DENDRITIC NA+ CHANNELS AMPLIFY EPSPS IN HIPPOCAMPAL CA1 PYRAMIDAL CELLS

1. Whole cell recordings were performed on the somata of CA1 pyramidal neurons in the rat hippocampal slice preparation. Remote synaptic eve nts were evoked by electrical stimulation of Schaffer collateral/commi ssural fibers in outer stratum radiatum. To isolate non-N-methyl-D-asp artate (NMDA)-mediated excitatory postsynaptic potentials (EPSPs), bat h solutions contained the NMDA receptor antagonist, D-2-amino-5-phosph onovaleric acid (D-APV; 30 mu M), the gamma-aminobutyric acid-A (GABA( A)) receptor antagonist, bicuculline (10 mu M), and the GABA(B) recept or antagonists, CGP 35348 (30 mu M) or, in some experiments, saclofen (100 mu M). 2. Local application of tetrodotoxin (TTX; 0.5-10 mu M) in to the proximal region of the apical dendrite reduced the peak amplitu de of somatically recorded EPSPs by 28% on average. In contrast to den dritic TTX application, injection of TTX into the axosomatic region of the recorded neuron reduced EPSP amplitude by only 12% on average. 3. Spill-over of dendritically applied TTX into stratum pyramidale or in to outer stratum radiatum was ruled out experimentally: somatic action potentials and field EPSPs recorded near the stimulation site in oute r stratum radiatum remained unaffected by local TTX application. 4. Va riations of somatic membrane potential revealed a strong voltage depen dence of EPSP reduction after dendritic TTX application with the effec t increasing substantially with membrane depolarization. Together with the field recordings from stratum radiatum, this finding argues stron gly against a predominantly presynaptic site of TTX action. 5. We ther efore ascribe the EPSP decrease after local TTX application to the pro ximal dendrite to suppression of dendritic Na+ channels, which we assu me to give rise to a noninactivating (persistent) Na+ current (I-NaP) in the subthreshold voltage range. Our data suggest that presumed dend ritic I-NaP produces considerable elevation of remote excitatory signa ls, thereby compensating for much of their electrotonic attenuation. 6 . The experimental findings were related to computer simulations perfo rmed on a reduced compartmental model of the CA1 neuron. Because the e xperimental evidence available so far yields only indirect clues on th e strength and distribution of I-NaP, we allowed considerable variatio ns in these parameters. We also varied both size and location of synap tic input. 7. The major conclusions drawn from these simulations are t he following: somatic I-NaP alone produces little EPSP enhancement; I- NaP density at the axon hillock/initial segment has to be at least twi ce the density at the soma to produce substantial EPSP amplification; depending on the density and distribution of dendritic I-NaP less than or equal to 80% of a remote synaptic potential arrives at the soma (c ompared with only 52% in a passive dendrite); synaptic potentials rece ive progressively more elevation by dendritic I-NaP the stronger they are; even if restricted to the proximal segment of the apical dendrite , I-NaP also affects dendritic processing at more distal segments; and spatial distribution rather than local density appears to be the most important parameter determining the role of dendritic I-NaP in synapt ic integration.