Ongoing neural activity has been observed across several brain regions and is thought to reflect the internal state of the brain. Yet, it is important to understand how ongoing neural activity interacts with sensory experience and shapes sensory representations. Here, we show that the projection neurons of the fruit fly antennal lobe exhibit spatiotemporally organized ongoing activity. After repeated exposure to odors, we observe a gradual and cumulative decrease in the amplitude and number of calcium events occurring in the absence of odor stimulation, as well as a reorganization of correlations between olfactory glomeruli. Accompanying these plastic changes, we find that repeated odor experience decreases trial-to-trial variability and enhances the specificity of odor representations. Our results reveal an odor-experience-dependent modulation of ongoing and sensory-evoked activity at peripheral levels of the fruit fly olfactory system.
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http://dx.doi.org/10.1016/j.celrep.2021.110165 | DOI Listing |
Background: Alzheimer's disease (AD) agitation is a distressing neuropsychiatric symptom characterized by excessive motor activity, verbal aggression, or physical aggression. Agitation is one of the causes of caregiver distress, increased morbidity and mortality, and early institutionalization in patients with AD. Current medications used for the management of agitation have modest efficacy and have substantial side effects.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
EQT Life Sciences Partners, Amsterdam, 1071 DV Amsterdam, Netherlands.
Background: Alzheimer's disease (AD) trials report a high screening failure rate (potentially eligible trial candidates who do not meet inclusion/exclusion criteria during screening) due to multiple factors including stringent eligibility criteria. Here, we report the main reasons for screening failure in the 12-week screening phase of the ongoing evoke (NCT04777396) and evoke+ (NCT04777409) trials of semaglutide in early AD.
Method: Key inclusion criteria were age 55-85 years; mild cognitive impairment due to AD (Clinical Dementia Rating [CDR] global score of 0.
Background: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a neurodegenerative disorder without a cure. Targeting this multifactorial disease by repurposing FDA approved drugs serves as a faster mode of treatment due to its pre-established human safety. We tested terazosin (TZ), an a-1 adrenergic receptor (AR) antagonist and phosphoglycerate kinase-1 (PGK1) activator as having potential to treat AD.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with neuroinflammation and heightened production of reactive oxygen species (ROS) in the brain from overactive NADPH Oxidase 2 (NOX2). The current study examines whether administration of a novel, brain-penetrant NOX2 inhibitor (CPP11G & CPP11H) reduces amyloid plaque load and improves AD-associated vascular dysfunction in a male APP-PS1 mouse model of AD.
Method: Intraperitoneal injections of CPP11G (n = 1) or CPP11H (n = 2) three times per week began at 9-10 months of age in the treatment APP-PS1 group (15 mg/kg).
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