RESUMEN
Egg laying in the nematode worm Caenorhabditis elegans is a two-state behavior modulated by internal and external sensory input. We have previously shown that homeostatic feedback of embryo accumulation in the uterus regulates bursting activity of the serotonergic HSN command neurons that sustains the egg-laying active state. How sensory feedback of egg release signals to terminate the egg-laying active state is less understood. We find that Gαo, a conserved Pertussis Toxin-sensitive G protein, signals within HSN to inhibit egg-laying circuit activity and prevent entry into the active state. Gαo signaling hyperpolarizes HSN, reducing HSN Ca2+ activity and input onto the postsynaptic vulval muscles. Loss of inhibitory Gαo signaling uncouples presynaptic HSN activity from a postsynaptic, stretch-dependent homeostat, causing precocious entry into the egg-laying active state when only a few eggs are present in the uterus. Feedback of vulval opening and egg release activates the uv1 neuroendocrine cells which release NLP-7 neuropeptides which signal to inhibit egg laying through Gαo-independent mechanisms in the HSNs and Gαo-dependent mechanisms in cells other than the HSNs. Thus, neuropeptide and inhibitory Gαo signaling maintain a bi-stable state of electrical excitability that dynamically controls circuit activity in response to both external and internal sensory input to drive a two-state behavior output.
Asunto(s)
Potenciales de Acción , Proteínas de Caenorhabditis elegans/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Neuronas/metabolismo , Oviposición , Animales , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Calcio/metabolismo , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Contracción Muscular , Neuronas/fisiología , Neuropéptidos/genética , Neuropéptidos/metabolismo , Transducción de Señal , Vulva/citología , Vulva/inervación , Vulva/fisiologíaRESUMEN
Water is a renewable resource but yet finite. Its sustainable usage and the maintenance of a good quality are essential for an intact environment, human life and a stable economy. Emerging technologies aim for a continuous monitoring of water quality, overcoming periodic analytical sampling, and providing information on the current state of inshore waters in real time. So does the here presented cell-based sensor system which uses RLC-18 cells (rat liver cells) as the detection layer for the detection of water pollutants. The electrical read-out of the system, cellular metabolism, oxygen consumption and morphological integrity detects small changes in the water quality and indicates a possible physiological damage caused. A generalized functional linear model was implemented in order to regress the chemicals present in the sample on the electrical read-out. The chosen environmental pollutants to test the system were chlorpyrifos, an organophosphate pesticide, and tetrabromobisphenol A, a flame retardant. Each chemical gives a very characteristic response, but the toxicity is mitigated if both chemicals are present at once. This will focus our attention on the statistical approach which is able to discriminate between these pollutants.
Asunto(s)
Técnicas Biosensibles/instrumentación , Cloropirifos/análisis , Retardadores de Llama/análisis , Plaguicidas/análisis , Bifenilos Polibrominados/análisis , Contaminantes Químicos del Agua/análisis , Calidad del Agua , Animales , Línea Celular , Cloropirifos/toxicidad , Diseño de Equipo , Retardadores de Llama/toxicidad , Dispositivos Laboratorio en un Chip , Hígado/citología , Hígado/efectos de los fármacos , Hígado/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Plaguicidas/toxicidad , Bifenilos Polibrominados/toxicidad , Ratas , Contaminantes Químicos del Agua/toxicidadRESUMEN
The cortex exhibits an intricate vertical and horizontal architecture, the latter often featuring spatially clustered projection patterns, so-called patches. Many network studies of cortical dynamics ignore such spatial structures and assume purely random wiring. Here, we focus on non-random network structures provided by long-range horizontal (patchy) connections that remain inside the gray matter. We investigate how the spatial arrangement of patchy projections influences global network topology and predict its impact on the activity dynamics of the network. Since neuroanatomical data on horizontal projections is rather sparse, we suggest and compare four candidate scenarios of how patchy connections may be established. To identify a set of characteristic network properties that enables us to pin down the differences between the resulting network models, we employ the framework of stochastic graph theory. We find that patchy projections provide an exceptionally efficient way of wiring, as the resulting networks tend to exhibit small-world properties with significantly reduced wiring costs. Furthermore, the eigenvalue spectra, as well as the structure of common in- and output of the networks suggest that different spatial connectivity patterns support distinct types of activity propagation.
