Unlocking Memory: How the Lateral Entorhinal Cortex CA3 Circuit Stabilises Learning

Have you ever returned to a childhood holiday spot and instantly recognised the street layout, even though new shops had replaced the old ones? Your brain must balance the flexibility to update new details with the stability to keep the core map intact. A recent study investigates the biological machinery responsible for this, focusing specifically on the lateral entorhinal cortex CA3 circuit.

The researchers measured neuronal activity in mice to understand how long-range signals influence local brain areas. They discovered a sophisticated push-pull system involving two distinct chemical messengers: glutamate and GABA.

The Role of the Lateral Entorhinal Cortex CA3 Circuit

If the lateral entorhinal cortex (LEC) sends a glutamatergic signal, it excites the memory centre (CA3). However, the team observed that this signal also triggers a strong safety mechanism. It activates local inhibitory neurons that clamp down on activity. It effectively stops the main neurons from spiking. It is like revving a car engine while standing firmly on the brake.

But to learn, the brain must let the car move. This is where the second signal enters. The study shows that the LEC also projects GABA-ergic signals. If these signals arrive, they suppress the local inhibition. By cutting the brake cables, they allow the CA3 neurons to fire.

The data indicates that this synergy—driving excitation while selectively releasing the brakes—is required to stabilise 'place cells'. These are neurons that fire in specific physical locations. The authors suggest that without this precise control from the lateral entorhinal cortex CA3 circuit, our mental maps might drift or fade when contexts change.