TY - JOUR
T1 - Differential presynaptic modulation of excitatory and inhibitory autaptic currents in cultured hippocampal neurons
AU - Thio, Liu Lin
AU - Yamada, Kelvin A.
PY - 2004/6/25
Y1 - 2004/6/25
N2 - Short-term synaptic plasticity has an important role in higher cortical function. Hyperpolarization may effect a form of short-term plasticity by promoting recovery from sodium channel inactivation or by activating axonal A-type potassium channels. To determine whether one or both processes occur, we examined the effect of hyperpolarizing prepulses on autaptic currents in cultured postnatal rat hippocampal neurons. As expected of enhanced recovery from sodium channel inactivation, hyperpolarizing prepulses reversibly increased fast excitatory autaptic currents (eacs) mediated by α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptors (AMPARs), slow eacs mediated by N-methyl-D-aspartate receptors (NMDARs), and inhibitory autaptic currents (iacs) mediated by γ-aminobutyric acidA receptors (GABA ARs). Hyperpolarizing prepulses augmented nearly all fast and slow eacs but only half of the iacs. This change occurred without a change in autaptic current kinetics. Of note, hyperpolarizing prepulses did not significantly reduce autaptic currents in any neuron studied. The rapidly dissociating competitive antagonists kynurenate and L-2-amino-5-phosphonovaleric acid (LAPV) inhibited fast and slow eacs, respectively, to the same extent with and without a hyperpolarizing prepulse. In addition, hyperpolarizing prepulses revealed a slow eac even after the slow eac evoked without a prepulse was completely blocked by the open channel blocker, (+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801). Finally, hyperpolarizing prepulses did not alter currents evoked by exogenous applications of glutamate and GABA. These findings suggest that hyperpolarizing prepulses preferentially enhance eacs over iacs, and that they do so, in part, by overcoming conduction block or by activating silent synapses.
AB - Short-term synaptic plasticity has an important role in higher cortical function. Hyperpolarization may effect a form of short-term plasticity by promoting recovery from sodium channel inactivation or by activating axonal A-type potassium channels. To determine whether one or both processes occur, we examined the effect of hyperpolarizing prepulses on autaptic currents in cultured postnatal rat hippocampal neurons. As expected of enhanced recovery from sodium channel inactivation, hyperpolarizing prepulses reversibly increased fast excitatory autaptic currents (eacs) mediated by α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptors (AMPARs), slow eacs mediated by N-methyl-D-aspartate receptors (NMDARs), and inhibitory autaptic currents (iacs) mediated by γ-aminobutyric acidA receptors (GABA ARs). Hyperpolarizing prepulses augmented nearly all fast and slow eacs but only half of the iacs. This change occurred without a change in autaptic current kinetics. Of note, hyperpolarizing prepulses did not significantly reduce autaptic currents in any neuron studied. The rapidly dissociating competitive antagonists kynurenate and L-2-amino-5-phosphonovaleric acid (LAPV) inhibited fast and slow eacs, respectively, to the same extent with and without a hyperpolarizing prepulse. In addition, hyperpolarizing prepulses revealed a slow eac even after the slow eac evoked without a prepulse was completely blocked by the open channel blocker, (+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801). Finally, hyperpolarizing prepulses did not alter currents evoked by exogenous applications of glutamate and GABA. These findings suggest that hyperpolarizing prepulses preferentially enhance eacs over iacs, and that they do so, in part, by overcoming conduction block or by activating silent synapses.
KW - Conduction block
KW - Excitable membranes and synaptic transmission
KW - Hyperpolarizing prepulse
KW - Presynaptic mechanisms
KW - Short-term plasticity
KW - Silent synapse
KW - Spillover
UR - http://www.scopus.com/inward/record.url?scp=2442446905&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2004.02.077
DO - 10.1016/j.brainres.2004.02.077
M3 - Article
C2 - 15158157
AN - SCOPUS:2442446905
SN - 0006-8993
VL - 1012
SP - 22
EP - 28
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -