Functional Relevance of Endocannabinoid-Dependent Synaptic Plasticity in the Central Nervous System

Abstract

The endocannabinoid (eCB) signaling system plays a key role in short-term and long-term synaptic plasticity in brain regions involved in various neural functions ranging from action selection to appetite control. This review will explore the role of eCBs in shaping neural circuit function to regulate behaviors. In particular, we will discuss the behavioral consequences of eCB mediated long-term synaptic plasticity in different brain regions. This review brings together evidence from in vitro and ex vivo studies and points out the need for more in vivo studies.

Keywords: 2-arachidonoylglycerol; Arachidonoylethanolamine; cannabinoid receptors; depolarization-induced suppression of excitation; depolarization-induced suppression of inhibition; long-term depression; long-term potentiation.

Figure 1.

Proposed eCB mediated synaptic plasticity functional map in rodent brain. Schematic illustration of brain structures, specialized functions, and microcircuitry involved in eCB-LTD. eCBs have the potential to modulate goal-directed, habitual, and reward-driven behaviors in the striatum by DA regulation of eCB mediated LTD at excitatory synapses and eCB mediated LLD and LTD at inhibitory synapses. eCBs work in a layer specific manner at excitatory and inhibitory synapses in the somatosensory and visual cortices to process incoming sensory information. Hippocampal eCB synaptic depression has been reported at CCK-basket cell interneuron-pyramidal cell synapses and at excitatory terminals of Schaffer collaterals arising from CA3. There, eCB-mediated plasticity is postulated to play an important role in learning and memory formation, and can contribute to seizures and epileptic disorders. In the cerebellar cortex, eCBs mediate synaptic depression of Purkinje cell inputs to control motor learning and conditioning of reflexes. eCB mediated changes in synaptic transmission in the hippocampus and amygdala modulate fear-associated memory formation. DA, dopamine; FC, frontal cotex; OFC, obritofrontal cortex, MSN, medium spiny neuron; CIN, cholinergic interneuron; FSI, fast-spiking interneurons; glut, glutamatergic; PC, purkinje cell; PF, parallel fibers; CF, climbing fibers; GC, granule cell; CCK, cholecytokinin; SC, Schaffer collaterals; PV, parvalbumin positive neurons.