioral dimensions from cross-species paradigms

Cavanagh, James F.; Gregg, David; Light, Gregory A.; Olguin, Sarah L.; Sharp, Richard F.; Bismark, Andrew W.; Bhakta, Savita; Swerdlow, Neal R.; Brigman, Jonathan L.; Young, Jared W.

doi:10.1038/s41398-021-01562-w

Cited by 29 publications

(11 citation statements)

References 81 publications

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“…Dysfunction of this region is commonly found in individuals with psychiatric phenotypes including BD and SCZ and is believed to underlie some of the detrimental behaviors associated with poor decision-making in these populations 46,47 .Recent work has uncovered electrophysiological signatures that correlate with neural dysfunction in patients with SCZ and BD 48 . Importantly, similar signatures have been found in animal modeling of traits seen in these disorders including psychosis and cognitive dysfunction 49,50 . Cognitive-associated electrophysiological signatures are conserved across species 49 and provide a more reliable approach for identifying the underlying cognitive dysfunction compared to behavior alone.…”

supporting

confidence: 61%

“…Recent work has uncovered electrophysiological signatures that correlate with neural dysfunction in patients with SCZ and BD 48 . Importantly, similar signatures have been found in animal modeling of traits seen in these disorders including psychosis and cognitive dysfunction 49,50 . Cognitive-associated electrophysiological signatures are conserved across species 49 and provide a more reliable approach for identifying the underlying cognitive dysfunction compared to behavior alone.…”

supporting

confidence: 61%

“…Difference in power was analyzed by comparing circHomer1 KD to control-injected animals. Time-frequency regions of interest (tf-ROI) were analyzed as described previously 49,53 . For ITPC ROIs, choice-related phase consistency was analyzed in the 0-250ms window directly following a correct or incorrect choice.…”

Section: Local Eld Potential Analysis Of Power and Phase Consistencymentioning

confidence: 99%

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Knockdown of circHomer1 in the orbitofrontal cortex results in differential encoding of salient stimuli

Zimmerman¹,

Weick²,

Papageorgiou³

et al. 2022

Preprint

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Identifying genetic factors that influence electrophysiological signatures associated with disordered behavior will reveal mechanisms of cognitive dysfunction relevant to disease. Homer1 is a reproducible gene candidate for synaptic and cognitive function. Alternative splicing produces activity-dependent isoforms including the circular RNA, circHomer1. While dysregulation of circHomer1 expression has been identified across multiple psychiatric and neurodegenerative disorders and is associated with impaired cognitive flexibility, it is unknown whether circHomer1 can induce electrophysiological signatures relevant to cognitive dysfunction in these disorders. Using in vivo microarray recordings within the orbitofrontal cortex (OFC) of awake, behaving mice during a translational touchscreen task, we demonstrate that reduction of circHomer1 within the OFC induces robust changes in multiunit firing rate and local field potential (LFP) coordination and power to salient stimuli. Further, these electrophysiological changes are associated with transcriptional downregulation of glutamatergic signaling effectors and behavioral alterations leading to impaired cognitive flexibility.

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supporting

confidence: 61%

supporting

confidence: 61%

Section: Local Eld Potential Analysis Of Power and Phase Consistencymentioning

confidence: 99%

See 1 more Smart Citation

Knockdown of circHomer1 in the orbitofrontal cortex results in differential encoding of salient stimuli

Zimmerman¹,

Weick²,

Papageorgiou³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent work has uncovered electrophysiological signatures that correlate with neural dysfunction in patients with SCZ and BD [52,53]. Importantly, similar signatures have been found in animal modeling of traits seen in these disorders including psychosis and cognitive dysfunction [54,55]. Cognitive-associated electrophysiological signatures are conserved across species [53,54] and provide a more reliable approach for identifying the underlying cognitive dysfunction compared to behavior alone.…”

Section: Introductionmentioning

confidence: 73%

Knockdown of circHomer1 in the orbitofrontal cortex results in differential encoding of salient stimuli

