Amphetamine alters an EEG marker of reward processing in humans and mice

Cavanagh, James F.; Olguin, Sarah L.; Talledo, Jo; Kotz, J; Roberts, Benjamin Z; Nungaray, John; Sprock, Joyce; Gregg, David; Bhakta, Savita; Light, Gregory A.; Swerdlow, Neal R.; Young, Jared W.; Brigman, Jonathan L.

doi:10.1007/s00213-022-06082-z

Cited by 26 publications

(21 citation statements)

References 51 publications

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“…4f-j). These tf-ROI power analyses are consistent with previously reported event-responsive power changes 53 . Importantly, they indicate reduction of circHomer1 within the OFC induces reward-and error-related neural alterations during chance reversal, the stage where behavior is signi cantly impaired in circHomer1 KD animals.…”

Section: Itpc Is Aberrantly Increased Across Reversal Learning Follow...supporting

confidence: 91%

“…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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Section: Itpc Is Aberrantly Increased Across Reversal Learning Follow...supporting

confidence: 91%

Section: Local Eld Potential Analysis Of Power and Phase Consistencymentioning

confidence: 99%

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

Zimmerman¹,

Weick²,

Papageorgiou³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Reduction of tf-ROI power relative to baseline was observed following incorrect choices consistent with previous work measuring punishment-associated power changes in rodents and humans [64] (Fig. 4I-P).…”

Section: Kd Of Circhomer1 In the Ofc Of Mice During A Visual Discrimi...supporting

confidence: 90%

“…4B black boxes) and punishmentrelated (500-800ms) (Fig. 4J black boxes) signaling as described previously [64]. No signi cant group differences were observed across time-frequency ROIs (tf-ROIs) on the rst day of reversal (Fig.…”

Section: Kd Of Circhomer1 In the Ofc Of Mice During A Visual Discrimi...supporting

confidence: 52%

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

Zimmerman¹,

Weick²,

Papageorgiou³

et al. 2022

Preprint

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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“…The most important feature of depression is the absence of joyful emotions. Dopamine (DA) has become a synonym for joy and reward [ 17 ], thus increasing DA might be a good way for treating MDD [ 18 , 19 ], and, indeed, the US FDA (food and drug agency) recently approved ketamine as a drug capable of rapid antidepressant function in 2019 [ 20 , 21 ]. Ketamine itself is a drug and a stimulant, and one of its main functions is to increase release of dopamine.…”

Section: Monoamine Neurotransmitters Mediate Three Core Effectsmentioning

confidence: 99%

Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders

Jiang

Zou

et al. 2022

Pharmaceuticals

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Major depressive disorder (MDD) is a common and complex mental disorder, that adversely impacts an individual’s quality of life, but its diagnosis and treatment are not accurately executed and a symptom-based approach is utilized in most cases, due to the lack of precise knowledge regarding the pathophysiology. So far, the first-line treatments are still based on monoamine neurotransmitters. Even though there is a lot of progress in this field, the mechanisms seem to get more and more confusing, and the treatment is also getting more and more controversial. In this study, we try to review the broad advances of monoamine neurotransmitters in the field of MDD, and update its effects in many advanced neuroscience studies. We still propose the monoamine hypothesis but paid special attention to their effects on the new pathways for MDD, such as inflammation, oxidative stress, neurotrophins, and neurogenesis, especially in the glial cells, which have recently been found to play an important role in many neurodegenerative disorders, including MDD. In addition, we will extend the monoamine hypothesis to basic emotions; as suggested in our previous reports, the three monoamine neurotransmitters play different roles in emotions: dopamine—joy, norepinephrine—fear (anger), serotonins—disgust (sadness). Above all, this paper tries to give a full picture of the relationship between the MDD and the monoamine neurotransmitters such as DA, NE, and 5-HT, as well as their contributions to the Three Primary Color Model of Basic Emotions (joy, fear, and disgust). This is done by explaining the contribution of the monoamine from many sides for MDD, such the digestive tract, astrocytes, microglial, and others, and very briefly addressing the potential of monoamine neurotransmitters as a therapeutic approach for MDD patients and also the reasons for its limited clinical efficacy, side effects, and delayed onset of action. We hope this review might offer new pharmacological management of MDD.

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Amphetamine alters an EEG marker of reward processing in humans and mice

Cited by 26 publications

References 51 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

Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders

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