UNLOCKING LEARNING

Where are our memories stored? How is information stored in the brain?Philosophers and scientists have been exploring these questions ever since the brain was discovered to control thought and reason. In 1973 Bliss and Lømo described a phenomenon known as long-term potentiation (LTP),where electrical stimulation of neurons during experiments results in an artificial increase, or potentiation, in synaptic strength. Although LTP has been extensively studied as a cellular model of memory formation, until now it has not been directly shown that learning in a living animal actually induces LTP. Jonathon Whitlock and colleagues from The Picower Institute for Learning and Memory at Massachusetts Institute of Technology demonstrate for the first time that a learning task in rats can induce LTP in a brain area called the hippocampus, which plays a role in memory formation.

Given a choice, rats will choose a dark environment over a well-lit one,unless they receive a nasty foot shock each time they enter the dark environment. This type of training is called inhibitory avoidance training and rats learn to avoid the dark environment after a single foot shock, staying in the well-lit one instead. Already knowing that an area of the hippocampus called CA1 is critical for inhibitory avoidance learning, the authors searched this brain area to see if this type of learning forms potentiated synapses,indicating LTP.

To investigate synapse strength, the team implanted several electrodes into the CA1 area of live animals, and stimulated the input neurons to that area. They measured the strength of the synaptic responses both before and after training. The authors found that inhibitory avoidance training caused potentiation at approximately 25% of the recording locations. This was not unexpected, because potentiating every synapse after learning a task is unnecessary to indicate LTP and probably a waste of energy for the network.

When no further LTP can be induced at a synapse, it is said to be saturated. Previous reports have shown that learning can result in saturation at certain synapses, indirectly indicating that learning induced LTP. Having found that the training potentiated about 25% of the recorded synapses, the authors then applied a stimulus to CA1 known to induce LTP across synapses,and measured the response to see if they could induce further LTP. They saw no further potentiation at recording locations already showing LTP from the first experiment, showing that the synapses were saturated and could not increase in strength any further. In contrast, stimulation did cause LTP at locations that did not show LTP before training.

The authors suggest that other researchers could not find LTP specifically induced by learning because synapses potentiated by learning are sparsely and widely distributed, making them difficult to detect in a vast sea of unmodified connections. Their data showing potentiation at only some of the recording locations supports the idea that associative memories are stored in many locations, and also means that these types of memories can be recalled when retrieval cues only partially match the original situation. Sparse distribution could also render the memory more robust in case some synapses fail to respond. If this were true, memory recall for inhibitory avoidance training would still be successful if LTP was disrupted at just a subset of the electrodes showing learning-induced LTP after training.