Impact of subthreshold membrane potential on synaptic responses at dendritic spines of layer 5 pyramidal neurons in the prefrontal cortex

Glutamatergic inputs onto cortical pyramidal neurons are received and initially processed at dendritic spines. AMPA and NMDA receptors generate both synaptic potentials and calcium (Ca) signals in the spine head. These responses can in turn activate a variety of Ca, sodium (Na), and potassium (K) channels at spines. In principle, the roles of these receptors and channels can be strongly regulated by the subthreshold membrane potential. However, the impact of different receptors and channels has usually been studied at the level of dendrites. Much less is known about their influence at spines, where synaptic transmission and plasticity primarily occur. Here we examine single-spine responses in the basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. Using two-photon microscopy and two-photon uncaging, we first show that synaptic potentials and Ca signals differ at resting and near-threshold potentials. We then determine how subthreshold depolarizations alter the contributions of AMPA and NMDA receptors to synaptic responses. We show that voltage-sensitive Ca channels enhance synaptic Ca signals but fail to engage small-conductance Ca-activated K (SK) channels, which require greater numbers of inputs. Finally, we establish how the subthreshold membrane potential controls the ability of voltage-sensitive Na channels and K channels to influence synaptic responses. Our findings reveal how subthreshold depolarizations promote electrical and biochemical signaling at dendritic spines by regulating the contributions of multiple glutamate receptors and ion channels.