Plasticity of Inhibiton

Despite the significant advancement made in revealing the mechanisms underlying learning-relevant long-term modifications in synaptic inhibition, several key questions remain to be answered: How is synaptic inhibition modified by learning to allow the maintenance of the memory engram while persevering the network stability? Are long-term modifications in the inhibition strength spread out evenly between all neurons in the network, or are they expressed particularly in neurons that are essential for the memory engram? How is the balance between synaptic excitation and inhibition maintained? Are long-term changes in synaptic transmission similar after different forms of learning, or are they specific to the complexity of the learned task, the significance of the reward and to the brain area in which they occur? Are they related to changes in intrinsic neuronal excitability? 

 

We study learning-induced modifications in inhibitory synaptic transmission, examining its particular expression in neurons which are part of the memory engram. Such modifications are induced in a precisely ordered dynamic manner, enabling the engram first to be shaped and then to be maintained. Specifically, during the period of shaping the engram synaptic inhibition is reduced in neurons which are more active, allowing their excitatory synaptic inputs to be strengthened. Subsequently, the inhibitory synaptic inputs onto these neurons are enhanced dramatically to stabilize the engram and prevent uncontrolled network activation. We also examined the hypothesis that learning-induced modifications in synaptic inhibition in neurons which form the memory engram are controlled by whole cell post-synaptic mechanisms, rather than by synapse-specific mechanisms, as predicted by our previous computational work.

In particular, we are address three major questions:

1. What are the general principles governing learning-induced long-lasting modifications in synaptic inhibition, which are functional across learning paradigms and brain regions?

2. What are the molecular and physiological mechanisms underlying long-term changes in inhibition?

3. Is there a causal relation between changes in synaptic inhibition and long-term memory?  

 

We study the mechanisms underlying learning-induced long-lasting modification in synaptic inhibition by combining whole cell patch clamp recordings with advanced single-cell labeling using Arc-dVenus,  precise single cell stimulation of optogenetically evoked interneurons and in-vivo application of drugs that would affect specifically neurons which are part of the engram.