Figure 1. Proposed model for the levels of neuronal plasticity in antidepressant activity.

Neuronal plasticity acts at different structural levels and bidirectionally to influence variability and selection within neuronal networks. Increased formation of structures at any of these levels by, for example, environmental enrichment (EE) or chronic antidepressant treatment, generates variability and promotes competition between similar structures for stabilization, thereby enhancing adaptability, even if the total number of structures is not increased due to the simultaneous increase in structural elimination. 1. Neurogenesis and selective apoptosis. Increased precursor proliferation in the dentate gyrus, induced by antidepressants and EE, leads to the increased survival of newborn neurons that successfully mediate activity within the hippocampal circuitry. Neurons that fail to functionally integrate into the hippocampal circuitry are eliminated through apoptosis. 2. Arborization and pruning of axonal and dendritic branches. The increased dynamics of nascent branches promotes the stabilization of branches containing synapses that successfully represent environmental conditions, whereas arbors without active synapses remain short-lived and are pruned. 3. Synaptogenesis and synaptic elimination. Immature “trial synapses” between two neurons are initiated by filopodial extension from pre- or postsynaptic sites. Synapses that are successfully activated during the trial period are preferentially selected for stabilization, whereas contacts that fail to mediate activity collapse and are eliminated. 4. Plastic regulation of synaptic strength. Information transfer through active synapses is potentiated through the process of long-term potentiation (LTP), whereas inactive or inappropriately active synapses are suppressed through long-term depression (LTD). 5. Environmental activity regulates the transcription and translation of effector genes involved in neuronal plasticity through transcriptional control and epigenetic mechanisms, such as remodeling of chromatin structure from a closed to an open state.