Physiology seminars

Since Darwin, comparative research has shown that most animals share basic timing capacities, such as the ability to process temporal regularities and produce rhythmic behaviors. What seems to be more exclusive, however, are the capacities to generate temporal predictions and to display anticipatory behavior at salient time points. These abilities are associated with subcortical structures like basal ganglia (BG) and cerebellum (CE), which are more developed in humans as compared to nonhuman animals. In the first research line, we investigated the basic capacities to extract temporal regularities from the acoustic environment and produce temporal predictions. We did so by adopting a comparative and translational approach, thus making use of a unique EEG dataset including 2 macaque monkeys, 20 healthy young, 11 healthy old participants and 22 stroke patients, 11 with focal lesions in the BG and 11 in the CE. In the second research line, we holistically explore the functional relevance of body-brain physiological interactions in human behavior. Thus, a series of planned studies investigate the functional mechanisms by which body signals (e.g., respiratory and cardiac rhythms) interact with and modulate neurocognitive functions from rest and sleep states to action and perception. This project supports the effort towards individual profiling: are individuals’ timing capacities (e.g., rhythm perception and production), and general behavior (e.g., individual walking and speaking rates) influenced / shaped by body-brain interactions?

Understanding the brain is not only intrinsically fascinating, but also highly relevant to increase our well-being since our brain exhibits a power over the body that makes it capable both of provoking illness or facilitating the healing process. Bearing in mind this dark force, brain sciences have undergone and will undergo an important revolution, redefining its boundaries beyond the cranial cavity. During this presentation, we will discuss about the communication between the brain and other systems that shapes how we feel the external word and how we think. We are starting to unravel how our organs talk to the brain and how the brain talks back. That two-way communication encompasses a complex, body-wide system of nerves, hormones and other signals that will be discussed. This presentation aims at challenging a long history of thinking of bodily regulation as separate from "higher" mental processes. Four centuries ago, René Descartes famously conceptualized the mind as being separate from the body, it is time now to embody our mind.

Gut-derived signals regulate metabolism, appetite, and behaviors important for mental health. We have performed a large-scale multidimensional screen to identify gut hormones and nutrient-sensing mechanisms in the intestine that regulate metabolism and behavior in the fruit fly Drosophila. We identified several gut hormones that affect fecundity, stress responses, metabolism, feeding, and sleep behaviors, many of which seem to act sex-specifically. We show that in response to nutrient intake, the enteroendocrine cells (EECs) of the adult Drosophila midgut release hormones that act via inter-organ relays to coordinate metabolism and feeding decisions. These findings suggest that crosstalk between the gut and other tissues regulates food choice according to metabolic needs, providing insight into how that intestine processes nutritional inputs and into the gut-derived signals that relay information regulating nutrient-specific hungers to maintain metabolic homeostasis.

The hypothalamus controls diverse homeostatic functions including fertility. Neural episode generators are required to drive the intermittent pulsatile and surge profiles of reproductive hormone secretion that control gonadal function. Studies in genetic mouse models have been fundamental in defining the neural circuits forming these central pattern generators and the full range of in vitro and in vivo optogenetic and chemogenetic methodologies have enabled investigation into their mechanism of action. The seminar will outline studies defining the hypothalamic “GnRH pulse generator network” and current understanding of its operation to drive pulsatile hormone secretion.

Understanding the brain is not only intrinsically fascinating, but also highly relevant to increase our well-being since our brain exhibits a power over the body that makes it capable both of provoking illness or facilitating the healing process. Bearing in mind this dark force, brain sciences have undergone and will undergo an important revolution, redefining its boundaries beyond the cranial cavity. During this presentation, we will discuss about the communication between the brain and other systems that shapes how we feel the external word and how we think. We are starting to unravel how our organs talk to the brain and how the brain talks back. That two-way communication encompasses a complex, bodywide system of nerves, hormones and other signals that we will discussed. This presentation aims at challenging a long history of thinking of bodily regulation as separate from "higher" mental processes. Four centuries ago, René Descartes famously conceptualized the mind as being separate from the body, it is time now to embody our mind.

The brain combines signals across the eyes. This process is well-characterized for the perceptual anatomical pathway through V1 that primarily codes contrast, where interocular normalization ensures that responses are approximately equal for monocular and binocular stimulation. But we have much less understanding of how luminance is combined binocularly, both in the cortex and in subcortical structures that govern pupil diameter. Here I will describe the results of experiments using a novel combined EEG and pupillometry paradigm to simultaneously index binocular combination of luminance flicker in parallel pathways. The results show evidence of a more linear process than for spatial contrast, that may reflect different operational constraints in distinct anatomical pathways.

Beyond vision, light triggers a variety of non-image forming responses. Amongst these is the pupillary light reflex, commonly used by ophthalmologists to gauge the function of the optic nerve head. In my talk, I will share some of our latest work on optimizing the use of the pupillary light reflex to detect functional loss in ocular diseases in clinics.

Do all components of the living human eye have a measurable diurnal rhythm? In this talk I will discuss methodologies and results of studies on adolescents and young adults. I will also touch upon the associations between diurnal rhythms of the eye and behavioral activities.

Night shift work is associated with adverse health effects and leads to misalignment between timing cues from the environment and the endogenous circadian clock. In this presentation, I will discuss the effect of circadian misalignment induced by night shift work on peripheral 24-h rhythms on the transcriptome and metabolome in humans, presenting findings from both controlled laboratory studies and field studies. Furthermore, I will highlight the importance of taking into account interindividual differences in the response to circadian misalignment.

