Brain-derived neurotrophic factor requirement for activity-dependent maturation of glutamatergic synapse in...

The maturation of cortical circuitry critically depends on experience. Recently, a model of silent synapse has been proposed as a mechanism of activity-mediated transition of immature synapse to mature synapse. It is not clear, however, how activity could regulate this transition. Here, we show the evidence that endogenous brain-derived neurotrophic factor (BDNF) is required for the maturation of glutamatergic synapse in developing mouse somatosensory cortex. Field potential recordings of thalamocortical glutamatergic synaptic activity with brain slices from the BDNF mutant mice showed that AMPA receptor responses are low, but NMDA receptor responses remain high in layer 4, thus, the relative contribution of AMPA receptor response is significantly lower compared to the age-matched wild-type mouse. Furthermore, optical images of development of thalamocortical connectivity with a voltage-sensitive dye showed that NMDA receptor-dominant synapse is established first in layer 4 and layer 5/6 then AMPA receptor response appears later in concomitant with reduction of NMDA receptor response in layer 4 and that the maturation of the silent synapse is impaired in the BDNF mutant mice. In layer 5/6, NMDA receptor response was suppressed without upregulation of AMPA receptor response. This process also required BDNF function. Interestingly, whisker-trimming of the wild-type mouse from just after birth showed quite similar results with the homozygous mutant of their whiskers left intact. Therefore, we would propose that BDNF is a critical mediator for the maturation of glutamatergic synapse in developing mouse somatosensory cortex.