Spermine modulates neuronal excitability and NMDA receptors in juvenile gerbil auditory thalamus

Medial geniculate body (MGB) neurons process synaptic inputs from auditory cortex. Corticothalamic stimulation evokes glutamatergic excitatory postsynaptic potentials (EPSPs) that vary markedly in amplitude and duration during development. The EPSP decay phase is prolonged during second postnatal week but then shortens, significantly, until adulthood. The EPSP prolongation depends on spermine interactions with a polyamine-sensitive site on receptors for N-methyl-D-aspartate (NMDA). We examined effects of spermine application on EPSPs, firing modes, and membrane properties in gerbil MGB neurons during the P14 period of highest polyamine sensitivity. Spermine slowed EPSP decay and promoted firing on EPSPs, without changing passive membrane properties. Spermine increased membrane rectification on depolarization, which is mediated by tetrodotoxin (TTX)-sensitive, persistent Na(+) conductance. As a result, spermine lowered threshold and increased tonic firing evoked with current injection by up to approximately 150%. These effects were concentration-dependent (ED(50)=100 microM), reversible, and eliminated by NMDA receptor antagonist, 2-amino-5-phosphonovalerate (APV). In contrast, spermine increased dV/dt of the low threshold Ca(2+) spike (LTS) and burst firing, evoked from hyperpolarized potentials. LTS enhancement was greater at -55 mV than at hyperpolarized potentials and did not result from persistent Na(+) conductance or glutamate receptor mechanisms. In summary, spermine increased excitability by modulating NMDA receptors in juvenile gerbil neurons.