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The Picower Institute Spring 2023 Symposium "Environmental and Social Determinants of Child Mental Health
Studies show that abuse, neglect or trauma during childhood can lead to lifelong struggles including with mental health. Fortunately research also indicates that solutions and interventions at various stages of life can be developed to help. But even among people who remain resilient or do not experience acute stresses, a lack of opportunity early in life due to poverty or systemic racism can still constrain their ability to realize their full potential. In what ways are health and other outcomes affected by early life difficulty? What can individuals and institutions do to enhance opportunity?" "This daylong event will feature talks by neuroscientists, policy experts, physicians, educators and activists as they discuss how our experiences and biology work together to affect how our minds develop and what can be accomplished in helping people overcome early disadvantages.
Neural epigenetic mechanisms of early life exercise interventions
Early life adversity, inflammation, and depression-onset: Results from the Teen Resilience Project
My research focuses broadly on the lifelong health disparities associated with experiences of adversity early in life. In this talk I will present the results of our recently completed Teen Resilience Project, a prospective and longitudinal study of first onset depression during adolescence. First, I will present the results on whether and how inflammatory processes may be shaped by early life adversity. Second, I will present data on the role of stress-induced inflammation in reward-related psychological processes. Finally, I will discuss the biobehavioral predictors of first-onset depression in this sample.
Western diet consumption and memory impairment: what, when, and how?
Habitual consumption of a “Western diet”, containing higher than recommended levels of simple sugars and saturated fatty acids, is associated with cognitive impairments in humans and in various experimental animal models. Emerging findings reveal that the specific mnemonic processes that are disrupted by Western diet consumption are those that rely on the hippocampus, a brain region classically linked with memory control and more recently with the higher-order control of food intake. Our laboratory has established rat models in which excessive consumption of different components of a Western diet during the juvenile and adolescent periods of development yields long-term impairments in hippocampal-dependent memory function without concomitant increases in total caloric intake, body weight, or adiposity. Our ongoing work is investigating alterations in the gut microbiome as a potential underlying neurobiological mechanism linking early life unhealthy dietary factors to adverse neurocognitive outcomes.
Brain and behavioural impacts of early life adversity
Abuse, neglect, and other forms of uncontrollable stress during childhood and early adolescence can lead to adverse outcomes later in life, including especially perturbations in the regulation of mood and emotional states, and specifically anxiety disorders and depression. However, stress experiences vary from one individual to the next, meaning that causal relationships and mechanistic accounts are often difficult to establish in humans. This interdisciplinary talk considers the value of research in experimental animals where stressor experiences can be tightly controlled and detailed investigations of molecular, cellular, and circuit-level mechanisms can be carried out. The talk will focus on the widely used repeated maternal separation procedure in rats where rat offspring are repeatedly separated from maternal care during early postnatal life. This early life stress has remarkably persistent effects on behaviour with a general recognition that maternally-deprived animals are susceptible to depressive-like phenotypes. The validity of this conclusion will be critically appraised with convergent insights from a recent longitudinal study in maternally separated rats involving translational brain imaging, transcriptomics, and behavioural assessment.
The development of hunger
All mammals transition from breastfeeding to independent feeding during the lactation period. In humans and other mammals, this critical transition is important for later in life metabolic control and, consequently, for the development of many chronic conditions. Here, Dr. Dietrich will discuss the work of his lab studying the function of hypothalamic neurons involved in homeostatic control during the transition from breastfeeding to independent feeding. His work illuminates novel properties of hypothalamic neurons in early life, suggesting mechanisms by which early life events shape homeostatic regulation throughout the individual’s lifespan.
The Picower Institute Spring 2021 Symposium: Early Life Stress & Mental Health
Though studies show that abuse, neglect or trauma during childhood can lead to lifelong lifelong struggles including in mental health, research also indicates that solutions and interventions at various stages of life can be developed to help. And while many people manage to remain resilient, a lack of opportunity early in life, including because of poverty and systemic racism, can constrain their ability to realize their full potential. In what ways are health and other outcomes affected? How can systems instead restore opportunity? "The Picower Institute for Learning and Memory's biennial spring symposium, 'Early Life Stress & Mental Health,' will examine these issues. The daylong event will feature talks by neuroscientists, policy experts, physicians, educators and activists as they discuss how our experiences and biology work together to affect how our minds develop and what can be accomplished in helping people overcome early disadvantages.
