LTP MAINTENANCE · Molecular mechanism for long-term maintenance of synaptic plasticity changes
6РП — Действия „Мария Кюри“
- Период
- 2005-10-01 → 2007-09-30
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите.
Накратко на български
Протеинът CREB и ролята му при превръщането на краткосрочните спомени в дълготрайни се изследват чрез промяна на активността му в невроните на мишки. Резултатите помагат да се разбере как да се манипулира този механизъм внимателно, за да се подобри оцеляването на невроните при дегенеративни заболявания.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - LTP MAINTENANCE (Molecular mechanism for long-term maintenance of synaptic plasticity changes)
Our laboratory is interested in the role of CREB (cAMP-response element binding protein) dependent gene expression in processes of learning and memory acquisition. The activation of the transcription factor CREB is necessary for the conversion of short term in long lasting memories. The objective of this project was to study the effects of overexpression and inhibition of CREB in the electrophysiological properties of CA1 pyramidal neurons. In order to achieve those goals we used transgenic mice that overexpress a constitutive active form of CREB (VP16-CREB) or a competitive inhibitor of CREB (A-CREB) under the tTA system that allowed us to control the expression temporally. I recorded intracellular activity from CA1 piramidal neurons in in vitro slices that contained the hippocampus using patch-clamp pipettes. The main outcome was that VP16-CREB expression increased the excitability of CA1 neurons reducing the slow after hyperpolarization (AHP). This finding may explain the reduced threshold for long-term potentiation, a possible cellular substrate for learning and memory, which has been associated to this activity. We also observed that sustained activation of CREB produced epileptic attacks in these mice. We showed that the increase in excitability produced by the expression of VP16-CREB in CA1 neurons, modified the activity of the whole hippocampal network. Those alterations caused epileptic seizures and triggered degeneration of those neurons by excite-toxicity, as we confirmed with histological techniques. These results with the on-going analysis of A-CREB mice are important because some therapies for neurodegenerative diseases have considered targeting the CREB pathway to promote neuronal survival. We showed that manipulation of CREB pathway should be very precise in order to avoid non-desired effects. In conclusion, these findings have important implications for both the understanding of the molecular and cellular bases of learning and memory and the consideration of therapies targeted to the CREB pathway.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Dynamic changes in synaptic strength are now thought to be the cellular mechanisms responsible for information storage in the nervous system. The formation of long-term memory and the expression of long term synaptic plasticity require the activation of gene transcription and protein synthesis de novo. In this context the CREB family of transcription factors appears to be one of the core components in the molecular switch that converts short- to long-term memory.The aim of this project is to study the role of the CREB family of transcription factors in the acquisition and consolidation of memories. We will use different lines of transgenic mice related with the CREB transcription factors such as VP16-CREB (a constitutively active CREB variant), A-CREB (a dominant negative CREB mutant), VP16-SRF (a constitutively active SRF variant) and CBP (CREB co-activator) to study memory formation and consolidation. As a member of a multidisciplinary group I will carry out electrophysiological studies to characterized synaptic plasticity phenomena in the hippocampus and amygdala, two structures that are related with spatial and fear conditioned memories respectively.These data together with behavioural experiments will allow us to understand the molecular processes of learning and memory. The results of this project may help to find treatments for the increasing number of neuro-degenerative diseases in the European countries as a consequence of the ageing population.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSIDAD MIGUEL HERNANDEZ DE ELCHE · ELCHEКоординаторИспания
Връзки
Данни: CORDIS, © Европейски съюз