Cortical transmission is largely mediated by ionotropic neurotransmitter receptors that produce fast (<10 ms) synaptic conductances. Glutamate elicits fast excitation via the activation of cation permeable AMPA and NMDA receptor-mediated conductances, while GABA evokes fast inhibition via anion (Cl− and HCO3−) permeable GABAA receptor-mediated conductances. The possibility of varying the ratio between synaptic excitation and inhibition allows for the shifting of the membrane potential of a neuron towards any arbitrary value in-between the reversal potential of synaptic excitation (around 0 mV for AMPA and NMDA receptors) and synaptic inhibition (typically around −70 to −80 mV for GABAA receptors). Thus, by changing the ratio between synaptic excitation and inhibition, neuronal membranes can be rapidly brought to threshold for action-potential generation, just near threshold or far below threshold in a matter of a few milliseconds (Fig. 3A) (Higley and Contreras, 2006). Furthermore, even a specific ratio between excitation and inhibition can lead to different membrane potentials depending on the absolute magnitude of the two opposing conductances. In fact, since synaptic excitation and inhibition are not the only conductances of a neuron, their
