Target-specific regulation of synaptic amplitudes in the neocortex

In layers 2/ 3 in the rat visual cortex, glutamatergic synapses, between pyramidal neurons and GABAergic interneurons, show target-specific depression or facilitation. To study the mechanisms regulating these short- term synaptic modifications, we recorded from synaptically connected pyramidal neurons ( presynaptic) and multipolar or bitufted interneurons ( postsynaptic). Evoked AMPA receptor ( AMPAR)- or NMDA receptor ( NMDAR)- mediated EPSCs were pharmacologically isolated at these pyramidal- to- interneuron synapses while altering release probability ( P-r) by changing the extracellular Ca2+ concentration ([ Ca2+] (o)). At the pyramidal- to- multipolar synapse, which shows paired- pulse depression, elevation of [ Ca2+] (o) from physiological concentrations ( 2 mM) to 3 mM increased the amplitude of the initial AMPAR- mediated EPSC and enhanced paired- pulse depression. In contrast, the initial NMDAR- mediated EPSC did not change in amplitude with raised P-r nor was paired- pulse depression altered. This lack of an increase of NMDAR- mediated currents is not a result of Ca2+- dependent effects on the NMDAR. Rather, at the pyramidal- to- multipolar synapse, raised P-r increases the transient glutamate concentration at individual release sites, possibly reflecting multivesicular release. In contrast, at the pyramidal- to-bitufted synapse, which shows facilitation, AMPAR- and NMDAR- meditated EPSCs showed parallel increases in response to raised P-r. Thus, our results reveal differential recruitment of AMPA and NMDARs at depressing and facilitating synapses in layers 2/ 3 of the cortex and suggest that the mechanisms regulating dynamic aspects of synaptic transmission are target specific.