Hallucinating mice and dopamine – towards mechanistic treatment targets for psychosis
Psychotic disorders are devastating conditions without any mechanistic treatment available. One major hurdle in the biological study of psychosis is the challenge of rigorously probing this condition in pre-clinical animal models. The goal of our research is to develop and exploit innovative frameworks for the study of psychosis in mice. In our present work, where we developed a cross-species computational psychiatry approach to probe hallucination-like perception. This enabled us to directly relate human and mouse behavior, and to demonstrate and dissect the causal role of striatal dopamine in hallucination-like perception. Our results suggest a neural circuit mechanism for the long-standing dopamine hypothesis of psychosis, and provide a new translational framework for the biological study of psychosis. This opens up exciting possibilities for advancing the biological understanding of psychosis and to identify mechanistic treatment targets.
The structure of behavior entrained to long intervals
Interpretation of interval timing data generated from animal models is complicated by ostensible motivational effects which arise from the delay-to-reward imposed by interval timing tasks, as well as overlap between timed and non-timed responses. These factors become increasingly prevalent at longer intervals. To address these concerns, two adjustments to long interval timing tasks are proposed. First, subjects should be afforded with reinforced non-timing behaviors concurrent with timing. Second, subjects should initiate the onset of timed stimuli. Under these conditions, interference by extraneous behavior would be detected in the rate of concurrent non- timing behaviors, and changes in motivation would be detected in the rate at which timed stimuli are initiated. In a task with these characteristics, rats initiated a concurrent fixed-interval (FI) random-ratio (RR) schedule of reinforcement. This design facilitated response-initiated timing behavior, even at increasingly long delays. Pre-feeding manipulations revealed an effect on the number of initiated trials, but not on the timing peak function.
Promises and pitfalls in going from the bench to the bedside in autism spectrum disorder
CURE-ND Neurotechnology Workshop - Innovative models of neurodegenerative diseases
One of the major roadblocks to medical progress in the field of neurodegeneration is the absence of animal models that fully recapitulate features of the human diseases. Unprecedented opportunities to tackle this challenge are emerging e.g. from genome engineering and stem cell technologies, and there are intense efforts to develop models with a high translational value. Simultaneously, single-cell, multi-omics and optogenetics technologies now allow longitudinal, molecular and functional analysis of human disease processes in these models at high resolution. During this workshop, 12 experts will present recent progress in the field and discuss: - What are the most advanced disease models available to date? - Which aspects of the human disease do these accurately models, which ones do they fail to replicate? - How should models be validated? Against which reference, which standards? - What are currently the best methods to analyse these models? - What is the field still missing in terms of modelling, and of technologies to analyse disease models? CURE-ND stands for 'Catalysing a United Response in Europe to Neurodegenerative Diseases'. It is a new alliance between the German Center for Neurodegenerative Diseases (DZNE), the Paris Brain Institute (ICM), Mission Lucidity (ML, a partnership between imec, KU Leuven, UZ Leuven and VIB in Belgium) and the UK Dementia Research Institute (UK DRI). Together, these partners embrace a joint effort to accelerate the pace of scientific discovery and nurture breakthroughs in the field of neurodegenerative diseases. This Neurotechnology Workshop is the first in a series of joint events aiming at exchanging expertise, promoting scientific collaboration and building a strong community of neurodegeneration researchers in Europe and beyond.
The BHP Chronic Pain Health Integration Team: Helping those with chronic pain to access the support they need / A bit of a To and Fro with population pain science
Candy will provide an overview of Bristol Health Partners' Chronic Pain Health Integration Team which brings together clinicians, academics, patients and carers to focus on improving the lives of those with chronic pain and supporting those who provide chronic pain services or care. Tony will describe recent and ongoing studies that have been forward and reverse translating pain neuroscience from animal to human including functional imaging in patients, microneurography, industrial partnerships and trials of novel preventative approaches that are benefitting from the people, expertise and facilities available in Bristol and GW4.
Using marmosets for the study of the visual cortex: unique opportunities, and some pitfalls
Marmosets (Callithrix jacchus) are small South American monkeys which are being increasingly becoming adopted as animal models in neuroscience. Knowledge about the marmoset visual system has developed rapidly over the last decade. But what are the comparative advantages, and disadvantages involved in adopting this emerging model, as opposed to the more traditionally used macaque monkey? In this talk I will present case studies where the simpler brain morphology and short developmental cycle of the marmoset have been key factors in facilitating discoveries about the anatomy and physiology of the visual system. Although no single species provides the “ideal” animal model for invasive studies of the neural bases of visual processing, I argue that the development of robust methodologies for the study of the marmoset brain provides exciting opportunities to address long-standing problems in neuroscience.
Following neuronal trajectories
Malformations of the human cerebral cortex represent a major cause of developmental disabilities. To date, animal models carrying mutations of genes so far identified in human patients with brain malformations only partially recapitulate the expected phenotypes and therefore do not provide reliable models to entirely understand the molecular and cellular mechanisms responsible for these disorders. Hence, we combine the in vivo mouse model and the human brain organoids in order to better comprehend the mechanisms involved in the migration of neurons during human development and tackle the causes of neurodevelopmental disorders. Our results show that we can model human brain development and disorders using human brain organoids and contribute to open new avenues to bridge the gap of knowledge between human brain malformations and existing animal models.