RESUMEN
For the past seven decades, the Hodgkin-Huxley (HH) formalism has been an invaluable tool in the arsenal of neuroscientists, allowing for robust and reproducible modelling of ionic conductances and the electrophysiological phenomena they underlie. Despite its apparent age, its role as a cornerstone of computational neuroscience has not waned. The discovery of dendritic regenerative events mediated by ionic and synaptic conductances has solidified the importance of HH-based models further, yielding new predictions concerning dendritic integration, synaptic plasticity and neuronal computation. These predictions are often validated through in vivo and in vitro experiments, advancing our understanding of the neuron as a biological system and emphasizing the importance of HH-based detailed computational models as an instrument of dendritic research. In this article, we discuss recent studies in which the HH formalism is used to shed new light on dendritic function and its role in neuronal phenomena.
Asunto(s)
Modelos Neurológicos , Neuronas , Potenciales de Acción/fisiología , Neuronas/fisiología , Fenómenos Electrofisiológicos , Plasticidad NeuronalRESUMEN
Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca2+ release from lysosomes in the dendrites. This Ca2+ release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca2+ signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling.
Asunto(s)
Calcio/metabolismo , Catepsina B/metabolismo , Espinas Dendríticas/metabolismo , Exocitosis/fisiología , Lisosomas/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Plasticidad Neuronal/fisiología , Células Piramidales/metabolismo , Animales , Dendritas/metabolismo , Espinas Dendríticas/fisiología , Hipocampo/citología , Masculino , Técnicas de Placa-Clamp , Células Piramidales/citología , Células Piramidales/fisiología , Ratas , Ratas Wistar , Transducción de SeñalRESUMEN
Brain derived neurotrophic factor (BDNF) is crucial for the formation of appropriate synaptic connections during development and for learning and memory in adults. Secretion of this neurotrophin is under activity-dependent control. Understanding which patterns of physiological activity regulate BDNF secretion is therefore an important step in the comprehension of its role. We have recently shown that back propagation of action potentials (bAPs) is the principal triggering mechanism of dendritic BDNF secretion occurring during ongoing neuronal activity in neuronal cultures. In the present addendum we discuss possible implications of bAPs-induced BDNF secretion on the construction and reorganization of neuronal networks.