The Brain Economy: Advancing Brain Science to Better Understand the Modern Economy.

The coming years are likely to be turbulent due to a myriad of factors or polycrisis, including an escalation in climate extremes, emerging public health threats, weak productivity, increases in global economic instability and further weakening in the integrity of global democracy. These formidable challenges are not exogenous to the economy but are in some cases generated by the system itself. They can be overcome, but only with far-reaching changes to global economics. Our current socio-economic paradigm is insufficient for addressing these complex challenges, let alone sustaining human development, well-being and happiness. To support the flourishing of the global population in the age of polycrisis, we need a novel, person-centred and collective paradigm. The brain economy leverages insights from neuroscience to provide a novel way of centralising the human contribution to the economy, how the economy in turn shapes our lives and positive feedbacks between the two. The brain economy is primarily based on Brain Capital, an economic asset integrating brain health and brain skills, the social, emotional, and the diversity of cognitive brain resources of individuals and communities. People with healthy brains are essential to navigate increasingly complex systems. Policies and investments that improve brain health and hence citizens' cognitive functions and boost brain performance can increase productivity, stimulate greater creativity and economic dynamism, utilise often underdeveloped intellectual resources, afford social cohesion, and create a more resilient, adaptable and sustainability-engaged population.

Distinct neuron phenotypes may serve object feature sensing in the electrosensory lobe of Gymnotus omarorum.

Early sensory relay circuits in the vertebrate medulla often adopt a cerebellum-like organization specialized for comparing primary afferent inputs with central expectations. These circuits usually have a dual output, carried by center ON and center OFF neurons responding in opposite ways to the same stimulus at the center of their receptive fields. Here, we show in the electrosensory lateral line lobe of Gymnotiform weakly electric fish that basilar pyramidal neurons, representing 'ON' cells, and non-basilar pyramidal neurons, representing 'OFF' cells, have different intrinsic electrophysiological properties. We used classical anatomical techniques and electrophysiological in vitro recordings to compare these neurons. Basilar neurons are silent at rest, have a high threshold to intracellular stimulation, delayed responses to steady-state depolarization and low pass responsiveness to membrane voltage variations. They respond to low-intensity depolarizing stimuli with large, isolated spikes. As stimulus intensity increases, the spikes are followed by a depolarizing after-potential from which phase-locked spikes often arise. Non-basilar neurons show a pacemaker-like spiking activity, smoothly modulated in frequency by slow variations of stimulus intensity. Spike-frequency adaptation provides a memory of their recent firing, facilitating non-basilar response to stimulus transients. Considering anatomical and functional dimensions, we conclude that basilar and non-basilar pyramidal neurons are clear-cut, different anatomo-functional phenotypes. We propose that, in addition to their role in contrast processing, basilar pyramidal neurons encode sustained global stimuli such as those elicited by large or distant objects while non-basilar pyramidal neurons respond to transient stimuli due to movement of objects with a textured surface.

Cell Proliferation, Migration, and Neurogenesis in the Adult Brain of the Pulse Type Weakly Electric Fish, Gymnotus omarorum.

Adult neurogenesis, an essential mechanism of brain plasticity, enables brain development along postnatal life, constant addition of new neurons, neuronal turnover, and/or regeneration. It is amply distributed but negatively modulated during development and along evolution. Widespread cell proliferation, high neurogenic, and regenerative capacities are considered characteristics of teleost brains during adulthood. These anamniotes are promising models to depict factors that modulate cell proliferation, migration, and neurogenesis, and might be intervened to promote brain plasticity in mammals. Nevertheless, the migration path of derived cells to their final destination was not studied in various teleosts, including most weakly electric fish. In this group adult brain morphology is attributed to sensory specialization, involving the concerted evolution of peripheral electroreceptors and electric organs, encompassed by the evolution of neural networks involved in electrosensory information processing. In wave type gymnotids adult brain morphology is proposed to result from lifelong region specific cell proliferation and neurogenesis. Consistently, pulse type weakly electric gymnotids and mormyrids show widespread distribution of proliferation zones that persists in adulthood, but their neurogenic potential is still unknown. Here we studied the migration process and differentiation of newborn cells into the neuronal phenotype in the pulse type gymnotid Gymnotus omarorum. Pulse labeling of S-phase cells with 5-Chloro-2'-deoxyuridine thymidine followed by 1 to 180 day survivals evidenced long distance migration of newborn cells from the rostralmost telencephalic ventricle to the olfactory bulb, and between layers of all cerebellar divisions. Shorter migration appeared in the tectum opticum and torus semicircularis. In many brain regions, derived cells expressed early neuronal markers doublecortin (chase: 1-30 days) and HuC/HuD (chase: 7-180 days). Some newborn cells expressed the mature neuronal marker tyrosine hydroxylase in the subpallium (chase: 90 days) and olfactory bulb (chase: 180 days), indicating the acquisition of a mature neuronal phenotype. Long term CldU labeled newborn cells of the granular layer of the corpus cerebelli were also retrogradely labeled "in vivo," suggesting their insertion into the neural networks. These findings evidence the neurogenic capacity of telencephalic, mesencephalic, and rhombencephalic brain proliferation zones in G. omarorum, supporting the phylogenetic conserved feature of adult neurogenesis and its functional significance.

