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  • In addition to glutamatergic inputs the RTn integrates

    2019-12-03

    In addition to glutamatergic inputs, the RTn integrates cholinergic, serotonergic and noradrenergic synapses of fibers coming from nuclei located in the brainstem (Asanuma, 1992, Morrison and Foote, 1986, Pare et al., 1988) involved in the alternating firing mode and in the frequency changes of reticular neurons (Ben-Ari et al., 1976, Lee and McCormick, 1996, McCormick and Wang, 1991). The RTn is one of the nuclei with the highest density of D4 dopamine receptors (Mrzljak et al., 1996a) and one of the few thalamic nuclei that receives a dopaminergic innervation from the substantia nigra in both, rodents and primates (Anaya-Martinez et al., 2006, Garcia-Cabezas et al., 2009). In this context, it drew our attention the few number of studies that have analyzed the role of dopamine in the electrical activity of the RTn neurons in normal conditions (Gasca-Martinez et al., 2010) and in models of Parkinson’s disease, considering that destruction of the dopaminergic system increases the multidrug resistance transporter of the GAD67 in the RTn (Delfs et al., 1996) and that unilateral lesion of RTn dopaminergic fibers causes ipsilateral turns with the systemic application of apomorphine (Anaya-Martinez et al., 2006). Here, we recorded the in vivo unitary electrical activity of RTn neurons in Wistar rats under chloral hydrate anesthesia and studied the effects of local activation and blockade of D4 receptors in both conditions, normal and ipsilateral lesion of dopaminergic pathways.
    Results The average firing rate was 7.6 ± 0.65 spikes/s (0.42–40.5 range). We could identify two spiking patterns. Neurons displaying a mixed pattern of bursts of activity separated by tonic spiking (92/106, 89%), and neurons that showed a tonic-firing pattern (14/106, 13%; Fig. 1E). About 95% of the burst spiking neurons recorded in this work showed the classic acceleration-deceleration pattern which consists of an initial and progressive decrease in the duration of interspike intervals followed by an increasing in the duration of intervals; initial interespike interval lasted about 5–15 ms (Domich et al., 1985) (Fig. 1A–C). In contrast, 5% of the reticular burst spiking neurons did not show the acceleration-deceleration pattern (Fig. 1E). TC neurons burst morphology was different as compared with burst activity of RTn neurons; they lack the phenomenon of acceleration-deceleration (Fig. 1D). No correlation was found between the recording depth and the spiking patterns (Fig. 2B). The mean firing rate for the mixed pattern was 7.5 ± 0.74 spikes/s (0.42–40.5 range) and for the tonic firing pattern was 8.65 ± 0.92 spikes/s (0.98–15.1 range; Fig. 2D). The analysis of the coefficient of variance (CV) between neurons with mixed and tonic pattern did not show statistical differences (CV of mixed neurons: 1.42 ± 0.079, CV of tonic neurons 1.203 ± 0.11; p < 0.119, unpaired Student’s t-test). Data do not show. Only 11 (12%) of the 92 mixed pattern neurons, showed a spiking rate above 15 spikes/s (22.95 ± 2.05, 16.68–40.5 range). The burst index of these mixed pattern neurons was 0.49 ± 0.017 (0.49–0.95 range). No significant difference was found in the mean firing rate of both spiking patterns (p > 0.55, Student’s t-test; Fig. 2D). The maximal diameter of drug diffusion was 1.05 ± 0.04 mm, therefore, only those neurons within a radius of 0.52 mm from the tip of the recording electrode (Fig. 2A, C) were considered for statistical analysis.
    Discussion Despite the RTn having a motor sector which interchanges information with ventral anterior (VA) and ventral lateral (VL) nuclei of the motor thalamus and receives fibers coming from motor cortex and basal ganglia (Pinault, 2004, Pazo et al., 2013, Lam and Sherman, 2015, Villalobos et al., 2016) there are few works that analyses the relationship between RTn and Parkinson’s disease (Delfs et al., 1996, Anaya-Martinez et al., 2006). Furthermore, the RTn has one of the highest expression levels of D4-type receptors in the CNS (Mrzljak et al., 1996a).