Seminars and events

The insular cortex is a multisensory brain region which is involved in many behaviors, including pain, addiction, social behavior, learning & memory, and feeding/metabolism. To date, the gene expression patterns of the insular cortex have not been systematically studied, but it has generally been assumed to be similar to other cortical areas. However, our data indicates that the insular cortex may have some key transcriptomic differences from other cortical areas, and that these insula-specific genes may have important behavioral functions. To probe this, we conducted single cell sequencing of the insular cortex and compared it to somatosensory cortex. We find that indeed the insular cortex has a distinct transcriptomic makeup compared to somatosensory cortex. We then investigated the function of two insula-specific genes in complex feeding behaviors. Probing the function of these insula-specific cell-types reveals important insights into the functions of the insular cortex vis-a-vis complex motivated behaviors, in particular salience detection and internal state sensing. [more]

It is clear that the cause of obesity is a result of eating more than you burn. What is more complex to answer is why some people eat more than others? Differences in our genetic make-up mean some of us are, for a myriad of different reasons, driven to eat more than others. We now know that the genetics of body-weight, on which obesity sits on one end of the spectrum, is in actuality the genetics of how the brain regulates appetite. In this talk, I will discuss the use of different studies, ranging from large population based cohorts, to smaller consanguineous groups of individuals with extreme phenotypes, coupled with ‘omics technologies, to identify novel genes linked to obesity. [more]

Midbrain dopamine (mDA) neurons are required for the formation of reward-associated memories, a vital mechanism allowing animals to adapt to their environment. On the flipside, dopaminergic dysfunction caused by repeated exposure to strong reinforcers such as drugs of abuse or hyperpalatable foods can potentially trigger addiction and compulsive, ‘binge’-style eating behaviors, respectively. Intriguingly, humans as well as other animals display striking inter-individual differences in their vulnerability to develop such maladaptive behaviors, which can even be observed despite identical genetics and environment. Thus, we here sought out to explore the role of epigenetic modifications as potential drivers of stochastic variation in the susceptibility to develop binge-eating behavior. To accomplish this, we first performed fluorescence-assisted nuclei sorting (FANS) specifically of mDA neurons from control mice versus mice trained to binge-feed on a hyperpalatable, high-fat diet. When analyzing the DNA methylation landscape of this purified cell type by means of the Infinium Mouse Methylation BeadChip (Mm285), we found that binge-feeding induces a dramatic reorganization of the mDA methylome (2,674 DMR with increased methylation versus 9,799 DMR with decreased methylation; p-value 0.05 and effect size 0.1). The marked loss of methyl marks across multiple genomic regions suggests a prominent role of demethylating enzymes such as Ten-Eleven Translocation 1 (TET-1) dioxygenase, which we interestingly found to be highly enriched in mDA neurons. Consistently, Tet1 haploinsufficient mice (Tet1 ^+/-) exhibited marked differences in motivated, reward-related behaviors including reduced sucrose preference and attenuated binge-feeding. Notably, bistable segregation into either binge-prone versus binge-resistant animals was significantly amplified in Tet1^+/- mice hinting at a potential role in the stochasticity of behavioral variation towards calorie rewards. To reverse already established binge-feeding phenotypes, we started leveraging virus-based approaches to rewire the mDA methylome in a locus-specific, temporally controlled and TET1-mediated fashion in-vivo. In sum, we provide evidence for TET1-mediated DNA demethylation in mDA neurons as an important non-genetic, non-environmental regulator determining flexibility in motivated behaviors and susceptibility to binge-eating disorders. [more]

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In this presentation, I will highlight our recent work on small intestinal protein sensing and how the kidney and the brain work in parallel to regulate feeding, weight and glucose homeostasis. Our findings unveil therapeutic targets in the small intestine, kidney and / or the brain to lower weight and glucose levels in obesity and diabetes. [more]

In this talk I will discuss a link between obesity, diet, and brain health, drawing on neuroimaging data from population-based cohorts and interventional trials. Results indicate that a higher body mass index and visceral fat correlate with accelerated brain aging, while interventional data suggest benefits from weight loss and plant-based diets on brain structure and function. In parallel, I like to share exemplary challenges that call for open science and a more holistic approach to study gut-brain interactions. Overall, previous work underlined the intertwined nature of nutrition, metabolism and brain health, advocating for targeted interventions as a means to enhance brain plasticity. [more]

Prof. Dr. Cristina Garcia Caceres is a renowned Spanish neuroscientist known for her groundbreaking research in obesity and neuroendocrinology. She earned her Ph.D. in Madrid, Spain, and pursued academic internships at Yale University, USA, and Göteborg University, Sweden. Following her doctoral studies, she conducted postdoctoral research at Helmholtz Munich and TUM in Germany. In 2015, she established the Astrocyte-Neuron Network Unit at the Institute for Diabetes and Obesity. Currently, she holds the position of W2 professor at LMU and serves as the Head of Research and Deputy Director at the Institute for Diabetes and Obesity at Helmholtz Munich. For over 16 years, Prof. Dr. Garcia Caceres has focused on understanding how the hypothalamus controls energy balance, particularly through astrocytes. Her research aims to uncover the cellular mechanisms underlying obesity and metabolic disorders. Her pioneering work, awarded with ERC Starting Grant, has shown that the brain's control of energy and glucose metabolism involves astrocytes. By exploring the interactions between neurons, astroglia, and blood vessels, she seeks insights to inform strategies for obesity prevention and treatment, including associated conditions like hypertension. Additionally, her recent research extends to understanding how the brain integrates peripheral endocrine cues into hypothalamic circuits, critical for metabolic adaptation in diet-induced obesity. Overall, her discoveries challenge traditional obesity treatment models and underscore the importance of considering sex as a biological variable in addressing this health issue. [more]

Parkinson’s is a debilitating neurodegenerative disease affecting nearly 10 million people worldwide. The pathology appears to depend on the diffusion of abnormal aggregates of the endogenous α-synuclein protein across the nervous system. How the diffusion occurs remains controversial. Clinical evidence suggests that the gastrointestinal tract is a site of origin for α-synuclein, which then may spread to the brain. I will present studies in mice in which we tried to map the body-brain pathways via which the pathology may spread from the gut. I will also mention the potential role of gut immune cells in this process. [more]

A variety of environmental stressors, such as temperature (hot and cold), infection, natural enemies, and starvation, can threaten life. To survive environmental stresses, mammals exert autonomic and behavioral responses as fundamental functions mediated by the CNS. Remarkable progress has recently been made in understanding the central circuit mechanisms of physiological responses to such stressors. A “trunk” neural pathway from the dorsomedial hypothalamus (DMH) to the rostral medullary raphe region (rMR) regulates sympathetic outflows to effector organs for homeostasis. Thermal and infection stress inputs to the preoptic area of the hypothalamus dynamically alter the DMH→rMR transmission to elicit thermoregulatory, febrile, and cardiovascular responses. Psychological stress signaling from the prefrontal cortex to the DMH drives sympathetic and behavioral responses for stress coping, representing a psychosomatic connection from the corticolimbic emotion circuit to the autonomic and somatic motor systems. Under starvation stress, medullary reticular neurons activated by hunger signaling from the hypothalamus suppress thermogenic drive from the rMR for energy saving and prime mastication to promote food intake. I will present a unified neural network for environmental stress responses, which provides novel insights into the integrative central regulation of organ functions that enables mammals to inhabit diverse environments on earth. [more]