Disrupted Sleep and Circadian Rhythms in Schizophrenia and Their Interaction With Dopamine Signaling

Ashton, Anna; Jagannath, Aarti

doi:10.3389/fnins.2020.00636

Cited by 56 publications

(35 citation statements)

References 145 publications

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“…Consistently, the severity of symptom expression in ASD and schizophrenia scaled to the degree of impairment in the generation of gamma band oscillation (Edgar et al, 2015; Grent-’t-Jong et al, 2018). Furthermore, ASD and schizophrenia are commonly associated with disturbances in the sleep-wake cycle (Ashton and Jagannath, 2020; Ballester et al, 2020), of which transitions in sleep states may require modulation of electrical synapses in the reticular thalamus by chemical synaptic transmission (Coulon and Landisman, 2017). The foregoing indicates that agents which upregulate electrical synaptic transmission (Urbano et al, 2007; Beck et al, 2008) may benefit individuals with syndromes due to Shank3 mutations.…”

Section: Discussionmentioning

confidence: 99%

Shank3mutations impair electrical synapse scaffolding and transmission in mouse brain

Lautz¹,

Zhu²,

He³

et al. 2021

Preprint

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Shank3 mutations contribute to intellectual disability. Because SHANK3 is a protein scaffold that helps organize the multiprotein network of the glutamatergic postsynaptic density (PSD), alterations in chemical synaptic transmission are implicated. Electrical synaptic transmission is a second form of synaptic transmission, enabled by intercellular channels comprised of connexin36 that support direct electrical communication among neurons, electrical brain rhythms, and neurocognitive states. Using multiplex proteomics, we report that two autism-related mutations of mouse Shank3 disrupt the glutamatergic PSD differently, but have in common the disruption of an association between NMDA-type glutamate-receptors (NMDARs) and connexin36. Mutation of Shank3 exons 13-16 most robustly dissociated connexin36 from NMDARs while impairing electrical synaptic transmission and the synchrony of an electrical rhythm in mouse inferior olive. We suggest that electrical synapses are a component of an "extended PSD" sensitive to Shank3 mutations that produce intellectual disability, at least in part, by impairing electrical synaptic transmission.

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Section: Discussionmentioning

confidence: 99%

Shank3mutations impair electrical synapse scaffolding and transmission in mouse brain

Lautz¹,

Zhu²,

He³

et al. 2021

Preprint

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“…Findings from schizophrenia are very relevant to delusional disorders because of the considerable overlap between the two disorders. In schizophrenia, sleep quality has been correlated with the degree of paranoid ideation [ 36 ], with hostility and violence [ 37 ], with poor quality of life [ 38 , 39 ], with memory functions [ 40 ], with physical activity [ 41 ], and with dopamine signaling [ 42 ]. These correlations may well also apply to DD.…”

Section: Sleep and Psychosismentioning

confidence: 99%

“…Furthermore, the longer the sleep deprivation, the more detrimental its effect. The speculation is that disrupted dopamine pathways serve as the link between sleep and psychotic manifestations [ 42 ].…”

Section: Association Of Sleep Disturbances With Common Symptoms Ofmentioning

confidence: 99%

“…Patients with DD receive the same antipsychotic treatment as patients with schizophrenia, with doses usually being similar [ 78 ]. Due to the fact that sleep and wakefulness are partly controlled by dopamine [ 79 ], a putative link exists between sleep disturbance and AP treatment, although sleep problems in psychiatric illness frequently occur in the absence of any drug treatment [ 42 ]. Table 3 summarizes some of the sleep conditions that have reportedly been aggravated by antipsychotics.…”

Section: Association Of Psychosis Treatment With Sleep Disturbancementioning

confidence: 99%

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Sleep Disturbances in Patients with Persistent Delusions: Prevalence, Clinical Associations, and Therapeutic Strategies

2020

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Sleep disturbances accompany almost all mental illnesses, either because sound sleep and mental well-being share similar requisites, or because mental problems lead to sleep problems, or vice versa. The aim of this narrative review was to examine sleep in patients with delusions, particularly in those diagnosed with delusional disorder. We did this in sequence, first for psychiatric illness in general, then for psychotic illnesses where delusions are prevalent symptoms, and then for delusional disorder. The review also looked at the effect on sleep parameters of individual symptoms commonly seen in delusional disorder (paranoia, cognitive distortions, suicidal thoughts) and searched the evidence base for indications of antipsychotic drug effects on sleep. It subsequently evaluated the influence of sleep therapies on psychotic symptoms, particularly delusions. The review’s findings are clinically important. Delusional symptoms and sleep quality influence one another reciprocally. Effective treatment of sleep problems is of potential benefit to patients with persistent delusions, but may be difficult to implement in the absence of an established therapeutic relationship and an appropriate pharmacologic regimen. As one symptom can aggravate another, comorbidities in patients with serious mental illness all need to be treated, a task that requires close liaison among medical specialties.

