Continual learning and memory for sounds in rat

Descripción del proyecto

Estabilidad de la memoria y plasticidad neuronal

El cerebro tiene la capacidad única de adaptarse modificando las sinapsis y reorganizando los circuitos neuronales, un proceso denominado «plasticidad neuronal». Esta flexibilidad permite el aprendizaje y la formación de nuevos recuerdos. No obstante, surge la cuestión de cómo los recuerdos antiguos se mantienen estables pese a los cambios continuos en la actividad neuronal y la renovación sináptica. Para abordar esta cuestión, el proyecto MEMORAT, financiado por el Consejo Europeo de Investigación, tiene por objeto estudiar el aprendizaje auditivo continuo. Los investigadores utilizarán ratas como sistema modelo, que serán entrenadas para reconocer hasta cien sonidos a lo largo de varios meses. En este sentido, emplearán técnicas avanzadas de registro neuronal para observar la adquisición y consolidación de la memoria. En conjunto, se prevé que la investigación esclarezca cómo el cerebro equilibra la estabilidad y la flexibilidad de la memoria.

Objetivo

How much can we remember and for how long? Decades of key advances in our understanding of synaptic plasticity resulted in a puzzle. On the one hand, memories can be highly stable and organisms are capable of adding new memories without destroying old ones. On the other hand, data and models support neither stability nor lifelong (‘continual’) learning. Many experiments suggest that responses of neuronal populations slowly but inexorably drift (“representational drift”), while synapses spontaneously turnover. At the same time, models predict that memory traces of new experiences tend to interfere destructively with old traces. Here, I will study auditory continual learning in the behaving rat. I will develop a novel behavioral paradigm that will train rats to recognize two new sounds every few days, memorizing up to 100 sounds over 3-4 months of continuous training, and check the stability of memory during that time. My lab will apply state-of-the-art recording techniques in order to document the neural activity during memory acquisition and between training sessions while the rats sleep and consolidate newly acquired memories. I will repeat these studies in a rat model for Alzheimer’s disease, which expresses early memory deficits. These results will be compared with predictions of models for memory in the auditory cortex. At one end, I will test the predictions of a model, based on recently published results, that posits the existence of a few neurons that carry the memory of each learned sound by intrinsic bursting. At the opposite end, I will test predictions of models in which memory resides in the coordinated activity of large, distributed ensembles of neurons. Overall, this project will address the deep puzzles of memory when memory load is high, a regime that has not been studied in animal models.