The impact of neuronal activity on functional re-wiring of hippocampal CA1 excitatory neurons.
Final Report Abstract
The cellular mechanisms enabling neurons to store information are still not well understood. It is commonly thought that learning activates ensembles of neurons, inducing persistent physical/chemical changes in these neurons. These changes enable specific reactivation of these neuronal ensembles by relevant cues and hence the retrieval of a specific memory. These persistent changes include both molecular and structural modifications at the level of single neurons and neuronal circuits. The advent of two-photon microscopy has enabled the performance of seminal studies that have recently shed light on the structural changes linked to behavior in several brain areas in live mice. Not only has a surprisingly high level of structural dynamics of dendritic spines and inhibitory synapses been demonstrated, but also a direct correlation between such dynamics and learning has emerged. However, the mechanisms by which structural changes in connectivity support the formation and recall of memories are poorly understood in the hippocampus – a brain area key for memory and navigation. To tackle this fundamental question, we used a combination of deep-brain optical imaging and advanced viral labeling to: (i) describe (for the first time) the long-term dynamics of inhibitory synapses impinging on pyramidal neurons in the dorsal CA1 region of the hippocampus of live mice and (ii) investigate the link between structural plasticity of excitatory and inhibitory synapses and the ability of mice to learn and recall hippocampus-dependent memories. We found that: (i) the dynamics of inhibitory synapses are compartmentalized – that is, dendrites, somata, and axon initial segments of pyramidal neurons all have specific characteristics; (ii) the dynamics of dendritic inhibitory synapses are tendentially slower than the dynamics of dendritic spines; (iii) learning of a hippocampus-dependent memory task strongly affects inhibitory synapses located in the dendrites and axon initial segment, but much less so inhibitory synapses located on the soma; and (iv) recall has the strongest effect on dendritic spines.