Post-hatching brain morphogenesis and cell proliferation in the pulse-type mormyrid Mormyrus rume proboscirostris.

The anatomical organization of African Mormyrids' brain is a clear example of departure from the average brain morphotype in teleosts, probably related to functional specialization associated to electrosensory processing and sensory-motor coordination. The brain of Mormyrids is characterized by a well-developed rhombencephalic electrosensory lobe interconnected with relatively large mesencephalic torus semicircularis and optic tectum, and a huge and complex cerebellum. This unique morphology might imply cell addition from extraventricular proliferation zones up to late developmental stages. Here we studied the ontogeny of these brain regions in Mormyrus rume proboscirostris from embryonic to adult stages by classical histological techniques and 3D reconstruction, and analyzed the spatial-temporal distribution of proliferating cells, using pulse type BrdU labeling. Brain morphogenesis and maturation progressed in rostral-caudal direction, from 4day old free embryos, through larvae, to juveniles whose brain almost attained adult morphological complexity. The change in the relative size of the telencephalon, and mesencephalic and rhombencephalic brain regions suggest a developmental shift in the relative importance of visual and electrosensory modalities. In free embryos, proliferating cells densely populated the lining of the ventricular system. During development, ventricular proliferating cells decreased in density and extension of distribution, constituting ventricular proliferation zones. The first recognizable one was found at the optic tectum of free embryos. Several extraventricular proliferation zones were found in the cerebellar divisions of larvae, persisting along life. Adult M. rume proboscirostris showed scarce ventricular but profuse cerebellar proliferation zones, particularly at the subpial layer of the valvula cerebelli, similar to lagomorphs. This might indicate that adult cerebellar proliferation is a conserved vertebrate feature.

Spatial distribution and cellular composition of adult brain proliferative zones in the teleost, Gymnotus omarorum.

Proliferation of stem/progenitor cells during development provides for the generation of mature cell types in the CNS. While adult brain proliferation is highly restricted in the mammals, it is widespread in teleosts. The extent of adult neural proliferation in the weakly electric fish, Gymnotus omarorum has not yet been described. To address this, we used double thymidine analog pulse-chase labeling of proliferating cells to identify brain proliferation zones, characterize their cellular composition, and analyze the fate of newborn cells in adult G. omarorum. Short thymidine analog chase periods revealed the ubiquitous distribution of adult brain proliferation, similar to other teleosts, particularly Apteronotus leptorhynchus. Proliferating cells were abundant at the ventricular-subventricular lining of the ventricular-cisternal system, adjacent to the telencephalic subpallium, the diencephalic preoptic region and hypothalamus, and the mesencephalic tectum opticum and torus semicircularis. Extraventricular proliferation zones, located distant from the ventricular-cisternal system surface, were found in all divisions of the rombencephalic cerebellum. We also report a new adult proliferation zone at the caudal-lateral border of the electrosensory lateral line lobe. All proliferation zones showed a heterogeneous cellular composition. The use of short (24 h) and long (30 day) chase periods revealed abundant fast cycling cells (potentially intermediate amplifiers), sparse slow cycling (potentially stem) cells, cells that appear to have entered a quiescent state, and cells that might correspond to migrating newborn neural cells. Their abundance and migration distance differed among proliferation zones: greater numbers and longer range and/or pace of migrating cells were associated with subpallial and cerebellar proliferation zones.

Postnatal brain development of the pulse type, weakly electric gymnotid fish Gymnotus omarorum.

