Normal hearing is required for the emergence of long-lasting inhibitory potentiation in cortex.
Long-term synaptic plasticity is a putative mechanism for learning in adults. However, there is little understanding of how synaptic plasticity mechanisms develop or whether their maturation depends on experience. Since inhibitory synapses are particularly malleable to sensory stimulation, long-lasting potentiation of inhibitory synapses was characterized in auditory thalamocortical slices. Intracortical high-frequency electrical stimulation led to a 67% increase in inhibitory synaptic currents. In the absence of stimulation, inhibitory potentiation was induced by a brief exposure to exogenous brain-derived neurotrophic factor (BDNF). BDNF exposure occluded any additional potentiation by high-frequency afferent stimulation, suggesting that BDNF signaling is sufficient to account for inhibitory potentiation. Moreover, inhibitory potentiation was reduced significantly by extracellular application of a BDNF scavenger or by intracellular blockade of BDNF receptor [tropomyosin-related kinase B (TrkB)] signaling. In contrast, glutamatergic or GABAergic antagonists did not prevent the induction of inhibitory potentiation. Since BDNF and TrkB expression are influenced strongly by activity, we predicted that inhibitory potentiation would be diminished by manipulations that decrease central auditory activity, such as hearing loss. Two forms of hearing loss were examined: conductive hearing loss in which the cochleae are not damaged or sensorineural hearing loss in which both cochleae are removed. Both forms of hearing loss were found to reduce significantly the magnitude of inhibitory potentiation. These data indicate that early experience is necessary for the normal development of BDNF-mediated long-lasting inhibitory potentiation, which may be associated with perceptual deficits at later ages.
Xu
Han
H
Center for Neural Science and Department of Biology, New York University, New York, New York 10003, USA.
Kotak
Vibhakar C
VC
Sanes
Dan H
DH
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D000831:Animals, Newborn; D001303:Auditory Cortex / Q000502:physiology*; D001307:Auditory Perception / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D005849:Gerbillinae; D006309:Hearing / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor