title: Layer-specific thalamocortical innervation in organotypic cultures is prevented by substances that alter neural activity.
abstract: Cortical layer IV is the major target of thalamocortical axons and many previous studies have shown that the development of this layer-specific innervation can be modelled in vitro by organotypic cocultures of thalamus and cortex. The mechanisms causing thalamic axons to terminate in layer IV are unknown. We used these in vitro models to test the possibility that neural activity plays a part in this termination process by adding substances that raise or lower levels of neural activity to the cocultures. We found that addition of tetrodotoxin or 2-amino-5-phosphonovalerate, to block activity, or potassium, to raise it, all interfered with termination in layer IV. These findings suggest that termination in layer IV requires neural activity at an appropriate level in the thalamocortical system. They also add support to recent findings that show that the importance of neural activity in development may extend to an earlier period than thought previously, to include the correct targeting of axons as well as the later refinement of connections.
authors.affiliation: Genes and Development Group, Biomedical Sciences Section, Hugh Robson Building, George Square, Edinburgh EH8 9XD, Scotland, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Anderson
authors.forename: David J
authors.initials: DJ
authors.lastname: Price
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D018920:Coculture Techniques; D005333:Fetus; D005456:Fluorescent Dyes; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D011188:Potassium / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D013788:Thalamus / Q000166:cytology / Q000196:embryology* / Q000254:growth & development
chemical_list: D005456:Fluorescent Dyes; D013779:Tetrodotoxin; D015763:2-Amino-5-phosphonovalerate; D011188:Potassium