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In the last decade, in vivo studies of neuronal morphological dynamics in superficial layers of the cerebral cortex have shown that while adult circuits are predominantly stable, both pre- and postsynaptic terminals in the adult cortex maintain a ‘plastic’ capacity for change on a day-to-day basis. This baseline plasticity can be further enhanced by experiential stimuli. As these studies are extended to more cortical areas and different experimental paradigms, and are analyzed with more attention to cell type and location, the rules governing synaptic structural plasticity in the adult are becoming evident.

During development, neuronal activity sculpts maturing brain circuits. Synapses and arbors are dynamically refined through an activity-dependent process of synaptic weakening and subsequent pruning, as well as synaptic strengthening and stabilization. Intracellular signaling pathways mediate between neuronal activity and structural remodeling by integrating input activity and initiating transcription of activity-regulated genes. Activity-regulated gene products then utilize multiple mechanisms to modulate synaptic strength, number, and arbor morphology.

Modifications of neuronal circuits allow the brain to adapt and change with experience. This plasticity manifests during development and throughout life, and can be remarkably long lasting. Evidence has linked activity-regulated gene expression to the long-term structural and electrophysiological adaptations that take place during developmental critical periods, learning and memory, and alterations to sensory map representations in the adult. In all these cases, the cellular response to neuronal activity integrates multiple tightly coordinated mechanisms to precisely orchestrate long-lasting, functional and structural changes in brain circuits. Experience-dependent plasticity is triggered when neuronal excitation activates cellular signaling pathways from the synapse to the nucleus that initiate new programs of gene expression. The protein products of activity-regulated genes then work via a diverse array of cellular mechanisms to modify neuronal functional properties. Synaptic strengthening or weakening can reweight existing circuit connections, while structural changes including synapse addition and elimination create new connections. Posttranscriptional regulatory mechanisms, often also dependent on activity, further modulate activity-regulated gene transcript and protein function. Thus, activity-regulated genes implement varied forms of structural and functional plasticity to fine-tune brain circuit wiring., National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (F31 NS069510), RO1 EY011894