Tetraethylammonium-Induced Synaptic Plasticity in Rat Neocortex

Recordings were obtained from neurons in layer II/III of slicesof rat frontal cortex maintained in vitro. We investigated whetherbrief application of the potassium channel blocker tetraethylammonium(TEA), which induces a novel form of synaptic plasticity inthe CA1 region of the hippocampus referred to as LTP_k evokessimilar responses in neocortex. Consistent with previous findings,TEA produced a persistent enhancement of excitatory transmission,which was independent of NMDA receptor activation but requiredthe activation of nifedipine-sensitive voltage-dependent Ca²⁺channels (VDCC), presumably the L-type. We also observed a persistentenhancement of presumptive Cl^–-dependent GABA_A receptor-mediatedtransmission. Enhancement of excitatory and inhibitory synaptictransmission did not require activation of synapses with electricalstimulation during TEA application. The enhancement of excitatory,but not inhibitory synaptic transmission, was blocked when theCa²⁺ chelator 1,2-bis(2-aminophenoxy)-ethane N,N,N',N'-tetraaceticacid (BAPTA) was included in the recording electrode. Undervoltage clamp conditions that minimized the activation of L-typechannels robust enhancement of both excitatory and inhibitorytransmission was still observed. No enhancement of excitatorysynaptic transmission was observed in the presence of NiCl₂,a putative T-type channel blocker. The possible involvementof kinase activation was studied by including the non-specificand competitive kinase inhibitor (±)-1-(5-isoquinolinesulfonyl)-2-methylpiperazinedihydrochloride (H-7) in the patch pipette. H-7 retarded thetime course and reduced the magnitude of the enhancement ofexcitatory transmission. These results suggest that TEA-inducedenhancement of excitatory transmission in the neocortex requiresentry of Ca²⁺ into the postsynaptic neuron via VDCCs and possiblythe activation of a kinase.