Topic: clozapine-N-oxide

Clinical studies in PRISM1 (Psychiatric Ratings using Intermediate Stratified Markers) indicated that social dysfunction is transdiagnostically associated with default mode network dysconnectivity. Low social functioning groups exhibit decreased DTI fractional anisotropy in backbone structures of the DMN such as forceps minor, the interhemispheric connection of the orbitofrontal cortices (OFC). This study aims to back-translate these data by understanding the role of parvalbumin interneurons (PV+) in OFC.We studied the effect PV+ interneuron activation on social behaviors in mice by using an a

Sleep and wakefulness are controlled by specific brain regions. These regions have been identified by classical elimination of brain regions or by acute manipulation of neural activity. However, acute manipulation of these regions often has only a temporary effect on the sleep-wake cycles and chronic inhibition of neural activity in these areas has little effect. These may have been an adaptation and compensation by other brain regions. The preoptic area (POA) has long been recognized as the sleep center first proposed by von Economo. However, a recent optogenetic study found that photostimula

Electrical activity plays a crucial role in the development of neurons and the formation of neuronal networks. Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools that can control the activity of neurons at the single-cell level by activating specific G protein signaling. In this study, we aimed to investigate whether the excitatory hM3Dq receptor is sufficient to influence the growth of dendrites and axons in cortical neurons. When activated, Gq-coupled hM3Dq leads to depolarization by increasing intracellular calcium levels. We biolistically transfecte

In Parkinson’s disease, nigrostriatal degeneration is associated with striatal astrocytes activation. However, the possible causal relationships between striatal astrocytosis and nigrostriatal degeneration remain unclear. Our central hypothesis is that corticostriatal alterations may act as a top-down stressor for retrograde nigrostriatal neurodegeneration (Foffani and Obeso, Neuron 2018). Here we tested whether chronically increasing corticostriatal activity and/or overexpressing corticostriatal alpha-synuclein may induce striatal astrocytosis in mice.Glutamatergic corticostriatal neurons in

Sleep is present throughout the animal kingdom, but its function remains to be fully determined. Rapid eye movement sleep (REM) is characterised by muscle atonia, heightened theta oscillations, and the occurrence of ponto-geniculo-occipital (PGO) waves or P-waves. The pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT) have been implicated in REM sleep generation, and their cholinergic neuronal activity was specifically associated with P-waves. However, the precise role of pontine cholinergic neurons in REM sleep remains elusive, particularly their impact on sleep architecture and P-w

Posttraumatic stress disorder (PTSD), a psychopathological condition triggered by traumatic events, affects the brain's energy demand. The median prefrontal cortex (m-PFC) plays a crucial role in regulating the fear response. Moreover, it contains glucose-sensing glucose transporter 2 (GLUT2)-containing neurons. Therefore, we hypothesized that manipulation of these mPFC-GLUT2 cells could impact the behavioral outcome.An adeno-associated viral vector was used to deliver a stimulatory DREADD sequence into the mPFC of mice from both sexes. The infected cells were stimulated by clozapine-N-oxide r

Although rehabilitative training of forced limb use (FLU) after intracerebral hemorrhagic stroke (ICH) results in forelimb functional recovery in rats, it is still unknown whether quality change of skilled reaching is induced by FLU after ICH. To analyze detail kinematics of the forelimb function, markerless pose estimation using DeepLabCut based on deep neural network was applied to ICH model rats that can be selectively inhibited in the regulatory system of motor function.To inhibit the regulatory system after functional recovery, the cerebello-rubral tract is selectively blocked with DREADD

Hypoxia-ischemia (HI) is a significant cause of disability and mortality in neonates. HI is characterized by acute energetic failure and secondary inflammatory response. The primary therapeutic intervention is hypothermia, which presents limited neuroprotective effects. Environmental approaches, such as skin-to-skin contact, have been highlighted for their benefits in brain development. Oxytocin (OT) is a neuropeptide with roles in parturition and social behavior, but it also modulates the microglial inflammatory responses. Therefore, the study of OT signaling can be helpful to bridge the gap

Neurons in the centromedial amygdala (CeM) are activated during fear memory formation. We designed a new viral vector, AAV9-pfos-hM4Di:mCherry:PEST expressing Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) under a c-fos promoter, enabling the specific manipulation of activated neurons. We use this viral vector to temporarily inactivate the neurons involved during cued-fear learning in the CeM and to uncover their molecular profile.Male and female wildtype C57BL/6J mice are injected with the viral vector in the CeM, exposing one group to the shocks paired with the tones (f