A critical function of sensory systems is to reliably extract ethologically relevant features from the complex natural environment. A classic model to study feature detection is the direction-selective circuit of the mammalian retina. In this talk, I will discuss our recent work on how visual contexts dynamically influence the neural processing of motion signals in the direction-selective circuit in the mouse retina.

Brain aging leads to cognitive decline and is the main risk factor for sporadic forms of neurodegenerative diseases including Alzheimer’s disease. While brain cell- and tissue-intrinsic factors are likely key determinants of the aging process recent studies document a remarkable susceptibility of the brain to circulatory factors. Thus, blood borne factors from young mice or humans are sufficient to slow aspects of brain aging and improve cognitive function in old mice and, vice versa, factors from old mice are detrimental for young mice and impair cognition. We found evidence that the cerebrovasculature is an important target of circulatory factors and that brain endothelial cells show prominent age-related transcriptional changes in response to plasma. Furthermore, plasma proteins are taken up broadly into the young brain through receptor mediated transport which declines with aging. At the same time, brain derived proteins are detectable in plasma allowing us to measure physiological changes linked to brain aging in plasma. We are exploring the relevance of these findings for neurodegeneration and potential applications towards therapies.

Since the discovery of the intrinsically photosensitive retinal ganglion cells (ipRGCs) – just two decades ago – substantial work has been carried out trying to understand their functioning. In this seminar, I’ll focus on pupillometry studies that have provided key clues about ipRGC behavior. Specifically, the interaction between the intrinsic response, rods, and cones will be discussed.

Laboratory studies have shown that meaningful changes in light exposure lead to phase shifts in melatonin rhythm. In natural settings, however, light is a very complex signal. How melatonin responds to weekly- and seasonal-dependent variations in light exposure is still poorly understood. In this talk I will present results from a series of observational and intervention studies on the relationship between melatonin and light exposure in the field.

Liset M de la Prida is a Physicist (1994) and PhD in Neuroscience (1998), who leads the Laboratorio de Circuitos Neuronales at the Instituto Cajal, Madrid, Spain (http://www.hippo-circuitlab.es). The main focus of her lab is to understand the function of the hippocampal circuits in the normal and the diseased brain, in particular oscillations and neuronal representations. She is a leading international expert in the study of the basic mechanisms of physiological ripples and epileptic fast ripples, with strong visibility as developer of novel groundbreaking electrophysiological tools. Dr. de la Prida serves as an Editor for prestigious journals including eLife, Journal of Neuroscience Methods and eNeuro, and has commissioning duties in the American Epilepsy Society, FENS and the Spanish Society for Neurosciences.

The research in my lab focuses on sensory signal processing, particularly in cases where sensory systems perform at or near the limits imposed by physics. Photon counting in the visual system is a beautiful example. At its peak sensitivity, the performance of the visual system is limited largely by the division of light into discrete photons. This observation has several implications for phototransduction and signal processing in the retina: rod photoreceptors must transduce single photon absorptions with high fidelity, single photon signals in photoreceptors, which are only 0.03 – 0.1 mV, must be reliably transmitted to second-order cells in the retina, and absorption of a single photon by a single rod must produce a noticeable change in the pattern of action potentials sent from the eye to the brain. My approach is to combine quantitative physiological experiments and theory to understand photon counting in terms of basic biophysical mechanisms. Fortunately there is more to visual perception than counting photons. The visual system is very adept at operating over a wide range of light intensities (about 12 orders of magnitude). Over most of this range, vision is mediated by cone photoreceptors. Thus adaptation is paramount to cone vision. Again one would like to understand quantitatively how the biophysical mechanisms involved in phototransduction, synaptic transmission, and neural coding contribute to adaptation.

The arousal construct underlies a spectrum of behaviors that include sleep, exploration, feeding, sexual activity and adaptive stress. Pathological arousal conditions include stress, anxiety disorders, and addiction. The dynamics between arousal state transitions are modulated by norepinephrine neurons in the locus coeruleus, histaminergic neurons in the hypothalamus, dopaminergic neurons in the mesencephalon and cholinergic neurons in the basal forebrain. The hypocretin/orexin system in the lateral hypothalamus I will also present a new mechanism underlying sleep fragmentation during aging. Hcrt neurons are hyperexcitable in aged mice. We identify a potassium conductance known as the M-current, as a critical player in maintaining excitability of Hcrt neurons. Genetic disruption of KCNQ channels in Hcrt neurons of young animals results in sleep fragmentation. In contrast, treatment of aged animals with a KCNQ channel opener restores sleep/wake architecture. These data point to multiple circuits modulating sleep integrity across lifespan.

Information processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy usage are regulated during food scarcity. I addressed this in the visual cortex of awake mice using whole-cell recordings and two-photon imaging to monitor layer 2/3 neuronal activity and ATP usage. I found that food restriction reduced synaptic ATP usage by 29% through a decrease in AMPA receptor conductance. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting membrane potential. Consequently, neurons spiked at similar rates as controls, but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost since it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening in orientation tuning and impaired fine visual discrimination. This reduction in coding precision was associated with reduced levels of the fat mass-regulated hormone leptin and was restored by exogenous leptin supplementation. These findings reveal novel mechanisms that dynamically regulate energy usage and coding precision in neocortex.

Leonard Maler will focus on a specialized caudal portion of the cerebellum of teleost fish whose structure and physiology has been especially well studies to the point that we now have detailed computational analyses of its function. Idoia Quintana-Urzainqui will talk about what sharks can tell us about the evolution of the telencephalon, mainly focusing on the evolutionary expansion of the pallium and how shark embryos can hold key information to interpret the origin of the developmental processes that triggered this phenomenon.