Teleosts are a numerous and diverse group of fish showing great variation in body shape, ecological niches and behaviors, and a correspondent diversity in brain morphology, usually associated with their functional specialization. Weakly electric fish are a paradigmatic example of functional specialization, as these teleosts use self-generated electric fields to sense the nearby environment and communicate with conspecifics, enabling fish to better exploit particular ecological niches. We analyzed the development of the brain of the pulse type gymnotid Gymnotus omarorum, focusing on the brain regions involved directly or indirectly in electrosensory information processing. A morphometric analysis has been made of the whole brain and of brain regions of interest, based on volumetric data obtained from 3-D reconstructions to study the growth of the whole brain and the relative growth of brain regions, from late larvae to adulthood. In the smallest studied larvae some components of the electrosensory pathway appeared to be already organized and functional, as evidenced by tract-tracing and in vivo field potential recordings of electrosensory-evoked activity. From late larval to adult stages, rombencephalic brain regions (cerebellum and electrosensory lateral line lobe) showed a positive allometric growth, mesencephalic brain regions showed a negative allometric growth, and the telencephalon showed an isometric growth. In a first step towards elucidating the role of cell proliferation in the relative growth of the analyzed brain regions, we also studied the spatial distribution of proliferation zones by means of pulse type BrdU labeling revealed by immunohistochemistry. The brain of G. omarorum late larvae showed a widespread distribution of proliferating zones, most of which were located at the ventricular-cisternal lining. Interestingly, we also found extra ventricular-cisternal proliferation zones at in the rombencephalic cerebellum and electrosensory lateral line lobe. We discuss the role of extraventricular-cisternal proliferation in the relative growth of the latter brain regions.

Waveform generation in the weakly electric fish Gymnotus coropinae (Hoedeman): the electric organ and the electric organ discharge.

This article deals with the electric organ and its discharge in Gymnotus coropinae, a representative species of one of the three main clades of the genus. Three regions with bilateral symmetry are described: (1) subopercular (medial and lateral columns of complex shaped electrocytes); (2) abdominal (medial and lateral columns of cuboidal and fusiform electrocytes); and (3) main [four columns, one dorso-lateral (containing fusiform electrocytes) and three medial (containing cuboidal electrocytes)]. Subopercular electrocytes are all caudally innervated whereas two of the medial subopercular ones are also rostrally innervated. Fusiform electrocytes are medially innervated at the abdominal portion, and at their rostral and caudal poles at the main portion. Cuboidal electrocytes are always caudally innervated. The subopercular portion generates a slow head-negative wave (V(1r)) followed by a head-positive spike (V(3r)). The abdominal and main portions generate a fast tetra-phasic complex (V(2345ct)). Since subopercular components prevail in the near field and the rest in the far field, time coincidence of V(3r) with V(2) leads to different waveforms depending on the position of the receiver. This confirms the splitting hypothesis of communication and exploration channels based on the different timing, frequency band and reach of the regional waveforms. The following hypothesis is compatible with the observed anatomo-functional organization: V(1r) corresponds to the rostral activation of medial subopercular electrocytes and V(3r) to the caudal activation of all subopercular electrocytes; V(2), and part of V(3ct), corresponds to the successive activation of the rostral and caudal poles of dorso-lateral fusiform electrocytes; and V(345ct) is initiated in the caudal face of cuboidal electrocytes by synaptic activation (V(3ct)) and it is completed (V(45ct)) by the successive activation of rostral and caudal faces by the action currents evoked in the opposite face.

Active electroreception in Gymnotus omari: imaging, object discrimination, and early processing of actively generated signals.

Weakly electric fishes "electrically illuminate" the environment in two forms: pulse fishes emit a succession of discrete electric discharges while wave fishes emit a continuous wave. These strategies are present in both taxonomic groups of weakly electric fishes, mormyrids and gymnotids. As a consequence one can distinguish four major types of active electrosensory strategies evolving in parallel. Pulse gymnotids have an electrolocating strategy common with pulse mormyrids, but brains of pulse and wave gymnotids are alike. The beating strategy associated to other differences in the electrogenic system and electrosensory responses suggests that similar hardware might work in a different mode for processing actively generated electrosensory images. In this review we summarize our findings in pulse gymnotids' active electroreception and outline a primary agenda for the next research.

Sensory processing in the fast electrosensory pathway of pulse gymnotids studied at multiple integrative levels.