Asunto(s)
Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Redes Neurales de la Computación , Animales , Modelos Neurológicos , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Células Piramidales/anatomía & histología , Células Piramidales/fisiología , Procesos EstocásticosRESUMEN
Degeneration of axotomized GABAergic septohippocampal neurones has been shown to be enhanced in ciliary neurotrophic factor (CNTF)-deficient mice following fimbria-fornix transection (FFT), indicating a neuroprotective function of endogenous CNTF. Paradoxically, however, the cholinergic population of septohippocampal neurones was more resistant to axotomy in these mutants. As leukaemia inhibitory factor (LIF) has been identified as a potential neuroprotective factor for the cholinergic medial septum (MS) neurones, FFT-induced responses were compared in CNTF(-/-), LIF(-/-) and CNTF/LIF double knockout mice. In CNTF(-/-) mice, FFT-induced cholinergic degeneration was confirmed to be attenuated as compared with wildtype mice. The expression of both LIF and LIF receptor beta was increased in the MS providing a possible explanation for the enhanced neuronal resistance to FFT in these animals. However, ablation of the LIF gene also produced paradoxical effects; following FFT in LIF(-/-) mice no loss of GABAergic or cholinergic MS neurones was detectable during the first postlesional week, suggesting that other efficient neuroprotective mechanisms are activated in these animals. In fact, enhanced activation of astrocytes, a source of neurotrophic proteins, was indicated by increased up-regulation of glial fibrillary acidic protein and vimentin expression. In addition, mRNA levels for neurotrophin signalling components (e.g. nerve growth factor, p75(NTR)) were differentially regulated. The positive effect on axotomized cholinergic neurones seen in CNTF(-/-) and LIF(-/-) mice as well as the increased up-regulation of astrogliose markers was abolished in CNTF/LIF double knockout animals. Our results indicate that endogenous CNTF and LIF are involved in the regulation of neuronal survival following central nervous system lesion and are integrated into a network of neurotrophic signals that mutually influence their expression and function.
Asunto(s)
Factor Neurotrófico Ciliar/deficiencia , Factor Neurotrófico Ciliar/genética , Fórnix/fisiología , Factor Inhibidor de Leucemia/deficiencia , Factor Inhibidor de Leucemia/genética , Factores de Crecimiento Nervioso/metabolismo , Neuronas/fisiología , Tabique del Cerebro/citología , Tabique del Cerebro/metabolismo , Animales , Axotomía , Recuento de Células , Citocinas/biosíntesis , Femenino , Hipocampo/citología , Hipocampo/metabolismo , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Degeneración Nerviosa/patología , Sistema Nervioso Parasimpático/citología , Sistema Nervioso Parasimpático/fisiología , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
Glucocorticoids have been shown to influence trophic processes in the nervous system. In particular, they seem to be important for the development of cholinergic neurons in various brain regions. Here, we applied a genetic approach to investigate the role of the glucocorticoid receptor (GR) on the maturation and maintenance of cholinergic medial septal neurons between P15 and one year of age by using a mouse model carrying a CNS-specific conditional inactivation of the GR gene (GRNesCre). The number of choline acetyltransferase and p75NTR immuno-positive neurons in the medial septum (MS) was analyzed by stereology in controls versus mutants. In addition, cholinergic fiber density, acetylcholine release and cholinergic key enzyme activity of these neurons were determined in the hippocampus. We found that in GRNesCre animals the number of medial septal cholinergic neurons was significantly reduced during development. In addition, cholinergic cell number further decreased with aging in these mutants. The functional GR gene is therefore required for the proper maturation and maintenance of medial septal cholinergic neurons. However, the loss of cholinergic neurons in the medial septum is not accompanied by a loss of functional cholinergic parameters of these neurons in their target region, the hippocampus. This pinpoints to plasticity of the septo-hippocampal system, that seems to compensate for the septal cell loss by sprouting of the remaining neurons.