Perinatal Docosahexaenoic Acid Supplementation Improves Cognition and Alters Brain Functional Organization in Piglets.

Epidemiologic studies associate maternal docosahexaenoic acid (DHA)/DHA-containing seafood intake with enhanced cognitive development; although, it should be noted that interventional trials show inconsistent findings. We examined perinatal DHA supplementation on cognitive performance, brain anatomical and functional organization, and the brain monoamine neurotransmitter status of offspring using a piglet model. Sows were fed a control (CON) or a diet containing DHA (DHA) from late gestation throughout lactation. Piglets underwent an open field test (OFT), an object recognition test (ORT), and magnetic resonance imaging (MRI) to acquire anatomical, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI) at weaning. Piglets from DHA-fed sows spent 95% more time sniffing the walls than CON in OFT and exhibited an elevated interest in the novel object in ORT, while CON piglets demonstrated no preference. Maternal DHA supplementation increased fiber length and tended to increase fractional anisotropy in the hippocampus of offspring than CON. DHA piglets exhibited increased functional connectivity in the cerebellar, visual, and default mode network and decreased activity in executive control and sensorimotor network compared to CON. The brain monoamine neurotransmitter levels did not differ in healthy offspring. Perinatal DHA supplementation may increase exploratory behaviors, improve recognition memory, enhance fiber tract integrity, and alter brain functional organization in offspring at weaning

Insects have the capacity for subjective experience

To what degree are non-human animals conscious? We propose that the most meaningful way to approach this question is from the perspective of functional neurobiology. Here we focus on subjective experience, which is a basic awareness of the world without further reflection on that awareness. This is considered the most basic form of consciousness. Tellingly, this capacity is supported by the integrated midbrain and basal ganglia structures, which are among the oldest and most highly conserved brain systems in vertebrates. A reasonable inference is that the capacity for subjective experience is both widespread and evolutionarily old within the vertebrate lineage. We argue that the insect brain supports functions analogous to those of the vertebrate midbrain and hence that insects may also have a capacity for subjective experience. We discuss the features of neural systems which can and cannot be expected to support this capacity as well as the relationship between our arguments based on neurobiological mechanism and our approach to the “hard problem” of conscious experience

Evolution of Xenopus Vocal Patterns: Retuning a Hindbrain Circuit During Species Divergence

Circuits underlying motor patterns of closely related species provide an ideal framework in which to study how evolution shapes behavioral variation. Male African clawed frogs (Xenopus and Silurana) advertisement call to attract female mates and silence male rivals. Males of each species produce a unique vocal pattern that serves as a species-identifier. Xenopus laevis is the most well-studied species in terms of its vocal behavior and underlying anatomy and physiology. The clade that includes X. laevis, or X. laevis senso lato, also includes 3 other species that diverged ~8.5 million years ago. All 4 of these species produce advertisement calls that include fast trills – trains of fast rate (~60 Hz) sound pulses. However, their calls differ substantially between species in measures of trill duration and period. I examined the premotor circuit underlying vocal patterning in three of these species: X. laevis, X. petersii, and X. victorianus. I used extracellular recordings to find that a premotor nucleus, DTAM, which is part of the vocal central pattern generator, is the likely source of species-variation of vocal patterns. Species-specific trill duration and period are intrinsic to the region of the hindbrain that includes DTAM. Next, I used blind whole-cell patch recordings in DTAM of X. laevis and X. petersii to examine the cells that encode trill duration and period. I identified homologous populations of premotor vocal cells in both species that code for trill duration and period in a species-specific manner. Together, these results support an autonomous role of the DTAM circuit for generation of species variation in call duration and period

Human metabolic adaptations and prolonged expensive neurodevelopment: A review

1.	After weaning, human hunter-gatherer juveniles receive substantial (≈3.5-7 MJ day^-1^), extended (≈15 years) and reliable (kin and nonkin food pooling) energy provision.
2.	The childhood (pediatric) and the adult human brain takes a very high share of both basal metabolic rate (BMR) (child: 50-70%; adult: ≈20%) and total energy expenditure (TEE) (child: 30-50%; adult: ≈10%).
3.	The pediatric brain for an extended period (≈4-9 years-of-age) consumes roughly 50% more energy than the adult one, and after this, continues during adolescence, at a high but declining rate. Within the brain, childhood cerebral gray matter has an even higher 1.9 to 2.2-fold increased energy consumption. 
4.	This metabolic expensiveness is due to (i) the high cost of synapse activation (74% of brain energy expenditure in humans), combined with (ii), a prolonged period of exuberance in synapse numbers (up to double the number present in adults). Cognitive development during this period associates with volumetric changes in gray matter (expansion and contraction due to metabolic related size alterations in glial cells and capillary vascularization), and in white matter (expansion due to myelination). 
5.	Amongst mammals, anatomically modern humans show an unique pattern in which very slow musculoskeletal body growth is followed by a marked adolescent size/stature spurt. This pattern of growth contrasts with nonhuman primates that have a sustained fast juvenile growth with only a minor period of puberty acceleration. The existence of slow childhood growth in humans has been shown to date back to 160,000 BP. 
6.	Human children physiologically have a limited capacity to protect the brain from plasma glucose fluctuations and other metabolic disruptions. These can arise in adults, during prolonged strenuous exercise when skeletal muscle depletes plasma glucose, and produces other metabolic disruptions upon the brain (hypoxia, hyperthermia, dehydration and hyperammonemia). These are proportional to muscle mass.
7.	Children show specific adaptations to minimize such metabolic disturbances. (i) Due to slow body growth and resulting small body size, they have limited skeletal muscle mass. (ii) They show other adaptations such as an exercise specific preference for free fatty acid metabolism. (iii) While children are generally more active than adolescents and adults, they avoid physically prolonged intense exertion. 
8.	Childhood has a close relationship to high levels of energy provision and metabolic adaptations that support prolonged synaptic neurodevelopment. 
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Relevance of Porcine Stroke Models to Bridge the Gap from Pre-Clinical Findings to Clinical Implementation

