The GPe regulates information flow in cortico-basal ganglia-thalamic circuits. This nucleus relays ascending and descending signals and serves as a central hub within the CBGT network. Abstract For decades, the external globus pallidus (GPe) has been viewed as a passive way-station in the indirect pathway of the cortico-basal ganglia-thalamic (CBGT) circuit, sandwiched between striatal inputs and basal ganglia outputs. According to this model, one-way descending striatal signals in the indirect pathway amplify the suppression of downstream thalamic nuclei by inhibiting GPe activity. Here, we ..read more

Abstract The anterior cingulate cortex (ACC) has been shown to be critical to many aspects of executive function including filtering irrelevant information, updating response contingencies when reinforcement contingencies change and stabilizing task sets. Nonspecific lesions to this region in rats produce a vulnerability to distractors that have gained salience through prior associations with reinforcement. These lesions also exacerbate cognitive fatigue in tests of sustained attention but do not produce global attentional impairments nor do they produce distractibility to novel distractors t ..read more

CDKL5 deficiency disorder (CDD) is a genetic disease that produces lifelong neurological dysfunction, including autism, intellectual disability and epilepsy. This study employed a clinically relevant mouse model of CDD to investigate the effects of cannabidiol (CBD) on behavioural outcomes and found that it attenuates seizure susceptibility, memory impairments and social behavioural deficits. The clinical impact of this research is potentially very high, as CBD is already FDA-approved for epilepsy. The study also demonstrates altered signalling related to the endogenous endocannabinoid system ..read more

The hippocampus, a brain structure importantly involved in Alzheimer's disease, is differentially regulated over its longitudinal axis. Across age, the anterior–posterior volume ratio on MRI varies differently in cognitively normal subjects, mild cognitive impairment and Alzheimer's disease. These findings suggest the longitudinal ratio might be a differentiating MRI metric with potential pathophysiological and diagnostic implications. Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects the hippocampus. Since hippocampal studies have highlight ..read more

This study shows that multiple exposures to an object reduce the activity of dopamine–glutamate neurons in the ventral tegmental area, enhancing the mice's ability to discriminate new objects in a subsequent novelty recognition test. Chemogenetic inhibition of dopamine neurons during a single familiarization session paralleled the effects of multiple sessions, improving novelty discrimination. This underscores dopamine neurons' role in modulating the salience of an object's memory during familiarization. Abstract Dopamine neurons signal the salience of environmental stimuli and influence lea ..read more

Nerve stimulation-evoked contraction of muscles from mild MuSK myasthenia gravis mice (injected with low doses patient IgG4) appeared partly insensitive to μ‑Conotoxin-GIIIB. This blocker of NaV1.4 voltage-gated sodium channels normally completely eliminates muscle contraction. We studied neuromuscular transmission and possible compensatory expression of NaV1.5 (cardiac-type) channels but showed this was not the case. Which other Na channel types or related factors are involved remains to be seen. Abstract Muscle-specific kinase myasthenia gravis (MuSK MG) is caused by autoantibodies against ..read more

(A) Striatal astrocytes express the dopamine transporter. (B) Exposure to heroin reduces striatal astrocytic dopamine transporter (DAT) protein and mRNA levels. (C) Heroin-induced alterations in DAT expression levels across striatal territories parallel their functional engagement over the course of the development of incentive heroin seeking habits, including the increased functional coupling between the nucleus accumbens and dorsolateral striatum associated with heroin use disorder. Abstract The emergence of compulsive drug-seeking habits, a hallmark feature of substance use disorder, has ..read more

Chronotype and subjective sleep quality have been linked to white matter alterations in several populations. We tested whether these factors predict white matter integrity in a transdiagnostic sample of youth in the early phases of mental disorders. Using machine learning, we find that chronotype (but not subjective sleep quality) is a top-ranked predictor of white matter integrity in youth with mood disorders, particularly in the corpus callosum and corona radiata. Abstract Protecting brain health is a goal of early intervention. We explored whether sleep quality or chronotype could predict ..read more

Deficiencies of 14-3-3 proteins in the mouse brain lead to molecular, synaptic and behavioural alterations that correlate with phenotypes of neuropsychiatric diseases. Here, we determine that 14-3-3 inhibition in hippocampal pyramidal neurons results in a dramatic increase in intrinsic neuronal excitability. We further identify behaviour-induced changes in action potential duration and firing patterns in 14-3-3 functional knockout mice. This study provides an important link in how 14-3-3 dysfunctions in the hippocampus can cause psychosis-like behaviours. Abstract 14-3-3 proteins are a famil ..read more

Abstract GABAergic neurons represent 10–15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. The largest GABAergic class in the neocortex is represented by the parvalbumin-expressing fast-spiking neurons, which provide powerful somatic inhibition to their postsynaptic targets. Recently, the density of parvalbumin interneurons has been shown to be lower in associative areas of the mouse cortex as compared with sensory and motor areas. Modelling work based on these quantifications linked the low-density of parvalbumin interneurons ..read more