RESUMEN
The amygdala is essential for generating emotional-affective behaviors. It consists of several nuclei with highly selective, elaborate functions. In particular, the central extended amygdala, consisting of the central amygdala (CEA) and the bed nucleus of the stria terminalis (BNST) is an essential component actively controlling efferent connections to downstream effectors like hypothalamus and brain stem. Both, CEA and BNST contain high amounts of different neuropeptides that significantly contribute to synaptic transmission. Among these, neuropeptide Y (NPY) has emerged as an important anxiolytic and fear-reducing neuromodulator. Here, we characterized the expression, connectivity and electrophysiological function of NPY and Y2 receptors within the CEA. We identified several NPY-expressing neuronal populations, including somatostatin- and calretinin-expressing neurons. Furthermore, in the main intercalated nucleus, NPY is expressed primarily in dopamine D1 receptor-expressing neurons but also in interspersed somatostatin-expressing neurons. Interestingly, NPY neurons did not co-localize with the Y2 receptor. Retrograde tract tracing experiments revealed that NPY neurons reciprocally connect the CEA and BNST. Functionally, the Y2 receptor agonist PYY3-36, reduced both, inhibitory as well as excitatory synaptic transmission in the centromedial amygdala (CEm). However, we also provide evidence that lack of NPY or Y2 receptors results in increased GABA release specifically at inhibitory synapses in the CEm. Taken together, our findings suggest that NPY expressed by distinct populations of neurons can modulate afferent and efferent projections of the CEA via presynaptic Y2 receptors located at inhibitory and excitatory synapses.
Asunto(s)
Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Potenciales Postsinápticos Excitadores , Potenciales Postsinápticos Inhibidores , Neuronas/fisiología , Neuropéptido Y/fisiología , Receptores de Neuropéptido Y/fisiología , Amígdala del Cerebelo/metabolismo , Animales , Calbindina 2/metabolismo , Núcleo Amigdalino Central/citología , Núcleo Amigdalino Central/metabolismo , Núcleo Amigdalino Central/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neuropéptido Y/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Neuropéptido Y/metabolismo , Núcleos Septales/citología , Núcleos Septales/metabolismo , Núcleos Septales/fisiología , Somatostatina/metabolismoRESUMEN
While anxiety disorders are the brain disorders with the highest prevalence and constitute a major burden for society, a considerable number of affected people are still treated insufficiently. Thus, in an attempt to identify potential new anxiolytic drug targets, neuropeptides have gained considerable attention in recent years. Compared to classical neurotransmitters they often have a regionally restricted distribution and may bind to several distinct receptor subtypes. Neuropeptide Y (NPY) is a highly conserved neuropeptide that is specifically concentrated in limbic brain areas and signals via at least 5 different G-protein-coupled receptors. It is involved in a variety of physiological processes including the modulation of emotional-affective behaviors. An anxiolytic and stress-reducing property of NPY is supported by many preclinical studies. Whether NPY may also interact with processing of learned fear and fear extinction is comparatively unknown. However, this has considerable relevance since pathological, inappropriate and generalized fear expression and impaired fear extinction are hallmarks of human post-traumatic stress disorder and a major reason for its treatment-resistance. Recent evidence from different laboratories emphasizes a fear-reducing role of NPY, predominantly mediated by exogenous NPY acting on Y1 receptors. Since a reduction of fear expression was also observed in Y1 receptor knockout mice, other Y receptors may be equally important. By acting on Y2 receptors, NPY promotes fear extinction and generates a long-term suppression of fear, two important preconditions that could support cognitive behavioral therapies in human patients. A similar effect has been demonstrated for the closely related pancreatic polypeptide (PP) when acting on Y4 receptors. Preliminary evidence suggests that NPY modulates fear in particular by activation of Y1 and Y2 receptors in the basolateral and central amygdala, respectively. In the basolateral amygdala, NPY signaling activates inhibitory G protein-coupled inwardly-rectifying potassium channels or suppresses hyperpolarization-induced I(h) currents in a Y1 receptor-dependent fashion, favoring a general suppression of neuronal activity. A more complex situation has been described for the central extended amygdala, where NPY reduces the frequency of inhibitory and excitatory postsynaptic currents. In particular the inhibition of long-range central amygdala output neurons may result in a Y2 receptor-dependent suppression of fear. The role of NPY in processes of learned fear and fear extinction is, however, only beginning to emerge, and multiple questions regarding the relevance of endogenous NPY and different receptor subtypes remain elusive. Y2 receptors may be of particular interest for future studies, since they are the most prominent Y receptor subtype in the human brain and thus among the most promising therapeutic drug targets when translating preclinical evidence to potential new therapies for human anxiety disorders.
