Section: New Results

Endocannabinoid dynamics gate spike timing dependent depression and potentiation

Participants: I. Prokin and H. Berry, in collaboration with L. Venance lab, CIRB, Collège de France, Paris.

Learning and memory depend on processes that alter the connections – or synapses – between neurons in the brain. For example, molecules called endocannabinoids can alter synapses to decrease the influence that one neuron has on another neuron’s activity. This “synaptic depression” is an important mechanism through which the brain can adapt to an experience. However, recent research also suggests that endocannabinoids might also increase the influence one neuron has on another neuron’s activity by strengthening the synaptic connection between neurons. This opposite process is known as synaptic potentiation, and is also important for learning from experience. But how do endocannabinoids manage to produce opposing effects? Using a combination of electrophysiological recording experiments from our experimental collaborator lab and mathematical modeling, we have deciphered the molecular mechanisms that govern the action of endocannabinoids at key synapses in rat brain slices. This revealed that both the levels and timing of endocannabinoid release control changes in the strength of the synaptic connections. Electrical stimulations that produced moderate amounts of endocannabinoids over a prolonged period led to synaptic depression. However, stimulation that produced short but large endocannabinoid peaks caused synaptic potentiation. The enzymes that control endocannabinoid levels thus play a crucial role in determining whether a given stimulation leads to the strengthening or weakening of a synaptic connection. In the type of synapses studied, changes to synaptic strength also depend on another chemical called dopamine. Abnormal dopamine production is implicated in a number of disorders, including Parkinson’s disease and addiction. These results have been published in eLife [16].