Dendritic size of pyramidal neurons differs among mouse cortical regions

12 pages, 7 figures, 3 tables.-- PMID: 16195469 [PubMed].-- Available online Sep 29, 2005.Neocortical circuits share anatomical and physiological similarities among different species and cortical areas. Because of this, a ‘canonical’ cortical microcircuit could form the functional unit of the neocortex and perform the same basic computation on different types of inputs. However, variations in pyramidal cell structure between different primate cortical areas exist, indicating that different cortical areas could be built out of different neuronal cell types. In the present study, we have investigated the dendritic architecture of 90 layer II/III pyramidal neurons located in different cortical regions along a rostrocaudal axis in the mouse neocortex, using, for the first time, a blind multidimensional analysis of over 150 morphological variables, rather than evaluating along single morphological parameters. These cortical regions included the secondary motor cortex (M2), the secondary somatosensory cortex (S2), and the lateral secondary visual cortex and association temporal cortex (V2L/TeA). Confirming earlier primate studies, we find that basal dendritic morphologies are characteristically different between different cortical regions. In addition, we demonstrate that these differences are not related to the physical location of the neuron and cannot be easily explained assuming rostrocaudal gradients within the cortex. Our data suggest that each cortical region is built with specific neuronal components.R.B.-P. thanks the ‘Comunidad de Madrid’ (01/0782/2000) and I.B.-Y. the MEC (AP2001-0671) for support. J.D. is supported by the Spanish Ministry of Education and Science (BFI2003-02745) and the Comunidad de Madrid (08.5/0027/2001.1). R.Y. thanks the NEI (EY11787) and the John Merck Fund for support and the Cajal Institute for hosting him as a visiting professor.Peer reviewe

Capítulo 2. El cerebro adicto

Este capítulo trata de explicar, de una manera muy sencilla, las razones por las que se ingieren alimentos, más allá de las puramente nutritivas. Una de estas razones es que los alimentos altamente palatables producen la activación de nuestro sistema mesocorticolímbico cerebral, anticipando la recompensa que sentiremos y produciendo la propia sensación de placer. Entre los neurotransmisores principales encargados de esta comunicación cerebral se encuentra la dopamina y las regiones cerebrales principales del sistema son: Área Tegmental Ventral (VTA), Núcleo Accumbens (NAc), Corteza Prefrontal e Hipocampo. Modificaciones en el circuito cerebral de recompensa pueden ser responsables tanto de la obesidad como de las adicciones a otras sustancias (drogas de abuso)

The role of adenosine receptors in psychostimulant addiction

Adenosine receptors (AR) are a family of G-protein coupled receptors, comprised of four members, named A1, A2A, A2B, and A3receptors, found widely distributed in almost all human body tissues and organs. To date, they are known to participate in a large variety of physiopathological responses, which include vasodilation, pain, and inflammation. In particular, in the central nervous system (CNS), adenosine acts as a neuromodulator, exerting different functions depending on the type of AR and consequent cellular signaling involved. In terms of molecular pathways and second messengers involved, A1and A3receptors inhibit adenylyl cyclase (AC), through Gi/oproteins, while A2Aand A2Breceptors stimulate it through Gs proteins. In the CNS, A1receptors are widely distributed in the cortex, hippocampus, and cerebellum, A2Areceptors are localized mainly in the striatum and olfactory bulb, while A2Band A3receptors are found at low levels of expression. In addition, AR are able to form heteromers, both among themselves (e.g., A1/A2A), as well as with other subtypes (e.g., A2A/D2), opening a whole range of possibilities in the field of the pharmacology of AR. Nowadays, we know that adenosine, by acting on adenosine A1and A2Areceptors, is known to antagonistically modulate dopaminergic neurotransmission and therefore reward systems, being A1receptors colocalized in heteromeric complexes with D1receptors, and A2Areceptors with D2receptors. This review documents the present state of knowledge of the contribution of AR, particularly A1and A2A, to psychostimulants-mediated effects, including locomotor activity, discrimination, seeking and reward, and discuss their therapeutic relevance to psychostimulant addiction. Studies presented in this review reinforce the potential of A1agonists as an effective strategy to counteract psychostimulant-induced effects. Furthermore, different experimental data support the hypothesis that A2A/D2heterodimers are partly responsible for the psychomotor and reinforcing effects of psychostimulant drugs, such as cocaine and amphetamine, and the stimulation of A2Areceptor is proposed as a potential therapeutic target for the treatment of drug addiction. The overall analysis of presented data provide evidence that excitatory modulation of A1and A2Areceptors constitute promising tools to counteract psychostimulants addiction