Asunto(s)
Encéfalo/metabolismo , Condicionamiento Psicológico/fisiología , Miedo/fisiología , Neuronas/metabolismo , Neuropéptido Y/metabolismo , Animales , Humanos , Neuropéptidos/metabolismoRESUMEN
The amygdala is fundamental for associative fear and extinction learning. Recently, also the central nucleus of the amygdala (CEA) has emerged as a site of plasticity actively controlling efferent connections to downstream effector brain areas. Although synaptic transmission is primarily mediated by glutamate and GABA, neuropeptides critically influence the overall response. While neuropeptide Y (NPY) acting via postsynaptic Y1 receptors exerts an important anxiolytic and fear-reducing action, the role of the predominantly presynaptic Y2 receptors is less defined. To investigate the role of Y2 receptors in the CEA we employed viral-vector mediated over-expression of the Y2 selective agonist NPY3-36 in fear conditioning and extinction experiments. NPY3-36 over-expression in the CEA resulted in reduced fear expression during fear acquisition and recall. Interestingly, this effect was blocked by intraperitoneal injection of a brain-penetrant Y2 receptor antagonist. Furthermore, over-expression of NPY3-36 in the CEA also reduced fear expression during fear extinction of CS-induced but not context-related fear. Again, fear extinction appeared delayed by peripheral injection of a Y2 receptor antagonist JNJ-31020028. Importantly, mice with over-expression of NPY3-36 in the CEA also displayed reduced spontaneous recovery and reinstatement, suggesting that Y2 receptor activation supports a permanent suppression of fear. Local deletion of Y2 receptors in the CEA, on the other hand, increased the expression of CS-induced freezing during fear recall and fear extinction. Thus, NPY inhibits fear learning and promotes cued extinction by reducing fear expression also via activation of presynaptic Y2 receptors on CEA neurons.
Asunto(s)
Núcleo Amigdalino Central/metabolismo , Miedo/fisiología , Receptores de Neuropéptido Y/metabolismo , Animales , Benzamidas/administración & dosificación , Núcleo Amigdalino Central/efectos de los fármacos , Fármacos del Sistema Nervioso Central/administración & dosificación , Señales (Psicología) , Dependovirus/genética , Extinción Psicológica/efectos de los fármacos , Extinción Psicológica/fisiología , Miedo/efectos de los fármacos , Vectores Genéticos , Masculino , Recuerdo Mental/efectos de los fármacos , Recuerdo Mental/fisiología , Ratones Endogámicos C57BL , Ratones Noqueados , Neuropéptido Y/administración & dosificación , Neuropéptido Y/genética , Neuropéptido Y/metabolismo , Pruebas Neuropsicológicas , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Piperazinas/administración & dosificación , Receptores de Neuropéptido Y/agonistas , Receptores de Neuropéptido Y/antagonistas & inhibidores , Receptores de Neuropéptido Y/genéticaRESUMEN
Phenomenologically important quantum dissipative processes include blackbody friction (an atom absorbs counterpropagating blueshifted photons and spontaneously emits them in all directions, losing kinetic energy) and noncontact van der Waals friction (in the vicinity of a dielectric surface, the mirror charges of the constituent particles inside the surface experience drag, slowing the atom). The theoretical predictions for these processes are modified upon a rigorous quantum electrodynamic treatment, which shows that the one-loop "correction" yields the dominant contribution to the off-resonant, gauge-invariant, imaginary part of the atom's polarizability at room temperature, for typical atom-surface interactions. The tree-level contribution to the polarizability dominates at high temperature.