Altres ajuts: This research is supported by grants from the Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III (ISCIII) to A.D. that was susceptible to be co-financed by FEDER funds, and a grant from Agència de Gestió d'Ajuts Universitaris i de Recerca to A.D. and to T.G. The group has received funding from "la Caixa Foundation" CI15-00009, from the European Institute of Innovation and Technology (EIT), which receives support from the European Union's Horizon 2020 research and innovation programme, from the Fundación para la Innovación y la Prospectiva en Salud en España (FIPSE) program 3594-18. M.M.-S. is a recipient of a PFIS contract FI19/00174.In the search of animal stroke models providing translational advantages for biomedical research, pigs are large mammals with interesting brain characteristics and wide social acceptance. Compared to rodents, pigs have human-like highly gyrencephalic brains. In addition, increasingly through phylogeny, animals have more sophisticated white matter connectivity; thus, ratios of white-to-gray matter in humans and pigs are higher than in rodents. Swine models provide the opportunity to study the effect of stroke with emphasis on white matter damage and neuroanatomical changes in connectivity, and their pathophysiological correlate. In addition, the subarachnoid space surrounding the swine brain resembles that of humans. This allows the accumulation of blood and clots in subarachnoid hemorrhage models mimicking the clinical condition. The clot accumulation has been reported to mediate pathological mechanisms known to contribute to infarct progression and final damage in stroke patients. Importantly, swine allows trustworthy tracking of brain damage evolution using the same non-invasive multimodal imaging sequences used in the clinical practice. Moreover, several models of comorbidities and pathologies usually found in stroke patients have recently been established in swine. We review here ischemic and hemorrhagic stroke models reported so far in pigs. The advantages and limitations of each model are also discussed

Human neuromaturation, juvenile extreme energy liability, and adult cognition/cooperation

Human childhood and adolescence is the period in which adult cognitive competences (including those that create the unique cooperativeness of humans) are acquired. It is also a period when neural development puts a juvenile’s survival at risk due to the high vulnerability of their brain to energy shortage. The brain of a 4 year-old human uses ≈50% of its total energy expenditure (TEE) (cf. adult ≈12%). This brain expensiveness is due to (1) the brain making up ≈6% of a 4 year-old body compared to 2% in an adult, and (2) increased energy metabolism that is ≈100% greater in the gray matter of a child than in an adult (a result of the extra costs of synaptic neuromaturation). The high absolute number of neurons in the human brain requires as part of learning a prolonged neurodevelopment. This refines inter- and intraarea neural networks so they become structured with economical “small world” connectivity attributes (such as hub organization and high cross-brain differentiation/integration). Once acquired, this connectivity enables highly complex adult cognitive capacities. Humans evolved as hunter-gatherers. Contemporary hunter-gatherers (and it is also likely Middle Paleolithic ones) pool high energy foods in an egalitarian manner that reliably supported mothers and juveniles with high energy intake. This type of sharing unique to humans protects against energy shortage happening to the immature brain. This cooperation that protects neuromaturation arises from adults having the capacity to communicate and evaluate social reputation, cognitive skills that exist as a result of extended neuromaturation. Human biology is therefore characterized by a presently overlooked bioenergetic-cognition loop (called here the “HEBE ring”) by which extended neuromaturation creates the cooperative abilities in adults that support juveniles through the potentially vulnerable period of the neurodevelopment needed to become such adults

