Introductory Chapter: Feed Your Mind - How Does Nutrition Modulate Brain Function throughout Life?

Nutrition is an environmental factor modulating physiology throughout life and especially brain function. Nutrients in the brain can either fuel brain cells, contribute to tissue architecture, or initiate signaling pathways through their derivatives. Nutrients ultimately participate in brain development, cognitive and emotional behaviors, and can influence the susceptibility to develop brain pathologies. This book is a selection of current research on the impact of diet on brain function. Chapters include the role of lipids and glucose on the brain, nutrition and autophagy, and consequences of enteral feeding on brain-gut interactions. Taken together, this book targets all scientists, clinicians, teachers, and students eager to learn more about the impact of nutrition on brain function

The Addiction-Susceptibility TaqIA/Ankk1 Controls Reward and Metabolism Through D2 Receptor-Expressing Neurons

Background: A large body of evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the TaqIA polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the ankyrin repeat and kinase domain containing 1 kinase (Ankk1) near the dopamine D2 receptor (D2R) gene. Homozygous expression of the A1 allele correlates with a 30% to 40% reduction of striatal D2R, a typical feature of addiction, overeating, and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior are unknown. Methods: Here, we used transgenic and viral-mediated strategies to reveal the role of Ankk1 in the regulation of activity and functions of the striatum. Results: We found that Ankk1 is preferentially enriched in striatal D2R-expressing neurons and that Ankk1 loss of function in the dorsal and ventral striatum leads to alteration in learning, impulsivity, and flexibility resembling endophenotypes described in A1 carriers. We also observed an unsuspected role of Ankk1 in striatal D2R-expressing neurons of the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with or without the A1 allele. Conclusions: Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for Ankk1 in the regulation of body metabolism.Altérations du système de récompense dans l'anorexie mentaleRole du biostatus en acides gras polyinsaturés dans les troubles de contrôle exécuti

In silico Hierarchical Clustering of Neuronal Populations in the Rat Ventral Tegmental Area Based on Extracellular Electrophysiological Properties.

The ventral tegmental area (VTA) is a heterogeneous brain region, containing different neuronal populations. During recordings, electrophysiological characteristics are classically used to distinguish the different populations. However, the VTA is also considered as a region harboring neurons with heterogeneous properties. In the present study, we aimed to classify VTA neurons using approaches, in an attempt to determine if homogeneous populations could be extracted. Thus, we recorded 291 VTA neurons during extracellular recordings in anesthetized rats. Initially, 22 neurons with high firing rates (>10 Hz) and short-lasting action potentials (AP) were considered as a separate subpopulation, in light of previous studies. To segregate the remaining 269 neurons, presumably dopaminergic (DA), we performed analyses, using a combination of different electrophysiological parameters. These parameters included: (1) firing rate; (2) firing rate coefficient of variation (CV); (3) percentage of spikes in a burst; (4) AP duration; (5) Δt duration (i.e., time from initiation of depolarization until end of repolarization); and (6) presence of a notched AP waveform. Unsupervised hierarchical clustering revealed two neuronal populations that differed in their bursting activities. The largest population presented low bursting activities (17.5%). Within non-high-firing neurons, a large heterogeneity was noted concerning AP characteristics. In conclusion, this analysis based on conventional electrophysiological criteria clustered two subpopulations of putative DA VTA neurons that are distinguishable by their firing patterns (firing rates and bursting activities) but not their AP properties

Chapter Dietary Omega-6/Omega-3 and Endocannabinoids: Implications for Brain Health and Diseases