Pulse gymnotids extract information about the environment using the pulsed discharge of an electric organ. Cutaneous electroreceptor organs transduce and encode the changes that objects imprint on the self-generated transcutaneous electric field. This review deals with the role of a neural circuit, the fast electrosensory path of pulse gymnotids, in the streaming of self generated electrosensory signals. The activation of this path triggers a low-responsiveness window slightly shorter than the interval between electric organ discharges. This phenomenon occurs at the electrosensory lateral line lobe where primary afferent terminals project on the somata of spherical neurons. The main subservient mechanism of the low-responsiveness window rely on the intrinsic properties of spherical neurons (dominated by a voltage dependent, low-threshold, non-inactivating and slowly-deactivating K(+) conductance) determining the cell to respond with a single spike followed by a long refractory period. Externally generated signals that randomly occur within the interval between self-generated discharges are likely blocked by the low responsiveness window. Repetitive signals, as those emitted by conspecifics with a slightly lower rate, occur progressively at longer delays beyond the duration of the low responsiveness window. Transient increases of the discharge rate relocate the interference within the low-responsiveness window. We propose that this combination of sensory filtering and electromotor control favors the self-generated signals in detriment of other, securing the continuity of the electrolocation stream.

Post-natal development of the electromotor system in a pulse gymnotid electric fish.

Some fish emit electric fields generated by the coordinated activation of electric organs. Such discharges are used for exploring the environment and for communication. This article deals with the development of the electric organ and its discharge in Gymnotus, a pulse genus in which brief discharges are separated by regular silent intervals. It is focused on the anatomo-functional study of fish sized between 10 and 300 mm from the species of Gymnotus, in which electrogenic mechanisms are best known. It was shown that: (1) electroreception and electromotor control is present from early larval stages; (2) there is a single electric organ from larval to adult stages; (3) pacemaker rhythmicity becomes similar to that of the adult when the body length becomes greater than 45 mm and (4) there is a consistent developmental profile of the electric organ discharge in which waveform components are added according to a programmed sequence. The analysis of these data allowed us to identify three main periods in post-natal development of electrogenesis: (1) before fish reach 55 mm in length, when maturation of neural structures is the main factor determining a characteristic sequence of changes observed in the discharge timing and waveform; (2) between 55 and 100 mm in length, when peripheral maturation of the effector cells and changes in post-effector mechanisms due to the fish's growth determine minor changes in waveform and the increase in amplitude of the discharge and (3) beyond 100 mm in length, when homothetic growth of the fish body explains the continuous increase in electric power of the discharge.

The role of single spiking spherical neurons in a fast sensory pathway.

One difficulty in understanding the brain is that of linking the structure of the neurons with their computational roles in neural circuits. In this paper we address this subject in a relative simple system, the fast electrosensory pathway of an electric fish, where sensory images are coded by the relative latency of a volley of single spikes. The main input to this path is a stream of discrete electric images resulting from the modulation of a self-generated carrier by the environment. At the second order cell level, a window of low responsiveness, reducing potential interference from other stimuli, follows activation of the path. In the present study, we further characterize the input-output relationship at the second order neurons by recording field potentials, and ascertain its cellular basis using in vitro whole cell patch recordings. The field potentials from freely behaving, socially interacting fish were obtained from chronically implanted fish restrained in a mesh pen. In addition, at the end of some experiments the fish was curarized and the fast electrosensory path responses to artificial stimuli were further explored. These in vivo approaches showed that larger stimuli cause larger and longer windows of low responsiveness. The simple spherical geometry of the second order cells allowed us to unveil the membrane mechanisms underlying this phenomenon in vitro. These spherical cells respond with a single spike at the onset of current steps of any amplitude and duration, showing inward and outward rectification, and a long refractory period. We postulate that a low-threshold K+ conductance generates the outward rectification. The most parsimonious interpretation of our data indicates that slow deactivation of this conductance causes the long refractory period. These non-linear properties of the membrane explain the single spiking profile of spherical cells and the low-responsiveness window observed in vivo. Since the electric organ discharges are emitted at intervals slightly longer than the duration of the low-responsiveness window, we propose that the described cellular mechanisms allow fish streaming self-generated images.

Electrolocation and electrocommunication in pulse gymnotids: signal carriers, pre-receptor mechanisms and the electrosensory mosaic.

Constraints introduced by signal carriers, pre-receptor mechanisms and receptor transduction are fundamental for shaping the signals used by the brain to build up perceptual images. This review analyses some of these constraints in the electrosensory system of pulse Gymnotids. First, it describes the characteristics and differences of electrolocation and electrocommunication carriers. Second, it analyses the role of electrogenic and non-electrogenic tissues of the fish body in the generation and conditioning of these carriers. Two pre-receptor mechanisms are discussed: (a) the funneling of currents to the perioral region and (b) a Mexican-hat profile involved in edge detection. Finally, some characteristics of the electroreceptor structure and the sensory mosaic are examined. We conclude that there is an electrosensory fovea at the perioral region where a large density and variety of receptors is stimulated by self- and conspecific-generated currents funneled there by non electrogenic tissues. Differences in carrier waveform may be used to distinguish between reafferent and communication signals.