Trends in Neurosciences
Sperry and Hebb: oil and vinegar?
Section snippets
The purpose of experience-dependent refinement of synaptic connections
Sensory and motor experiences during a critical period of development sculpt the organization of afferent projections within the brain. Each animal has a different physiognomy, different gross anatomy and differences in sizes of different brain regions [8]. The ethological significance of activity-dependent refinement of sensory and motor projections is to allow individual projections to be molded according to individual gross anatomical differences, as shown in the elegant experiments in barn
The chemoaffinity hypothesis in the modern era
Sperry's chemoaffinity hypothesis stated that the specificity of mapping of presynaptic and postsynaptic partners is determined by molecular cues. Originally, Sperry proposed that different cells bear distinct cell surface proteins that serve as markers or tags [10]. Later, upon consideration that the genome was unlikely to encode as many proteins as would be required by this model, Sperry suggested that dual gradients of molecules in the afferent and target fields would allow topographic
Genetic specification of synaptic partners
It is widely accepted that learning is mediated by changes in circuit connectivity comparable to those that occur during development. If this is so, then molecular markers designating presynaptic and postsynaptic partners during development cannot establish rigid connectivity for the lifetime of the animal. So far, the most convincing evidence for a role for cadherins in synaptic connectivity comes from Drosophila [26]. However insects, like most other metazoans, do learn, and physical changes
Can Hebb help?
The limitations of the hypotheses suggesting that cell-surface adhesion molecules specify synaptic partner choice are readily addressed by including activity-dependent regulatory events in mechanistic models of brain development. Although the combined use of activity-independent and activity-dependent mechanisms to refine sensory projections is well established [33], it is worth restating in this post-genomic era. A key aspect in the idea of activity-dependent regulation of connectivity is that
Activity-dependent regulation of gene expression
With respect to spatiotemporal patterns of gene expression and protein synthesis, environmental signals, including those that affect neuronal activity, clearly regulate gene expression [37]. Protein synthesis and degradation are regulated locally by activity-dependent mechanisms in dendrites and, possibly, also in axons 19, 38. Although this topic has been recently reviewed [39], it is worth mentioning briefly because local activity-dependent regulation of protein synthesis could affect the
Activity-dependent changes in circuit properties
Examples of activity-dependent effects on circuit properties are numerous. Studies performed more than ten years ago in Drosophila demonstrated an intimate relationship between activity patterns and structural plasticity at the neuromuscular junction [44]. These initial studies have been supported by a substantial literature that demonstrates significant activity-induced changes in neuronal structure and function in Drosophila, as well as activity-dependent changes in gene expression, protein
Vinaigrette
Developmental biologists have long recognized that the formation of an organism is the result of a complex pas de deux between the environment and the genome. Such continuous and complex interactions also operate during brain development. Here, I have discussed the added value in synthesizing so-called ‘activity-independent’ and ‘activity-dependent’ mechanisms into more realistic models of brain development. In fact, these very terms have limited descriptive value in light of the high degree of
Acknowledgements
I thank Jeff Lichtman, Carla Shatz, Stephen J. Smith, Tim Tully and members of my laboratory for insightful discussions.
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