Stereological estimations and neurochemical characterization of neurons expressing GABAA and GABAB receptors in the rat pedunculopontine and laterodorsal tegmental nuclei

To better understand GABAergic transmission at two targets of basal ganglia downstream projections, the pedunculopontine (PPN) and laterodorsal (LDT) tegmental nuclei, the anatomical localization of GABAA and GABAB receptors was investigated in both nuclei. Specifically, the total number of neurons expressing the GABAA receptor γ2 subunit (GABAAR γ2) and the GABAB receptor R2 subunit (GABAB R2) in PPN and LDT was estimated using stereological methods, and the neurochemical phenotype of cells expressing each subunit was also determined. The mean number of non-cholinergic cells expressing GABAAR γ2 was 9850 ± 1856 in the PPN and 8285 ± 962 in the LDT, whereas those expressing GABAB R2 were 7310 ± 1970 and 9170 ± 1900 in the PPN and LDT, respectively. In addition, all cholinergic neurons in both nuclei co-expressed GABAAR γ2 and 95–98% of them co-expressed GABAB R2. Triple labeling using in situ hybridization revealed that 77% of GAD67 mRNA-positive cells in the PPT and 49% in the LDT expressed GABAAR γ2, while 90% (PPN) and 65% (LDT) of Vglut2 mRNA-positive cells also expressed GABAAR γ2. In contrast, a similar proportion (~2/3) of glutamatergic and GABAergic cells co-expressed GABAB R2 in both nuclei. The heterogeneous distribution of GABAAR and GABABR among non-cholinergic cells in PPN and LDT may give rise to physiological differences within each neurochemical subpopulation. In addition, the dissimilar proportion of GABAAR γ2-expressing glutamatergic and GABAergic neurons in the PPN and LDT may contribute to some of the functional differences found between the two nuclei.

Comparative Study of the Distribution and Localization of Neuroglobin Expression in the Mammalian Brain: A Literature Review

Neuroglobin (Ngb) was recently identified as a member of the vertebrate hemoglobin family. Several studies have been conducted on Ngb in mammals, but none have compared its expression and localization among different mammals. This review compared the distribution and localization of Ngb expression and explained the different functions of Ngb in the brains of mammals. Intel’s integrated performance primitive (IPP) analysis was employed to obtain the expression levels in each region of the mammalian brain. Ngb is widely expressed in the adult yak brain and distributed in different areas, similar to its expression in cattle. The relative expression of the Ngb gene in the cerebral cortex (262.69 ± 9.19) was significantly higher than that in the cerebellar cortex (137.00 ± 7.29), hippocampus (1.00 ± 0.22), medulla oblongata (3.43 ± 0.76), striatum (7.65 ± 0.61) and olfactory bulb (2.14 ± 1.22). Findings in the rat brain showed low Ngb protein expression. The mouse brain showed Ngb over expression in a transgenic variant (Ngb-Tg), while in the human brain, the level of Ngb was higher in the hypothalamus, amygdala and pontine tegmental nuclei than in other parts of the brain. The expression levels, distribution and localization of Ngb differ across the brains of different mammals, so it is appropriate to explore the precise distribution and localization of Ngb before comparison or analysis in these mammals.

Nicotine Increases Spontaneous Glutamate Release in the Rostromedial Tegmental Nucleus

The rostromedial tegmental nucleus (RMTg) is a bilateral structure localized in the brainstem and comprise of mainly GABAergic neurons. One of the main functions of the RMTg is to regulate the activity of dopamine neurons of the mesoaccumbens pathway. Therefore, the RMTg has been proposed as a modulator of the reward system and adaptive behaviors associated to reward learning. The RMTg receives an important glutamatergic input from the lateral habenula. Also, it receives cholinergic inputs from the laterodorsal and pedunculopontine tegmental nuclei. Previously, it was reported that nicotine increases glutamate release, evoked by electric stimulation, in the RMTg nucleus. However, the mechanisms by which nicotine induces this effect were not explored. In the present work, we performed electrophysiological experiments in brainstem slices to study the effect of nicotine on spontaneous excitatory postsynaptic currents recorded from immunocytochemically identified RMTg neurons. Also, we used calcium imaging techniques to explore the effects of nicotine on multiple RMTg neurons simultaneously. We found that nicotine promotes the persistent release of glutamate through the activation of α7 nicotinic acetylcholine receptors present on glutamatergic afferents and by a mechanism involving calcium release from intracellular stores. Through these mechanisms, nicotine increases the excitability and synchronizes the activity of RMTg neurons. Our results suggest that the RMTg nucleus mediates the noxious effects of the nicotine, and it could be a potential therapeutic target against tobacco addiction.

Cholinergic Midbrain Afferents Modulate Striatal Circuits and Shape Encoding of Action Control

SummaryAssimilation of novel strategies into a consolidated action repertoire is a crucial function for behavioral adaptation and cognitive flexibility. Acetylcholine in the striatum plays a pivotal role in such adaptation and its release has been causally associated with the activity of cholinergic interneurons. Here we show that the midbrain, a previously unknown source of acetylcholine in the striatum, is a major contributor to cholinergic transmission in the striatal complex. Neurons of the pedunculopontine and laterodorsal tegmental nuclei synapse with striatal cholinergic interneurons and give rise to excitatory responses that, in turn, mediate inhibition of spiny projection neurons. Inhibition of acetylcholine release from midbrain terminals in the striatum impairs action shifting and mimics the effects observed following inhibition of acetylcholine release from striatal cholinergic interneurons. These results suggest the existence of two hierarchically-organized modes of cholinergic transmission in the striatum where cholinergic interneurons are modulated by cholinergic neurons of the midbrain.