DISTRIBUTION AND FUNCTIONAL-PROPERTIES OF 5-HT3, RECEPTORS IN THE RAT HIPPOCAMPAL DENTATE GYRUS - A PATCH-CLAMP STUDY

1. In dentate gyrus of rat hippocampal slices two distinct types of neurons, principal excitatory neurons (granule cells) and local inhibitory neurons (basket cells), could be identified under Nomarski microscopy; I investigated the actions of serotonin using the whole-cell patch-clamp technique. The identification of the neurons was later confirmed by intracellular staining with Lucifer yellow. 2. In both basket cells and granule cells, whole-cell current recordings revealed spontaneous synaptic currents ranging from < 10 pA to > 200 pA in symmetrical Cl- conditions at a holding potential of -63 mV. These currents were blocked by 10 mu M bicuculline, indicating that they resulted from the spontaneous activation of GABAergic inputs (which had been morphologically described in both types of neurons). 3. By focal application of serotonin (2-50 mu M) to basket cells under current clamp I evoked a train of action potentials superimposed on a baseline membrane depolarization. Under voltage-clamp conditions serotonin evoked an inward current at a holding potential of -63 mV (currents were detectable in similar to 90% of basket cells studied). The inward current was accompanied by a multitude of small inward currents of short duration (<100 ms) that were found to be due to the stimulation by serotonin of nearby GABAergic presynaptic neurons innervating the recorded neuron. 4. In granule cells (total of 11 cells) serotonin did not produce any responses under conditions similar to those used for basket cells. The occurrence of bicuculline-sensitive spontaneous synaptic current events seemed to increase during the application of serotonin; this phenomenon reflected the excitatory action of seretonin exclusively on GABAergic interneurons. 5. The serotonin-induced inward currents in basket cells were mediated by the 5-HT3 receptor subtype because 1) they were blocked by either metoclopramide (10 mu M) or [3-alpha-tropanyl]-1H-indolecarboxylic acid ester (2 nM), the latter being a specific blocker for the 5-HT3 receptor subtype, and 2) almost similar currents were induced by the application of the selective 5-HT3 receptor agonist 2-methyl 5-HT (2-50 mu M) or 1-(m-chlorophenyl)-biguanide( 0.1-10 mu M).acological profile similar to that previously reported in other neural tissues. However, this response was unique in that the voltage-dependent blockade by Ca2+ and Mg2+ was observed when these were present at physiological concentrations in the external media.