Human metabolic adaptations and prolonged expensive neurodevelopment: A review

1.	After weaning, human hunter-gatherer juveniles receive substantial (≈3.5-7 MJ day^-1^), extended (≈15 years) and reliable (kin and nonkin food pooling) energy provision.
2.	The childhood (pediatric) and the adult human brain takes a very high share of both basal metabolic rate (BMR) (child: 50-70%; adult: ≈20%) and total energy expenditure (TEE) (child: 30-50%; adult: ≈10%).
3.	The pediatric brain for an extended period (≈4-9 years-of-age) consumes roughly 50% more energy than the adult one, and after this, continues during adolescence, at a high but declining rate. Within the brain, childhood cerebral gray matter has an even higher 1.9 to 2.2-fold increased energy consumption. 
4.	This metabolic expensiveness is due to (i) the high cost of synapse activation (74% of brain energy expenditure in humans), combined with (ii), a prolonged period of exuberance in synapse numbers (up to double the number present in adults). Cognitive development during this period associates with volumetric changes in gray matter (expansion and contraction due to metabolic related size alterations in glial cells and capillary vascularization), and in white matter (expansion due to myelination). 
5.	Amongst mammals, anatomically modern humans show an unique pattern in which very slow musculoskeletal body growth is followed by a marked adolescent size/stature spurt. This pattern of growth contrasts with nonhuman primates that have a sustained fast juvenile growth with only a minor period of puberty acceleration. The existence of slow childhood growth in humans has been shown to date back to 160,000 BP. 
6.	Human children physiologically have a limited capacity to protect the brain from plasma glucose fluctuations and other metabolic disruptions. These can arise in adults, during prolonged strenuous exercise when skeletal muscle depletes plasma glucose, and produces other metabolic disruptions upon the brain (hypoxia, hyperthermia, dehydration and hyperammonemia). These are proportional to muscle mass.
7.	Children show specific adaptations to minimize such metabolic disturbances. (i) Due to slow body growth and resulting small body size, they have limited skeletal muscle mass. (ii) They show other adaptations such as an exercise specific preference for free fatty acid metabolism. (iii) While children are generally more active than adolescents and adults, they avoid physically prolonged intense exertion. 
8.	Childhood has a close relationship to high levels of energy provision and metabolic adaptations that support prolonged synaptic neurodevelopment. 
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Glial cell mechanisms regulate alcohol sedation in Drosophila melanogaster

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol and functionally similar adult glial cells, especially astrocytes. Since previous research in mammals and flies has demonstrated that glia respond to alcohol administration, we hypothesized that glia are important regulators of alcohol-related behaviors. To pursue this, we characterized a pan-glial steroid-inducible GeneSwitch transgenic fly, which allows gene manipulation within glia during adulthood. We performed a targeted screen and manipulated genes that were known to be expressed within Drosophila glia and measured their alcohol sedation sensitivity using the ethanol sedation assay. We identified the genes Cysteine proteinase 1 (Cp1) and Tyramine decarboxylase 2 (Tdc2). Knocking down Cp1 in cortex glia, as well as all glia during adulthood, increased alcohol sedation sensitivity and may also enhance rapid tolerance development. We could not identify what pathway Cp1 was functioning within to mediate this response, suggesting that Cp1 may have a unique function within glia. Knockdown or overexpression of Tdc2 in glia increased or decreased alcohol sedation sensitivity, respectively. Tdc2 functions upstream of the vesicular monoamine transporter (VMAT) and the SNARE complex to regulate alcohol sedation. These results were specific to astrocytes, as well as all glia during adulthood. These results suggest that tyramine synthesis via Tdc2 and its release via vesicular exocytosis regulates alcohol sedation. Taken together, these results suggest that glia are important regulators of alcohol-related behaviors in flies. Interestingly, fly cortex glia and astrocytes are functionally similar to mammalian astrocytes, indicating that these results may be translatable to mammals

CaV2.2 Channels in Brain Development and Synaptic Plasticity

In the mammalian brain, presynaptic CaV2.2 channels play a pivotal role for synaptic transmission by mediating fast neurotransmitter exocytosis via influx of Ca2+ into the active zone at the presynaptic terminal. The distribution and activity of CaV2.2 channels at different synapses and maturity stages in the brain remains to be elucidated. In this study, I first show high levels of CaV2.2 channels in mouse cortex and hippocampus throughout development, persisting into adulthood. In contrast, CaV2.2 channels in the cerebellum and brain stem decreased as the brain matured. I thereafter assessed CaV2.2 channels during homeostatic synaptic plasticity, a compensatory form of homeostatic control preventing excessive or insufficient neuronal activity during which extensive active zone remodelling has been described. In this work I show that chronic silencing of neuronal activity in mature hippocampal cultures resulted in elevated presynaptic Ca2+ transients, mediated by a 30 % increase in CaV2.2 channel levels at the presynapse. Next, this work focussed on α2δ-1 subunits, important regulators of synaptic transmission and CaV2.2 channel abundance at the presynaptic membrane. Here, I show that α2δ-1- overexpression reduces the contribution of CaV2.2 channels to total Ca2+ flux without altering the amplitude of the Ca2+ transients. Finally, levels of endogenous α2δ-1 decreased during homeostatic synaptic plasticity, whereas the overexpression of α2δ-1 prevented homeostatic synaptic plasticity in hippocampal neurons. Together, this study reveals a key role for CaV2.2 channels and novel roles for α2δ-1 during plastic synaptic adaptation