In this study, we compare two economic models of urban gardening in Ljubljana, Slovenia. First is an avoided costs model (ACM) and the second one is a business model (BM). Comparison is made to exemplify the main economic differences between the two models. The difference is that producers under the BM sell surplus products, which is not the case under the ACM. The main aim of this study is to present an analysis of the phenomenon of urban gardening as a BM for small family home or allotment gardens. The survey was performed through Internet questionnaires and in some cases also with on-site interviews. Totally 127 urban gardeners from Ljubljana municipality participated in the research. The average ACM urban gardeners had on 1 m2 revenue of 4.86 EUR/m2, costs of 1.48 EUR/m2 and gross margin (savings) of 3.38 EUR/m2. Altogether, ACM brings savings of approximately 462.7 EUR per average size garden (136.69 m2) or 203 EUR per median size garden (60 m2) to the average gardener. The average BM gardener sold to the wholesale company approximately 107.0 kg of vegetables per year from 32.48 m2 of production area for an average retail price of 1.46 EUR/kg and earning revenue of 156.44 EUR/year. Costs were approximately 21.27 EUR/year. Therefore, the gross margin or earning from surpluses sold was approximately 135.17 EUR/year for the average BM gardener, which was 4.29 EUR/m2 or 1.26 EUR/kg of produce. The study offers evidence that the ACM can be upgraded with the BM. For example, if a family of two retired members have an average garden of 136 m2, they can produce vegetables for four people. Consequent surpluses for two family members can be sold for extra money. The BM should be more promoted among urban gardeners as it can offer additional income and in certain cases, when a hobby becomes a profession, also a full-time job

Nutritional n-3 PUFA Deficiency Abolishes Endocannabinoid Gating of Hippocampal Long-Term Potentiation

International audienceMaternal n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, is critical during perinatal brain development. How early postnatal n-3 PUFA deficiency impacts on hippocampal synaptic plasticity is mostly unknown. Here we compared activity-dependent plasticity at excitatory and inhibitory synapses in the CA1 region of the hippocampus in weaned pups whose mothers were fed with an n-3 PUFA-balanced or n-3 PUFA-deficient diet. Normally, endogenous cannabinoids (eCB) produced by the post-synapse dually control network activity by mediating the long-term depression of inhibitory inputs (iLTD) and positively gating NMDAR-dependent long-term potentiation (LTP) of excitatory inputs. We found that both iLTD and LTP were impaired in n-3 PUFA-deficient mice. Pharmacological dissection of the underlying mechanism revealed that impairment of NMDAR-dependent LTP was causally linked to and attributable to the ablation of eCB-mediated iLTD and associated to disinhibitory gating of excitatory synapses. The data shed new light on how n-3 PUFAs shape synaptic activity in the hippocampus and provide a new synaptic substrate to the cognitive impairments associated with perinatal n-3 deficiency

Neuronal morphology and synaptic plasticity in the hippocampus of vitamin A deficient rats

Vitamin A (retinol) and related retinoids are micronutrients provided by food. Retinol derivatives are growth factors important for development, cell differentiation and tissue homeostasis, especially in the brain. Objective: The hippocampus is a pivotal brain structure for learning and memory and hippocampal-dependent memory is highly sensitive to retinoids action. However, the underlying mechanisms are still unclear. In this study, we characterized the impact of vitamin A deficiency on memory and neuronal plasticity, focusing on the CA1 region of the hippocampus in rats. Methods: Weaned male Wistar rats were fed a control (5 UI/g) or deficient vitamin A diet (0 UI/g) for 10 weeks. The effect of vitamin A supplementation (20 UI/g) for 3 weeks was also tested. Memory performances were assessed in the Y-maze (n = 24–30/group), retinoic acid levels were measured (LC-MS/MS) in the serum and in the hippocampus (n = 5/group), CA1 neuronal architecture was analyzed with Golgi staining (n = 17–20 neurons/group) and electrophysiological patch-clamp recordings were performed on hippocampal brain slices (n = 6–11/group). Results: Vitamin A deficiency from weaning significantly lowered hippocampal levels of retinoic acid, reduced dendritic length and branching of CA1 pyramidal neurons and decreased spontaneous glutamatergic synaptic events and synaptic plasticity. When replenishment with moderate dose of dietary vitamin A for 3 weeks was done, most of the synaptic and morphological alterations were absent. Conclusion: This study provides new mechanistic insight to understand the critical role of retinoic acid in hippocampal function

Vulnerability of the nucleus accumbens neuronal network to developmental n-3 PUFA deficiency: consequences on the reward and motivation system