RESUMEN
Mushrooms have, repeatedly, been shown to contain nicotine. Speculation about the source of contamination has been widespread, however the source of nicotine remains unknown. Previous studies indicate that putrescine, an intermediate in nicotine biosynthesis, can be formed in mushrooms, which might be metabolised to form nicotine. Thus, endogenous formation may be a possible cause for elevated nicotine levels in mushrooms. We present evidence from the literature that may support this hypothesis.
Asunto(s)
Agaricales/metabolismo , Aminas Biogénicas/metabolismo , Nicotina/biosíntesis , Agaricales/química , Aminas Biogénicas/análisis , Nicotina/análisis , Putrescina/análisis , Putrescina/metabolismoRESUMEN
The thermal friction force acting on an atom moving relative to a thermal photon bath is known to be proportional to an integral over the imaginary part of the frequency-dependent atomic (dipole) polarizability. Using a numerical approach, we find that blackbody friction on atoms either in dilute environments or in hot ovens is larger than previously thought by orders of magnitude. This enhancement is due to far off-resonant driving of transitions by low-frequency thermal radiation. At typical temperatures, the blackbody radiation maximum lies far below the atomic transition wavelengths. Surprisingly, due to the finite lifetime of atomic levels, which gives rise to Lorentzian line profiles, far off-resonant excitation leads to the dominant contribution for blackbody friction.
RESUMEN
The helium pair potential was computed including relativistic and quantum electrodynamics contributions as well as improved accuracy adiabatic ones. Accurate asymptotic expansions were used for large distances R. Error estimates show that the present potential is more accurate than any published to date. The computed dissociation energy and the average R for the (4)He(2) bound state are 1.62+/-0.03 mK and 47.1+/-0.5 A. These values can be compared with the measured ones: 1.1(-0.2)(+0.3) mK and 52+/-4 A [R. E. Grisenti, Phys. Rev. Lett. 85, 2284 (2000)].
RESUMEN
An automated HPLC method with postcolumn derivatization is described for the determination of aflatoxins B1, B2, G1 and G2 after an immunoaffinity column clean-up. It can be used for the determination of aflatoxins in a variety of foodstuffs such as nuts, nut-like products (pistachios, almonds, etc.) and dried fruit. The aflatoxins are extracted with methanol-water, followed by a filtration step. Dilution of the extract, mixing, immunoaffinity column clean-up, elution of the aflatoxins and optional on-line HPLC are performed by an automatic work station (Zymark BenchMate). The subsequent HPLC analysis includes a postcolumn derivatization step with iodine solution and fluorimetric detection. The method compared well with manual techniques and another automated method.
Asunto(s)
Aflatoxinas/análisis , Cromatografía Líquida de Alta Presión/métodos , Contaminación de Alimentos/análisis , Automatización , Cromatografía de Afinidad/métodos , Cromatografía Líquida de Alta Presión/instrumentaciónRESUMEN
When quantified by HPGC-ECD and HPGC-NCI-SIM commercially available standards of the insecticide Toxaphene show different detector responses, primarily depending on the percentage of chlorine in the mixtures. To obtain accurate results, residues of Toxaphene in environmental samples should be quantified by using a standard with a similar or nearly similar detector response. If this is not possible, any standard may be used but the results of the samples must be corrected afterwards. By comparing different integration methods, it can be seen that the best results are obtained by integrating as many single-peak areas as possible. Quantification by integration of the bulge formed by raising the baseline, which can be observed in many gas chromatograms of Toxaphene standards, should be avoided because this hump is caused by degradation of chlorobornanes under higher temperatures. The extent of this bulge depends both on temperature and the percentage of chlorine, the latter being generally lower in the samples as a result of transformation processes under environmental conditions. Therefore integration of the bulge or the whole area leads to lower results.