Fourier analysis applied to the study of the electrical activity of midbrain dopaminergic neurons

Abstract

In this study, electrophysiological techniques and computational methods were used to investigate the effect of the selective serotonin reuptake inhibitors fluvoxamine paroxetine sertraline and citalopram on the basal activity of dopamine (DA) neurons in the ventral tegmental area. Acute injection of fluvoxamine paroxetine sertraline and citalopram (20-1280 µg/kg i.v) caused a dose-dependent inhibition of some ventral tegmental area DA neurons but it did not affect the basal firing rate of other DA cells. A Fast-Fourier-Transformation based analysis of the basal activity of 45 ventral tegmental area DA neurons showed a positive correlation between the value of a functional operator (Ψ) equivalent to the density-power­spectrum of the signals and the degree of selective serotonin reuptake inhibitors-induced inhibition of ventral tegmental area DA cells. All ventral tegmental area DA neurons sampled were subdivided into two subclasses: (A) neurons with no changes in their basal firing rate and (B) neurons showing an approximately linear inhibitory effect in response to selective serotonin reuptake inhibitors. The neurons belonging to the subclass A showed a more regular behavior of the interspike interval functions corresponding to lower values detected by the functional operator Ψ whereas the neurons belonging to the subclass B showed a less regular behavior of interspike interval functions corresponding to higher Ψ values detected by the same functional operator. SSRIs also caused a dose-dependent increase of the percentage of spikes occurring in bursts in neurons belonging to subclass A (low values of Ψ) whereas the mean basal firing rate of these cells was not affected. Moreover administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.25-80 µg/kg i.v) increased the firing rate of midbrain DA neurons with higher ‘P values. It is suggested that this difference in density-power-spectrum could reflect the asymmetry of serotonergic input to the ventral tegmental area DA neurons and the differential effects of selective serotonin reuptake inhibitors and of 8-OH-DPAT on these neurons might depend on the characteristics of their basal firing mode.