Neuronal Entropy-Rate Feature of Entopeduncular Nucleus in Rat Model of Parkinson's Disease

Abstract

The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus, i.e. the entopeduncular nucleus (EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In both control subjects and subjects with 6-OHDA lesion of dopamine (DA) the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15 and 25 Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25 Hz. Our data establishes that the nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions such as movement disorders.

Keywords: 6-OHDA; Entropy; basal ganglia; dopamine; globus pallidus internal; rat.

Figure 1. Schematization of the basal ganglia circuitry

See introduction for discussion. The input nuclei of the BG consist of the STN and the striatum. The output nuclei of the BG are the GPi and the SNr. The BG input nuclei receive projection from the cortical area. The STN projects to the output nuclei through the glutamatergic hyperdirect pathway. The striatum projects to the output nuclei via two pathways: the direct pathway and the indirect pathway (through the GPe). White arrow: the inhibitory GABAergic; black arrow: excitatory glutamatergic projection; gray arrow: dopaminergic projection projections. DA: Dopamine, D1: receptors dopamine D1-like, D2: receptors dopamine D2-like, SNc: substantia nigra compacta, GPe: globus pallidus external (globus pallidus in rodent, GP), GPi: globus pallidus internal (entopedoncular nucleus in rodent, EPN), STN: subthalamic nucleus, Th: Thalamus.

Figure 2

(a) An illustration from the rat brain atlas of the EPN region at −2.5 mm posterior to bregma, 2.5 mm lateral to the midline and 7.8 to 8.0mm to the skull surface, localization of recording neurons for control (blue dots) and 6-OHDA lesioned rats (red dots), image modified from Paxinos and Watson (1986). (b) Histological verification showing (black arrows) the localization of a recording electrode by electric coagulation in thionine-stained coronal sections of the entopeduncular nucleus (EPN). (c) A representation of heart rate and (d) single neuronal activity for total duration of 3 s in the EPN of control (blue color) and 6-OHDA lesioned rats (red color) during microelectrode recordings.

Figure 3

The box plots illustrate the summary of changes in the firing rate (a), the ApEn values for all the neuronal activity between groups (b), the ApEn values for the neuronal activity less than <25Hz (c) and the ApEn values greater than >25 Hz (d) in the EPN of naïve control (N = 80) and 6-OHDA treated rats (N = 108). The central line of the box plots represents the median, the 25%–75% (interquartile) range, and the edge of the whiskers show the 5%-95% range.

Figure 4

(a): The curves illustrate the quantitative relation of ApEn values on the function of firing rate across the naïve control rats (N = 80; blue dots) and 6-OHDA treated rats (N = 108; red dots). Solid curves express the trend (Legendre polynomials, 4^th order) of ApEn as function of firing rate for control rats (blue curve) and 6-OHDA treated rats (red curve). Vertical lines indicate the range (25^th–75^th percentiles) of ApEn at different bins of frequency rates (bin size: 10Hz). Stars at the top indicate significant differences between controls and 6-OHDA subjects (P<0.05). (b) This figure indicates the distribution of cells as function of the firing rate in the control and 6-OHDA treated animals. Y axe expresses the percent over the cell population of each group.