Neurotrophin-4/5 alters responses and blocks the effect of monocular deprivation in cat visual cortex during the critical period.
The mechanisms underlying changes in neural responses and connections in the visual cortex may be studied by occluding one eye during a critical period in early postnatal life. Under these conditions, neurons in the visual cortex rapidly lose their responses to the deprived eye and ultimately lose many of their inputs from that eye. Cats at the peak of the critical period received infusions of exogenous neurotrophin NT-4/5 into primary visual cortex beginning before a short period of monocular deprivation. Within areas affected by NT-4/5, cortical cells remained responsive to the deprived eye, and maps of ocular dominance were no longer evident using intrinsic-signal optical imaging. Cortical cells also became broadly tuned for stimulus orientation and less responsive to visual stimulation through either eye. These effects required at least 48 hr exposure to the neurotrophin and were specific for trkB, because they were not seen with the trkA or trkC ligands NGF or NT-3. Even after neurons had already lost their responses to the deprived eye, subsequent NT-4/5 infusion could restore them. The NT-4/5 effects were not seen after the critical period. Together, these results suggest that trkB activation during the critical period may promote promiscuous connections independent of correlated activity.
Gillespie
D C
DC
Keck Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, California 94143-0444, USA.
Crair
M C
MC
Stryker
M P
MP
D000375:Aging / Q000502:physiology; D000818:Animals; D001931:Brain Mapping; D002415:Cats; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D007263:Infusions, Parenteral; D008024:Ligands; D008845:Microinjections; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009949:Orientation / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism; D012683:Sensory Deprivation / Q000502:physiology*; D014793:Visual Cortex / Q000098:blood supply / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D008024:Ligands; D009414:Nerve Growth Factors; C071951:neurotrophin 5; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; C073922:neurotrophin 4