Dendritic Size of Pyramidal Neurons Differs among Mouse Cortical Regions

Neocortical circuits share anatomical and physiological similarities among different species and cortical areas. Because of this, a ‘canonical ’ cortical microcircuit could form the functional unit of the neocortex and perform the same basic computation on different types of inputs. However, variations in pyramidal cell structure between different primate cortical areas exist, indicating that different cortical areas could be built out of different neuronal cell types. In the present study, we have investigated the dendritic architecture of 90 layer II/III pyramidal neurons located in different cortical regions along a rostrocaudal axis in the mouse neocortex, using, for the first time, a blind multidimensional analysis of over 150 morphological variables, rather than evaluating along single morphological parameters. These cortical regions included the secondary motor cortex (M2), the secondary somatosensory cortex (S2), and the lateral secondary visual cortex and association temporal cortex (V2L / TeA). Confirming earlier primate studies, we find that basal dendritic morphologies are characteristically different between different cortical regions. In addition, we demonstrate that these differences are not related to the physical location of the neuron and cannot be easily explained assuming rostrocaudal gradients within the cortex. Our data suggest that each cortical region is built with specific neuronal components

The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background

© 2013 The Author. Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds.Peer Reviewe

Morphine self-administration effects on the structure of cortical pyramidal cells in addiction-resistant rats

12 pages, 4 figures, 4 tables.-- PMID: 18657522 [PubMed].-- Printed version published Sep 16, 2008.Repeated administration of drugs of abuse is thought to induce a variety of persistent changes in both behavior and brain morphology, including modifications of neurons from the brain regions involved in addiction. We have studied the morphology of the basal dendritic arbor of cortical pyramidal neurons in addiction-resistant Fischer 344 strain rats that self-administered morphine. Pyramidal neurons in the prelimbic and motor cortex were intracellularly injected with Lucifer Yellow in fixed tissue and they were reconstructed in three dimensions using Neurolucida software. Morphine self-administration did not produce significant changes in the structure of the dendritic arbors or in the spine density of pyramidal neurons in either the prelimbic or motor cortex of F344 rats. Moreover, pyramidal cell morphology did not differ in these two cortical areas in saline self-administered animals. However, when the structure of these cortical pyramidal cells from Fischer 344 rats was compared with that previously reported in addiction-prone Lewis rats in the same cortical areas, significant morphological differences were found between both strains. Indeed, these differences were not only observed following morphine self-administration but also in saline self-administered control animals. We suggest that strain differences in the structure of pyramidal cells in certain cortical areas might represent an anatomical substrate for the distinct vulnerability to the reinforcing effects of morphine exhibited by Fischer 344 and Lewis rats in operant self-administration paradigms.Morphine sulphate was kindly provided by the “Dirección General de Estupefacientes” (Spain). This work was supported by the “Ministerio de Educación y Ciencia” (grants BFI 2003–02745, BFU2006–13395 and “Genómica y Proteómica” GEN2003–20651-C06–06 to J DeF) and by the “Fondo de Inversiones Sanitarias” FIS01–05–01; the “Plan Nacional sobre Drogas” PNSD2000–2003; the “Comunidad Autónoma de Madrid” CAM08.8/0010.1/2003, “Plan de Promoción de la Investigación en la UNED” and “Salud y Farmacia” SAF2007–64890 grants to EA. IB-Y is a “Juan de la Cierva” postdoctoral fellow of the Ministry of Science and Technology.Peer reviewe

On-demand Hydrophobic Drug Release Based on Microwaveresponsive Graphene Hydrogel Scaffolds

Electromagnetically driven drug delivery systems stand out among stimulus-responsive materials due to their ability to release cargo on demand by remote stimulation, such as light, near infrared (NIR) or microwave (MW) radiation. MW-responsive soft materials, such as hydrogels, generally operate at 2.45 GHz frequencies, which usually involves rapid overheating of the scaffold and may affect tissue surrounding the target location. In contrast, 915 MHz MW penetrate deeper tissues and are less prone to induce rapid overheating. In order to circumvent these limitations, we present here for the first time a graphene-based hydrogel that is responsive to MW irradiation of ν = 915 MHz. This system is a candidate soft scaffold to deliver a model hydrophobic drug. The graphene present in the hydrogel acts as a heat-sink and avoids overheating of the scaffold upon MW irradiation. In addition, the microwave trigger stimulates the in vitro delivery of the model drug, thus suggesting a remote and deeppenetrating means to deliver a drug from a delivery reservoir. Moreover, the MW-triggered release of drug was observed to be enhanced under acidic conditions, where the swelling state is maximum due to the swelling-induced pH-responsiveness of the hydrogel. The hybrid composite described here is a harmless means to deliver remotely a hydrophobic drug on demand with a MW source of 915 MHz. Potential uses in biomedical applications were evaluated by cytotoxicity tests

Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice

Addiction involves long-lasting maladaptive changes including development of disruptive drug-stimuli associations. Nicotine-induced neuroplasticity underlies the development of tobacco addiction but also, in regions such as the hippocampus, the ability of this drug to enhance cognitive capabilities. Here, we propose that the genetic locus of susceptibility to nicotine addiction, the CHRNA5/A3/B4 gene cluster, encoding the α5, α3 and β4 subunits of the nicotinic acetylcholine receptors (nAChRs), may influence nicotine-induced neuroadaptations. We have used transgenic mice overexpressing the human cluster (TgCHRNA5/A3/B4) to investigate hippocampal structure and function in genetically susceptible individuals. TgCHRNA5/A3/B4 mice presented a marked reduction in the dendrite complexity of CA1 hippocampal pyramidal neurons along with an increased dendritic spine density. In addition, TgCHRNA5/A3/B4 exhibited increased VGLUT1/VGAT ratio in the CA1 region, suggesting an excitatory/inhibitory imbalance. These hippocampal alterations were accompanied by a significant impairment in short-term novelty recognition memory. Interestingly, chronic infusion of nicotine (3.25 mg/kg/d for 7 d) was able to rescue the reduced dendritic complexity, the excitatory/inhibitory imbalance and the cognitive impairment in TgCHRNA5/A3/B4. Our results suggest that chronic nicotine treatment may represent a compensatory strategy in individuals with altered expression of the CHRNA5/A3/B4 region

Cortical microarchitecture alterations in Ts65Dn mice, an animal model for Down Syndrome: Impact of environmental enrichment | Alteraciones de la microarquitectura de la corteza cerebral en el ratón Ts65Dn, un modelo murino de síndrome de Down: Efectos del enriquecimiento ambiental

Down syndrome (DS) is the most common genetic disorder associated with mental retardation, affecting 1 in 1000 newborn children in Europe. Studies of DS population provide a rare opportunity to examine relationships between cognition, genotype and brain neurobiology, allowing comparisons across these different levels of analysis. The crucial question is to define how do excess of normal gene products in interaction with the environment, direct and constrain neural maturation and how does this maldevelopment translate into mind and behavior. Although mental retardation likely involves anatomical, chemical and neurophysiological brain abnormalities, the mechanisms by which subnormal intelligence during development arise from these abnormalities are difficult to discern. Dendritic abnormalities are the most consistent anatomical correlates of mental retardation. Earliest descriptions of dendritic pathology in DS included dendritic spine dysgenesis, and dendritic anomalies involving branches. Dendritic abnormalities appear to have specific consequences in the pathogenesis and evolution of DS brains, which correlate to some extent with the cognitive profile. The cortical microarchitecture of animal models and the impact of environmental enrichment on the phenotype, centered in dendritic abnormalities and plasticity, is analyzed.Peer Reviewe

Relationship between exclusive breastfeeding and brain-derived neurotrophic factor in children.

ObjectiveA positive relationship between breastfeeding and brain-derived neurotrophic factor (BDNF) in infants has been suggested due to the presence of BDNF in human milk. This study aimed to determine the relationship between exclusive breastfeeding and BDNF serum levels in Spanish schoolchildren.MethodsA cross-sectional analysis including 202 schoolchildren, aged eight to 11 years, from Cuenca, Spain, was conducted. Information on sociodemographic and anthropometric variables, sexual maturation, birth weight and exclusive breastfeeding ('no exclusive breastfeeding', and exclusive breastfeeding for ≤6 and >6 months), and BDNF serum levels using an ELISA method were obtained. Covariance analyses (ANCOVA) were conducted to examine the relationship between serological BDNF and exclusive breastfeeding after controlling for potential confounders.ResultsANCOVA models showed no significant differences in BDNF levels between children who were exclusively breastfed for more than six months versus those who were not (p > 0.05). No significant differences were observed by age group (eight to nine years versus 10 to 11 years; p > 0.05). Additionally, no clear negative trend in BDNF serum levels according to sexual maturation categories was found (p > 0.05).ConclusionThese findings suggest that exclusive breastfeeding does not have a significant positive association on BDNF from eight to 11 years, since children who were exclusively breastfed did not have significantly higher BDNF levels than those who were not exclusively breastfed. Likewise, BDNF levels were not found to be negatively affected by hormonal development. Future research should examine the influence of exclusive breastfeeding on BDNF over the different developmental stages