National audienceVarious, though distinct psychiatric disorders, such as Schizophrenia, bipolar disorder or major depression are associated with a dysfunction of the reward system linked to an alteration of dopamine transmission. Furthermore, these pathologies are also accompanied by changes in lipid metabolism and in particular a decrease in the brain content n-3 polyunsaturated fatty acid (PUFA) in the nervous system. However, the implication of brain lipid composition in the etiology of psychiatric endophenotypes has been overlooked. The aim of this study was to investigate a potential causal link between n-3 PUFA deficiency and deficits in reward processing. Using operant conditioning tasks in mice, we showed that developmental n-3 PUFA deficiency leads to a selective motivational deficit at adulthood that is reversed by n-3 PUFA supplementation starting at birth. In parallel, we showed that n-3 PUFA deficiency leads to alterations in electrophysiological properties of medium spiny neurons (MSNs) in the nucleus accumbens, main actors for motivational processes. MSNs from the direct pathway (dMSNs) displayed a decrease in excitability paralleled with an increase of inhibitory input onto these neurons. Using pharmacogenetic and transgenic approaches, we showed that 1) alterations in dMSNs directly results from increased inhibitory input from MSNs of the indirect pathway (iMSNs), called lateral inhibition and 2) rescuing appropriate PUFA levels in D2R-expressing neurons selectively (including iMSNs), was sufficient to reverse both alterations in electrophysiological properties of dMSNs and motivational deficit observed in n-3 PUFA deficient mice

Intracellular Properties of Deep-Layer Pyramidal Neurons in Frontal Eye Field of Macaque Monkeys

International audienceAlthough many details remain unknown, several positive statements can be made about the laminar distribution of primate frontal eye field (FEF) neurons with different physiological properties. Most certainly, pyramidal neurons in the deep layer of FEF that project to the brainstem carry movement and fixation signals but clear evidence also support that at least some deep-layer pyramidal neurons projecting to the superior colliculus carry visual responses. Thus, deep-layer neurons in FEF are functionally heterogeneous. Despite the useful functional distinctions between neuronal responses in vivo, the underlying existence of distinct cell types remain uncertain, mostly due to methodological limitations of extracellular recordings in awake behaving primates. To substantiate the functionally defined cell types encountered in the deep layer of FEF, we measured the biophysical properties of pyramidal neurons recorded intracellularly in brain slices issued from macaque monkey biopsies. Here, we found that biophysical properties recorded in vitro permit us to distinguish two main subtypes of regular-spiking neurons, with, respectively, low-resistance and low excitability vs. high-resistance and strong excitability. These results provide useful constraints for cognitive models of visual attention and saccade production by indicating that at least two distinct populations of deep-layer neurons exist

Impact of dietary vitamin A on striatal function in adult rats

The striatum is a brain structure involved in the control of voluntary movement. Striatum contains high amounts of retinoic acid, the active metabolite of vitamin A, as well as retinoid receptors, RARβ and RXRγ. Previous studies revealed that disruption of retinoid signaling initiated during development is deleterious for striatal physiology and related motor functions. However, the alteration of retinoid signaling, and the importance of vitamin A supply during adulthood on striatal physiology and function has never been established. In the present study, we investigated the impact of vitamin A supply on striatal function. Adult Sprague Dawley rats were fed with three specific diets, either sub-deficient, sufficient, or enriched in vitamin A (0.4, 5 and 20 international units (IU) of retinol per g of diet, respectively) for 6 months. We first validated that vitamin A sub-deficient diet in adult rats constitutes a physiological model of retinoid signaling reduction in the striatum. We then revealed subtle alterations of fine motor skills in sub-deficient rats using a new behavioral apparatus specifically designed to test forepaw reach-and-grasp skills relying on striatal function. Finally, we showed using qPCR analysis and immunofluorescence that the striatal dopaminergic system per se was not affected by vitamin A sub-deficiency at adult age. Rather, cholinergic synthesis in the striatum and μ-opioid receptor expression in striosomes sub-territories were the most affected by vitamin A sub-deficiency starting at adulthood. Taken together these results revealed that retinoid signaling alteration at adulthood is associated with Amotor learning deficits together with discrete neurobiological alterations in the striatum