Gut Feelings: The Microbiota-Gut-Brain Axis Across the Lifespan
The microbiota-gut-brain axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of brain development and behaviour during early life, adolescence & ageing. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or by way of microbial metabolites such as short chain fatty acids. Studies in animal models have shown that the development of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of factors can impact the microbiota in early life including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress as well as host genetics. Recently, the gut microbiota has been implicated in regulating the stress response, and social behaviour. Moreover, fundamental brain processes from adult hippocampal neurogenesis to myelination to microglia activation have been shown to be regulated by the microbiome. Further studies will focus on understanding the mechanisms underlying such brain effects and how they can be exploited by microbiota-targeted interventions including ‘psychobiotics’ and diet
Playing fast and loose with glutamate builds healthy circuits in the developing cortex
The construction of cortical circuits requires the precise formation of connections between excitatory and inhibitory neurons during early development. Multiple factors, including neurotransmitters, neuronal activity, and neuronal-glial interactions, shape how these critical circuits form. Disruptions of these early processes can disrupt circuit formation, leading to epilepsy and other neurodevelopmental disorders. Here, I will describe our work into understanding how prolonged post-natal astrocyte development in the cortex creates a permissive window for glutamate signaling that provides tonic activation of developing interneurons through Grin2D NMDA receptors. Experimental disruption of this pathway results in hyperexcitable cortical circuits and human mutations in the Grin2D gene, as well as other related molecules that regulate early life glutamate signaling, are associated with devastating epileptic encephalopathies. We will explore fundamental mechanisms linking early life glutamate signaling and later circuit hyperexcitability, with an emphasis on potential therapeutic interventions aimed at reducing epilepsy and other neurological dysfunction.
Nature, nurture and synaptic adhesion in between
Exposure to proper environment during early development is essential for brain maturation. Impaired sensory input or abnormal experiences can have long-term negative consequences on brain health. We seek to define the precise synaptic aberrations caused by abnormal visual experiences early in life, and how these can be remedied through viral, genetic and environmental approaches. Resulting knowledge will contribute to the development of new approaches to mitigate nervous system damage caused by abnormal early life experience.
Is there universality in biology?
It is sometimes said that there are two reasons why physics is so successful as a science. One is that it deals with very simple problems. The other is that it attempts to account only for universal aspects of systems at a desired level of description, with lower level phenomena subsumed into a small number of adjustable parameters. It is a widespread belief that this approach seems unlikely to be useful in biology, which is intimidatingly complex, where “everything has an exception”, and where there are a huge number of undetermined parameters. I will try to argue, nonetheless, that there are important, experimentally-testable aspects of biology that exhibit universality, and should be amenable to being tackled from a physics perspective. My suggestion is that this can lead to useful new insights into the existence and universal characteristics of living systems. I will try to justify this point of view by contrasting the goals and practices of the field of condensed matter physics with materials science, and then by extension, the goals and practices of the newly emerging field of “Physics of Living Systems” with biology. Specific biological examples that I will discuss include the following: Universal patterns of gene expression in cell biology Universal scaling laws in ecosystems, including the species-area law, Kleiber’s law, Paradox of the Plankton Universality of the genetic code Universality of thermodynamic utilization in microbial communities Universal scaling laws in the tree of life The question of what can be learned from studying universal phenomena in biology will also be discussed. Universal phenomena, by their very nature, shed little light on detailed microscopic levels of description. Yet there is no point in seeking idiosyncratic mechanistic explanations for phenomena whose explanation is found in rather general principles, such as the central limit theorem, that every microscopic mechanism is constrained to obey. Thus, physical perspectives may be better suited to answering certain questions such as universality than traditional biological perspectives. Concomitantly, it must be recognized that the identification and understanding of universal phenomena may not be a good answer to questions that have traditionally occupied biological scientists. Lastly, I plan to talk about what is perhaps the central question of universality in biology: why does the phenomenon of life occur at all? Is it an inevitable consequence of the laws of physics or some special geochemical accident? What methodology could even begin to answer this question? I will try to explain why traditional approaches to biology do not aim to answer this question, by comparing with our understanding of superconductivity as a physical phenomenon, and with the theory of universal computation. References Nigel Goldenfeld, Tommaso Biancalani, Farshid Jafarpour. Universal biology and the statistical mechanics of early life. Phil. Trans. R. Soc. A 375, 20160341 (14 pages) (2017). Nigel Goldenfeld and Carl R. Woese. Life is Physics: evolution as a collective phenomenon far from equilibrium. Ann. Rev. Cond. Matt. Phys. 2, 375-399 (2011).