Mechanisms Underlying Learning-Associated Neural Plasticity

Post by Lina Teichmann

What's the science?

Altering strategies or flexibly adapting to changes in any given environment is critical for survival. In the context of spatial navigation, learning leads to increased connectivity between the ventral hippocampus (vHPC) and the medial prefrontal cortex (mPFC). While this vHPC-mPFC connectivity enhances initial performance in the learned task, it makes it harder to flexibly adapt to new circumstances. This week in Nature, Park and colleagues examined neural mechanisms underlying adaptive learning. They tested mice on spatial learning tasks and investigated how novelty impacts vHPC - mPFC circuitry to allow for cognitive flexibility.

How did they do it?

Groups of mice freely explored a T-shaped maze in which they were rewarded for visits to either arm of the maze. Over the course of three days, mice simply chose one particular arm side to get the reward. Next, in a new ‘flexible choice’ task, the mice had to overcome their bias of choosing one arm over the other to receive a reward. To examine the effect of novelty on cognitive flexibility, a subgroup of mice was exposed to a new spatial environment or a new mouse before starting the flexible choice task. The mice which were exposed to novel environments learned to overcome their spatial bias and adapt to the new task more rapidly than mice who were not exposed to novelty before completing the task. This suggests that novelty had a positive effect on flexible learning. Recording neuronal activity from electrodes implanted into vHPC, dorsal HPC, and mPFC, the authors examined the neural firing reflecting learning-associated plasticity. In addition, they used optogenetics to stimulate vHPC terminals in the mPFC to directly examine the effect of novelty on vHPC-to-mPFC synaptic transmission. To test whether dopamine D1 receptors modulated learning through novelty, they also infused dopamine receptor agonists and antagonists.

What did they find?

Mice exposed to novel environments showed stronger theta rhythms, which are associated with learning. Theta rhythms reorganized the firing pattern of vHPC neurons in the novelty-exposed mice group, leading to a decrease in connectivity between vHPC and mPFC. This decreased connectivity means that adherence to the old task strategy is weakened, which more readily allows for adaptation to new task demands. In other words, to improve spatial learning in a new task, the vHPC – mPFC connectivity must first be reset, which is facilitated by novelty. Learning the new task strengthens the vHPC – mPFC connectivity once again and the mPFC encodes information associated with the old and the new task which allows for cognitive flexibility.

What's the impact?

This study demonstrates that novelty triggers a reset of vHPC - mPFC circuitry, enhancing new learning in mice. The findings elucidate the neural mechanisms involved in flexible adaptation to changing environments and open future avenues for examining how novelty affects learning in humans.

Park et al. Reset of hippocampal-prefrontal circuitry facilitates learning. Nature (2021). Access the original scientific publication here.