Activity-dependent regulation of dendritic growth and patterning

Dendritic morphology is tightly regulated during development and in the adult brain, reflecting its relevance to neuronal function. Both activity-dependent and activity-independent mechanisms participate in the growth and branching of dendrites. In many parts of the nervous system, dendritic arborizations are oriented in specific ways to receive their synaptic inputs. The fact that neurons of the same type bear striking similarities in their morphology, and that this is repeated from animal to animal, indicates that there is a genetic component to the regulation of dendritic morphology. The growth and patterning of dendrites can also be influenced by environmental signals, such as retrograde feedback from their targets and interactions with neighbouring cells of the same kind. Several molecules that mediate these effects have been identified. They include semaphorin 3A, Slit1, Notch and brain-derived neurotrophic factor. In many different species and brain structures, there is a close correlation between the arrival of afferents and dendritic maturation. This effect of afferent fibres occurs at two levels — they influence dendritic growth and regulate dendritic patterning. Similarly, the effects of afferent fibres depend on two factors — the arrival of the afferent axon and its synaptic output. Most studies have focused on the role of synaptic activity on dendritic development. The signalling pathways that are activated in response to synaptic activity to affect dendritic development are not fully understood, but calcium seems to be a crucial messenger. The effects of calcium can be global (for example, stimulating transcription through the activation of calcium/calmodulin-dependent protein kinase IV and cAMP-response-element-binding protein) or local (for example, acting on the cytoskeleton to stabilize growing dendrites). However, our understanding of the role of calcium on dendritic development remains rudimentary, and the signalling pathways that are involved in its effects remain to be precisely identified.