ELECTROPHYSIOLOGICAL PROPERTIES OF DORSAL RAPHE NUCLEUS NEURONS IN 5-HTT+/+ AND 5-HTT–/– MICE

摘要

A 5-HT transporter knockout (5-HTT–/–) mouse is a model of whole-life treatment with selective serotonin reuptake inhibitors (SSRIs). In our study, whole-cell patch clamp recordings were performed on dorsal raphe nucleus (DRN) neurons in order to classify these cells depending on their biophysical features. Three distinct types of DRN neurons were recorded in brain stem slices from adult 5-HTT+/+ and 5-HTT–/– mice, namely with a linear (type I) or rectifying (type II) I/V relationship, or a time dependent inward rectification (type III). Beside the I/V relationship, other electrophysiological characteristics of these neurons were analyzed (action potential duration and amplitude, membrane time constant of the voltage response to a 45–50 pA hyperpolarizing current pulse, afterhyperpolarisation duration and time constant, spike discharge frequency, current density). Action potential duration in type III neurons is shorter (3.8 ± 0.3 ms) than in type I and type II neurons (4.6 ± 0.6 ms, and 4.7 ± 0.8 ms respectively). Afterhyperpolarisation time constant is shorter in type III (1.2 ± 0.2 ms) than in type II neurons (2.4 ± 0.1 ms). For type I and type II, but not for type III neurons, a decrease of spike discharge frequency and an increase of inward current evoked by hyperpolarizing steps were recorded. Type I- and II-neurons are inhibited by 5-HT1A agonists being serotonergic neurons, while type III-neurons are not. These biophysical characteristics could explain the essential role played by 5-HT1A autoreceptors in the molecular mechanisms of depression.