Zimmerman¹,

Weick²,

Papageorgiou³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

BackgroundCircHomer1 is an activity-dependent circular RNA (circRNA) isoform produced from back-splicing of the Homer1 transcript. Homer1 isoforms are well-known regulators of homeostatic synaptic plasticity through post-synaptic density scaffold regulation. Homer1 polymorphisms have been associated with psychiatric diseases including schizophrenia (SCZ) and bipolar disorder (BD). Postmortem tissue from patients with SCZ and BD showed reduced circHomer1 levels within the orbitofrontal cortex (OFC), a region associated with behavioral flexibility. While dysregulation of circHomer1 expression has recently been identified across multiple psychiatric and neurodegenerative disorders and is associated with impaired behavioral flexibility in mice, it is unknown whether circHomer1 can induce electrophysiological signatures relevant to cognitive dysfunction in these disorders.MethodsCircHomer1 was knocked down in bilateral orbitofrontal cortex of C57BL/6J male mice and in vivo microarray recordings were captured throughout a touchscreen reversal learning task to identify electrophysiological changes associated with reduction of circHomer1. Following task completion, qRT-PCR was used to quantify transcriptional changes following circHomer1 knockdown.ResultsKnockdown of circHomer1 within the OFC induced robust changes in multiunit firing rate and local field potential coordination and power to salient stimuli during reversal learning. Further, these electrophysiological changes were associated with transcriptional downregulation of glutamatergic signaling effectors and behavioral alterations leading to impaired cognitive flexibility.ConclusionsCircHomer1 is a stable biomolecule, whose knockdown in rodent OFC produces lasting electrophysiological and transcriptional changes important for efficient reversal learning. This is, to our knowledge, the first demonstration of a psychiatric-associated circRNA contributing to electrophysiological, transcriptional, and behavioral alterations relevant to psychiatric phenotypes.

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“…Given the interspecies [and inter-individual (Haegens et al, 2014)] variation in frequency discussed earlier, we propose that oscillation studies should be grounded in which behavioral conditions, neural circuits, neural subpopulations, or even ion channels (Kalmbach et al, 2018;Stagkourakis et al, 2018), elicit the oscillation. To do so, it will be critical to conduct carefully designed parallel human-murine studies which use equivalent tasks (Cavanagh et al, 2021), identify the human EEG source with sophisticated source localization algorithms (Michel and Brunet, 2019;Seeber et al, 2019) and/or functional imaging, and confirm similar neural population involvement with pharmacology when possible.…”

Section: Introduction Historymentioning

confidence: 99%

Breaking Down a Rhythm: Dissecting the Mechanisms Underlying Task-Related Neural Oscillations

Ibarra-Lecue

Haegens

Harris

2022

Front. Neural Circuits

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A century worth of research has linked multiple cognitive, perceptual and behavioral states to various brain oscillations. However, the mechanistic roles and circuit underpinnings of these oscillations remain an area of active study. In this review, we argue that the advent of optogenetic and related systems neuroscience techniques has shifted the field from correlational to causal observations regarding the role of oscillations in brain function. As a result, studying brain rhythms associated with behavior can provide insight at different levels, such as decoding task-relevant information, mapping relevant circuits or determining key proteins involved in rhythmicity. We summarize recent advances in this field, highlighting the methods that are being used for this purpose, and discussing their relative strengths and limitations. We conclude with promising future approaches that will help unravel the functional role of brain rhythms in orchestrating the repertoire of complex behavior.

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Electrophysiological biomarkers of behavioral dimensions from cross-species paradigms

Cited by 29 publications

References 81 publications

Knockdown of circHomer1 in the orbitofrontal cortex results in differential encoding of salient stimuli

Knockdown of circHomer1 in the orbitofrontal cortex results in differential encoding of salient stimuli

Knockdown of circHomer1 in the orbitofrontal cortex results in differential encoding of salient stimuli

Breaking Down a Rhythm: Dissecting the Mechanisms Underlying Task-Related Neural Oscillations

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