NMDA receptor-mediated components of miniature excitatory synaptic currents in developing rat neocortex

Area of Science:

• Neuroscience
• Developmental Biology
• Electrophysiology

Background:

• The early development of excitatory neurotransmission in the neocortex is crucial for circuit formation.
• Understanding the developmental trajectory of synaptic currents provides insights into neuronal maturation.

Purpose of the Study:

• To investigate the developmental changes in excitatory postsynaptic currents (EPSCs) in rat neocortical pyramidal neurons during the first two postnatal weeks.
• To characterize the properties of miniature EPSCs (mEPSCs) and evoked EPSCs and their dependence on N-methyl-D-aspartate (NMDA) receptor activity and extracellular magnesium.

Main Methods:

• Whole-cell patch-clamp recordings were performed on layer II-III pyramidal neurons in in vitro slices of rat frontal neocortex from postnatal days (PN) 3-14.
• Spontaneous and evoked EPSCs, as well as miniature EPSCs (mEPSCs), were analyzed for kinetic properties (rise time, decay time constant), amplitude, and frequency.
• The roles of NMDA receptors and extracellular magnesium were assessed using specific antagonists and ion manipulations.

Main Results:

• Key properties of mEPSCs, including rise time, amplitude, decay time constant, and frequency, did not significantly change between PN 3-5 and PN 9-14.
• mEPSC kinetics were voltage-dependent, with slower kinetics at depolarized potentials.
• Evoked EPSCs exhibited a late component, dependent on NMDA receptor activation, which was absent in mEPSCs and became more prominent with increased stimulation intensity. This component was sensitive to extracellular magnesium.
• NMDA receptor blockade (APV) and removal of extracellular Mg2+ affected mEPSC and evoked EPSC properties, particularly at depolarized potentials, with effects present as early as PN 3-5.

Conclusions:

• The basic kinetic properties of mEPSCs are established early in postnatal development (by PN 3-5) and remain largely unchanged during the first two postnatal weeks.
• NMDA receptor activation contributes to mEPSCs, and sensitivity to extracellular magnesium is present from PN 3-5.
• While unitary evoked EPSCs resemble mEPSCs, a distinct NMDA receptor-mediated late component emerges with increased stimulation intensity, highlighting the developmental emergence of NMDA receptor-dependent synaptic transmission.