Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia.

The basal ganglia (BG) integrate inputs from diverse sensorimotor, limbic, and associative regions to guide action-selection and goal-directed behaviors. The entopeduncular nucleus (EP) is a major BG output nucleus and has been suggested to channel signals from distinct BG nuclei to target regions involved in diverse functions. Here we use single-cell transcriptional and molecular analyses to demonstrate that the EP contains at least three classes of projection neurons-glutamate/GABA co-releasing somatostatin neurons, glutamatergic parvalbumin neurons, and GABAergic parvalbumin neurons. These classes comprise functionally and anatomically distinct output pathways that differentially affect EP target regions, such as the lateral habenula (LHb) and thalamus. Furthermore, LHb- and thalamic-projecting EP neurons are differentially innervated by subclasses of striatal and pallidal neurons. Therefore, we identify previously unknown subdivisions within the EP and reveal the existence of cascading, molecularly distinct projections through striatum and globus pallidus to EP targets within epithalamus and thalamus.

Immunohistochemical study on the neuronal diversity and three-dimensional organization of the mouse entopeduncular nucleus.

The entopeduncular nucleus (EPN) is one of the major output nuclei of the basal ganglia in rodents. Previous studies have divided it into rostral and caudal halves, with the former containing somatostatin (SOM)-immunoreactive neurons and the latter dominated by parvalbumin (PV)-containing neurons, respectively. However, it is unclear whether this simple rostrocaudal segmentation is appropriate, and the possibility of the existence of other neuronal populations remains to be investigated. In this study the cytoarchitecture of the mouse EPN was analyzed immunohistochemically. Substance P (SP)-immunoreactivity determined the extent of the EPN, which was 800 µm-long along the rostrocaudal axis. PV-positive neurons were concentrated in the caudal two-thirds of this range. PV-negative neurons were abundant in the rostral half but were further located caudally around the PV neuron-rich core. PV(+)/SOM(-) and PV(-)/SOM(+) neurons constituted 28.6% and 45.7% of EPN neurons, respectively, whereas the remaining population (25.7%) exhibited neither immunoreactivity. Eleven percent of EPN neurons lacked immunoreactivity for glutamic acid decarboxylase, indicating their non-GABAergic nature. Three-dimensional reconstruction revealed that PV-rich/SP-poor core was surrounded by PV-poor/SP-rich shell region. Therefore, presumptive thalamus-targeting PV neurons are outnumbered by other populations, and the regional heterogeneity shown here might be related to functionally distinct pathways through the basal ganglia.

Spontaneous neural activity of the anterodorsal lobe and entopeduncular nucleus in adult zebrafish: a putative homologue of hippocampal sharp waves.

Spontaneous neural activity is instrumental in the formation and maintenance of neural circuits that govern behavior. In mammals, spontaneous activity is observed in the spinal cord, brainstem, diencephalon, and neocortex, and has been most extensively studied in the hippocampus. Using whole-brain in vitro recordings we establish the presence of spontaneous activity in two regions of the zebrafish telenchephalon: the entopeduncular nucleus (EN) and the anterodorsal lobe (ADL). The ADL is part of the lateral telencephalic pallium, an area hypothesized to be functionally equivalent to the mammalian hippocampus. In contrast, the EN has been hypothesized to be equivalent to the mammalian basal ganglia. The observed spontaneous activity is GABA modulated, sensitive to glutamate and chloride transporter antagonists, and is abolished by sodium pump blockers; moreover, the spontaneous activity in the ADL is a slow multiband event (∼100 ms) characterized by an embedded fast ripple wave (∼150-180 Hz). Thus, the spontaneous activity in the ADL shares physiological features of hippocampal sharp waves in rodents. We suggest that this spontaneous activity is important for the formation and maintenance of neural circuits in zebrafish and argue that applying techniques unique to the fish may open novel routes to understand the function of spontaneous activity in mammals.

Analysis of the morphological substrate for information processing in the pallidal nuclear complex of the dog brain in terms of the organizational characteristics of its afferent projections.

Axonal transport of retrograde markers was used to study the distribution of the afferent projections of the nuclei of the pallidal complex (the globus pallidus, the entopeduncular nucleus, and the ventral pallidum) from functionally diverse cortical and subcortical structures (cortical fields, substantia nigra, ventral tegmental field, and thalamus) in the dog brain. The results were used to analyze the morphological aspects both of the functional heterogeneity of the pallidum and integrative information processing, which underlie the mechanisms of adaptive behavior.

Study of projections from the entopeduncular nucleus to the thalamus of the rat.

The entopeduncular nucleus (EP) is a major outflow nucleus of the basal ganglia and innervates the lateral habenula, parafascicular, pedunculopontine, ventrolateral (VL), ventromedial (VM), and mediodorsal thalamic nuclei. This study investigated the morphology of single axons of entopeduncular neurons projecting to the motor thalamus by placing small injections of dextran biotin into the EP and reconstructing drawings of single axons from serial sections. There were two populations of entopeduncular-thalamic projection axons: those that projected only to the motor thalamus (VL and VM) and those that projected to both the motor thalamus and other nuclei (e.g., the habenula). The neurochemistry of EP neurons projecting to the thalamus was investigated by injecting the retrograde tracer FluoroGold into the VL and VM thalamic nuclei to retrogradely fill entopeduncular projection neurons. These were subsequently immunohistochemically labeled for choline acetyl transferase, gamma-aminobutyric acid (GABA), and glutamate. Consistent with previous studies, significant proportions of these neurons were GABA immunoreactive. In addition, approximately half of the entopeduncular-thalamic projecting neurons were found to be cholinergic. This excitatory input is most likely derived from axons that branch as they pass through the motor thalamus to the lateral habenula.