RESUMO
Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice as a learning task followed by 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase in the size of astrocytic glycogen granules, which are a source of lactate for neurons. The selective inhibition of glycogen metabolism in astrocytes impaired learning, affecting all the related synaptic changes. Intrahippocampal administration of l-lactate rescued the behavioral phenotype, along with spine density within 24 hours. Spine dynamics in hippocampal organotypic slices undergoing theta burst-induced long-term potentiation was similarly affected by inhibition of glycogen metabolism and rescued by l-lactate. These results suggest that learning primes astrocytic energy stores and signaling to sustain synaptic plasticity via l-lactate.
Assuntos
Astrócitos/ultraestrutura , Glicogênio , Ácido Láctico/administração & dosagem , Aprendizagem/fisiologia , Sinapses/metabolismo , Sinapses/ultraestrutura , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Glicogênio/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Aprendizagem/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Sinapses/efeitos dos fármacosRESUMO
The rapid involution that happens in some muscles of ungulate fetlock joints has never been investigated at an ultrastructural level. In this study, the proximal sesamoidean ligament (PSL) of sheep was chosen as a model to investigate, at the cellular level, the transition from muscle to connective structures that occurs during early development. In particular, we were interested in observing the presence of satellite cells and fibroblasts, detecting fluctuations in their numbers in the postnatal developing PSL, and evaluating putative apoptotic mechanisms. Interestingly, some features were shared by both PSL involution and muscle ageing; the most relevant being the significant and rapid decrease in the number of satellite cells together with a quick proliferation of fibroblasts in the muscle-connective transitional area (MCT-TA). Electron microscopy and immunohistochemical analyses revealed putative cellular mechanisms that led to a progressive involution of the muscle portion of the PSL during postnatal growth. Our findings showed a fast transition from muscle to connective tissue due to the depletion of satellite cells, apoptosis of some muscle fibres, and simultaneous proliferation of fibroblasts originating from mesenchymal progenitors or from differentiation of satellite cells typically located at the border between muscle and connective tissue of the PSL.