Seminars and events

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]

Serotonin has wide-ranging effects on many physiological activities, from feeding and gut motility to mood and motor learning. However, the identity of central serotonergic neurons and the neuronal circuits within which they are embedded are largely unknown at single cell and synaptic level. We have used a scanning transmission electron microscopy dataset of a whole Drosophila larva to elucidate the central sensory-motor circuit that controls swallowing and its coordination with the enteric nervous system. The circuit is composed of Piezo-expressing mechanosensory neurons arrayed along the esophagus which are able to sense the passage of food. Their afferent signal is conveyed onto a set of central serotonergic neurons that project back out via the larval vagus nerve and facilitates swallowing motor pattern. Serotonin release by these neurons modulates serotonin receptor-expressing motor neurons that innervate the muscles underlying esophageal peristalsis. These motor neurons also share an efferent copy of their motor activity with the Piezo neurons sensing food passage. Our analysis reveals an elemental circuit architecture through which successful completion of a rewarding motor task provides a reinforcing and stabilizing signal to the CNS for facilitation of motor learning. [more]

The brain and body are in a continuous dialog that is essential for our physical and mental health. Little is known about how this dialog is achieved at the neurobiological level. A large corpus of work implicates the insular cortex as a central node for bi-directional brain-body communication. However, direct evidence for its functional role is scarce. We developed a microprism-based cellular imaging approach to monitor insular cortex activity in behaving mice across different physiological need states. We combine this imaging approach with manipulations of peripheral physiology and related hypothalamic circuits to investigate the underlying mechanisms. I will first present our recent data suggesting that insular cortex population activity represents both current bodily states, as well as future predicted ones. I will then describe our current efforts to understand these predictions under conditions of conflicting physiological needs, and the potential role of these predictions in regulating bodily physiology. [more]

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Psychedelics, including psilocybin and LSD, are undergoing a “renaissance” as possible treatments for a range of psychiatric and neurological disorders, especially because of their fast onset of therapeutic activity. There has been a rapid push to clinical trials since the 2018 designation of psilocybin as a “breakthrough therapy” by the US FDA, based on its efficacy in treatment-resistant depression, including 4 clinical trials currently underway in patients with anorexia nervosa (AN). While the outcomes of these trials will show efficacy one way or the other, it is imperative to understand the biological mechanisms through which psilocybin may act to produce therapeutic outcomes, in order to best direct treatment to individuals likely to respond. This is especially important given the climate of intense media hype that may bias the outcomes of clinical trials based on an expectation of efficacy. We have tested the effects of a single dose of psilocybin on the development of pathological weight loss in the most well-established animal model of AN, known as activity-based anorexia, and suggest a role for reinforcement learning and behavioural flexibility in the positive effects of psilocybin on energy balance. We are now focused on uncovering the neurobiological substrates that underpin these effects, by examining changes in serotonin receptor expression and the brain-derived neurotropic factor (BDNF) signalling pathway. [more]

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The Melanin-concentrating hormone (MCH) is a neuropeptide implicated in a wide range of functions. Its role is best described as an orexigenic peptide since acute MCH applications induce an increase in food intake. MCH-immunoreactive fibers (MCH-ir) are found diffused throughout virtually the entire CNS. In contrast, the production of MCH and messenger RNA (mRNA) from its precursor (ppMCH) is concentrated, in mammals, in neurons of two hypothalamic regions: the lateral hypothalamic area [LHA] and the incerto-hypothalamic area (IHy). Only during lactation, MCH-ir neurons and ppMCH mRNA expression appear in new hypothalamic territories, such as the ventromedial part of the medial preoptic area (vmMPOA). The amount of MCH synthesis in this region increases with the progress of lactation, being maximum in the final phase [around 19th- 21st days] when it disappears. The origin of these cells is still unknown. A possible explanation for this phenomenon is the de novo appearance or neuroplasticity of those cells in the vmMPOA region, which would characterize the necessity of MCH signaling to decline the maternal behavior/lactation period of lactating females. [more]

In aging populations, questions around the processes of aging become more and more pressing as aging-associated and neurodegenerative diseases such as Alzheimer’s, Parkinson’s and diabetes mellitus increasingly strain our health systems. Understanding the molecular mechanisms involved in degenerative aging processes can help develop new therapeutic approaches that lead to a healthier way of living for older and ill individuals, and eventually for us all. [more]