5.2 Long-term Potentiation

We have seen that habituation and sensitization in the Apylsia  demonstrate that there are changes that occur at the level of the synapse with learning. We also see changes at the synaptic level with associative learning, where two unrelated stimuli are linked together, such as a particular sound with your phone signaling a call or text, or a face with your grandmother. Associative memory constitutes a very large proportion of our explicit memories.

Studies of the synaptic changes that occur with associate learning have found changes to occur at the post-synaptic neuron. The first documentation of this came from the studies Bliss and Lomo in 1973 (Nicoll, 2017). Using anesthetized rabbits, they demonstrated synapses in the hippocampus showed increased excitatory responses that lasted for hours and even days.  Bliss and Lomo named this long-lasting response long-term potentiation, commonly referred to as LTP.  Many studies have been done since their seminal work that have established that LTP within the hippocampus is the foundation for long-term memory.

Like habituation and sensitization, there are changes that occur with sensitivity to neurotransmitters. In the case of LTP, repeated high frequency stimulation to the presynaptic neuron, results in increased amplitude of the excitatory postsynaptic potentials (EPSPs). In excitatory neurons in the hippocampus, this occurs when the neurotransmitter glutamate is released in the synapse.  A strong signal releases a large amount of glutamate in the synapse which activates two types of receptors on the post-synaptic membrane. This results in depolarization at the post-synaptic neuron. Calcium and sodium play a role in this process. In a late phase of LTP, new proteins are formed.

There is a parallel process for inhibition, called long-term depression (LTD). This results in cells being less responsive and involves GABA, the major inhibitory neurotransmitter.

While most studies on synaptic changes have focused on activity at the post-synaptic sites, there are ongoing studies to investigate changes occurring at the presynaptic neurons (Kolb et al., 2016).