Endocannabinoid-mediated short-term synaptic plasticity: depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE)

Depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE) are two related forms of short-term synaptic plasticity of GABAergic and glutamatergic transmission, respectively. They are induced by calcium concentration increases in postsynaptic cells and are mediated by the release of a retrograde messenger, which reversibly inhibits afferent synapses via presynaptic mechanisms. We review here: The evidence accumulated during the 1990s that has led to the conclusion that DSI/DSE rely on retrograde signaling. The more recent research that has led to the identification of endocannabinoids as the retrograde messengers responsible for DSI/DSE. The possible mechanisms by which presynaptic type 1 cannabinoid receptors reduce synaptic efficacy during DSI/DSE. The possible modes of induction of DSI/DSE by physiological activity patterns, and the partially conflicting evaluations of the calcium concentration increases required for cannabinoid synthesis. Finally, the relation between DSI/DSE and other forms of long- and short-term synaptic inhibition, which were more recently associated with the production of endocannabinoids by postsynaptic cells. Keywords: DSI, DSE, endocannabinoids, CB1 receptors, short-term synaptic plasticity, GABAergic transmission, glutamatergic transmission, retrograde messengers The law of dynamic polarization: a rule with many exceptions The classical concept of interneuronal communication holds that information flows from the axon terminals of the presynaptic neuron to the dendrites of its postsynaptic partner. This idea was stated by Santiago Ramon y Cayal under the name of ‘law of dynamic polarization'. With hindsight, it is clear that the law of dynamic polarization cannot be considered as stringent as a physics law, and that it suffers many exceptions. Already, Cajal had recognized that, for example, many neurons throughout the animal kingdom lack axons; in such neurons, the law of dynamic polarization can clearly not hold. Nevertheless, this law has guided the thinking of neuroscientists up to the present time, so that exceptions from it have been slow to be recognized and accepted. Certain sets of neurons, including interneurons, are now recognized as being connected via dendro-dendritic or axo-axonal electrical synapses (review: Galarreta & Hestrin, 2001). In addition, it is well established that neurons (e.g. in the olfactory bulb, Shepherd & Greer, 2001, or for the thalamic GABAergic F-terminals, Sherman & Guillery, 2001) are able to release neurotransmitters from structures closely resembling ‘classical' axonal synaptic terminals, but which are classified as dendritic according to present identification criteria. Finally, many central neurons appear to be capable of releasing neurotransmitter-like substances from nonsynaptic areas of their somatodendritic compartment. These substances are able to modulate neurotransmitter release from afferent presynaptic terminals and include dopamine (Cheramy et al., 1981; Jaffe et al., 1998), dynorphin (Drake et al., 1994), glutamate and GABA (Zilberter et al., 1999; Zilberter, 2000), oxytocin and vasopressin (Kombian et al., 1997). Since they act in a direction which is opposite to that proposed by Cajal, they can be defined as ‘retrograde messengers' (for a thorough review of retrograde signaling in the nervous system, see, Alger, 2002). Endocannabinoids are an especially important class of retrograde messengers. Unlike the above compounds, which act primarily as ordinary neurotransmitters or neurohormones, and incidentally as retrograde messengers, so far endocannabinoids have been found to act primarily or exclusively as retrograde messengers in the mammalian brain. This special adaptation could be due to the fact that, following synthesis from membranous, lipidic precursors (Di Marzo et al., 1998; Piomelli et al., 2000), they are not stored in vesicles like the above transmitters, but rather released presumably by diffusing across membranes. Moreover, they have recently been discovered to play a prominent role both in short-term and in long-term synaptic plasticity, as well as to directly control the rate of firing of presynaptic cells. In this review, we focus on the retrograde, short-term inhibitory actions of cannabinoids on afferent GABAergic and glutamatergic transmission, which are respectively known as depolarization-induced suppression of inhibition, or DSI, and depolarization-induced suppression of excitation, or DSE.