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“…At the same time, DA in turn affects the circadian system by controlling the expression of a clock protein PER2 via striatal D2R (Hood et al, 2010). In schizophrenia, there is a bidirectional relationship between the DA system and circadian rhythm, and perturbation to one system can cause disruption in the other system (Ashton and Jagannath, 2020). A recent study in mice found that a mutated Clock gene increased firing rate in VTA DA neurons during daytime when mice are inactive, which led to manic-like behavior (Sidor et al, 2015).…”

Section: Subthreshold Membrane Activity and Circadian Rhythmmentioning

confidence: 99%

Exploring the in vivo subthreshold membrane activity of phasic firing in midbrain dopamine neurons

Otomo¹

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Dopamine is a key neurotransmitter that serves several essential functions in daily behaviors such as locomotion, motivation, stimulus coding, and learning. Disrupted dopamine circuits can result in altered functions of these behaviors which can lead to motor and psychiatric symptoms and diseases. In the central nervous system, dopamine is primarily released by dopamine neurons located in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) within the midbrain, where they signal behaviorally-relevant information to downstream structures by altering their firing patterns. Their “pacemaker” firing maintains baseline dopamine levels at projection sites, whereas phasic “burst” firing transiently elevates dopamine concentrations. Firing activity of dopamine neurons projecting to different brain regions controls the activation of distinct dopamine pathways and circuits. Therefore, characterization of how distinct firing patterns are generated in dopamine neuron populations will be necessary to further advance our understanding of dopamine circuits that encode environmental information and facilitate a behavior. However, there is currently a large gap in the knowledge of biophysical mechanisms of phasic firing in dopamine neurons, as spontaneous burst firing is only observed in the intact brain, where access to intrinsic neuronal activity remains a challenge. So far, a series of highly-influential studies published in the 1980s by Grace and Bunney is the only available source of information on the intrinsic activity of midbrain dopamine neurons in vivo, in which sharp electrodes were used to penetrate dopamine neurons to record their intracellular activity. A novel approach is thus needed to fill in the gap. In vivo whole-cell patch-clamp method is a tool that enables access to a neuron’s intrinsic activity and subthreshold membrane potential dynamics in the intact brain. It has been used to record from neurons in superficial brain regions such as the cortex and hippocampus, and more recently in deeper regions such as the amygdala and brainstem, but has not yet been performed on midbrain dopamine neurons. Thus, the deep brain in vivo patch-clamp recording method was established in the lab in an attempt to investigate the subthreshold membrane potential dynamics of tonic and phasic firing in dopamine neurons in vivo. The use of this method allowed the first in-depth examination of burst firing and its subthreshold membrane potential activity of in vivo midbrain dopamine neurons, which illuminated that firing activity and subthreshold membrane activity of dopamine neurons are very closely related. Furthermore, systematic characterization of subthreshold membrane patterns revealed that tonic and phasic firing patterns of in vivo dopamine neurons can be classified based on three distinct subthreshold membrane signatures: 1) tonic firing, characterized by stable, non-fluctuating subthreshold membrane potentials; 2) rebound bursting, characterized by prominent hyperpolarizations that initiate bursting; and 3) plateau bursting, characterized by transient, depolarized plateaus on which bursting terminates. The results thus demonstrated that different types of phasic firing are driven by distinct patterns of subthreshold membrane activity, which may potentially signal distinct types of information. Taken together, the deep brain in vivo patch-clamp technique can be used for the investigation of firing mechanisms of dopamine neurons in the intact brain and will help address open questions in the dopamine field, particularly regarding the biophysical mechanisms of burst firing in dopamine neurons that control behavior.

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Disrupted Sleep and Circadian Rhythms in Schizophrenia and Their Interaction With Dopamine Signaling

Cited by 56 publications

References 145 publications

Shank3mutations impair electrical synapse scaffolding and transmission in mouse brain

Shank3mutations impair electrical synapse scaffolding and transmission in mouse brain

Sleep Disturbances in Patients with Persistent Delusions: Prevalence, Clinical Associations, and Therapeutic Strategies

Exploring the in vivo subthreshold membrane activity of phasic firing in midbrain dopamine neurons

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