Endocannabinoids and Dopamine Balance Basal Ganglia Output

The entopeduncular nucleus is one of the basal ganglia's output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the Striatum and the globus pallidus, together with glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all these primary afferents to the entopeduncular nucleus. Our results suggest that the interplay between dopamine and endocannabinoids determines the balance between direct pathway (striatum) and indirect pathway (globus pallidus) in entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoid diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.

Deep Learning-Supported Cytoarchitectonic Mapping of the Human Lateral Geniculate Body in the BigBrain

The human lateral geniculate body (LGB) with its six sickle shaped layers (lam) represents the principal thalamic relay nucleus for the visual system. Cytoarchitectonic analysis serves as the groundtruth for multimodal approaches and studies exploring its function. This technique, however, requires experienced knowledge about human neuroanatomy and is costly in terms of time. Here we mapped the six layers of the LGB manually in serial, histological sections of the BigBrain, a high-resolution model of the human brain, whereby their extent was manually labeled in every 30th section in both hemispheres. These maps were then used to train a deep learning algorithm in order to predict the borders on sections in-between these sections. These delineations needed to be performed in 1 µm scans of the tissue sections, for which no exact cross-section alignment is available. Due to the size and number of analyzed sections, this requires to employ high-performance computing. Based on the serial section delineations, high-resolution 3D reconstruction was performed at 20 µm isotropic resolution of the BigBrain model. The 3D reconstruction shows the shape of the human LGB and its sublayers for the first time at cellular precision. It represents a use case to study other complex structures, to visualize their shape and relationship to neighboring structures. Finally, our results could provide reference data of the LGB for modeling and simulation to investigate the dynamics of signal transduction in the visual system.

Dynamic Transitions of Epilepsy Waveforms Induced by Astrocyte Dysfunction and Electrical Stimulation

Experimental studies have shown that astrocytes participate in epilepsy through inducing the release of glutamate. Meanwhile, considering the disinhibition circuit among inhibitory neuronal populations with different time scales and the feedforward inhibition connection from thalamic relay nucleus to cortical inhibitory neuronal population, here, we propose a modified thalamocortical field model to systematically investigate the mechanism of epilepsy. Firstly, our results show that rich firing activities can be induced by astrocyte dysfunction, including high or low saturated state, high- or low-frequency clonic, spike-wave discharge (SWD), and tonic. More importantly, with the enhancement of feedforward inhibition connection, SWD and tonic oscillations will disappear. In other words, all these pathological waveforms can be suppressed or eliminated. Then, we explore the control effects after different external stimulations applying to thalamic neuronal population. We find that single-pulse stimulation can not only suppress but also induce pathological firing patterns, such as SWD, tonic, and clonic oscillations. And we further verify that deep brain stimulation can control absence epilepsy by regulating the amplitude and pulse width of stimulation. In addition, based on our modified model, 3 : 2 coordinated reset stimulation strategies with different intensities are compared and a more effective and safer stimulation mode is proposed. Our conclusions are expected to give more theoretical insights into the treatment of epilepsy.

Endocannabinoids and dopamine balance basal ganglia output

The entopeduncular nucleus is one of the basal ganglia’s output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the striatum and the globus pallidus and glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all the primary afferents to the entopeduncular nucleus. Our results suggest that dopamine-endocannabinoids interplay determines the balance of the direct or indirect dominance of entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoids diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.

Non-thalamic origin of zebrafish sensory relay nucleus: convergent evolution of visual pathways in amniotes and teleosts

Ascending visual projections similar to the mammalian thalamocortical pathway are found in a wide range of vertebrate species, but their homologous relationship is debated. To get better insights into their evolutionary origin, we examined the developmental origin of a visual relay nucleus in zebrafish (a teleost fish). Similarly to the tectofugal visual thalamic nuclei in amniotes, the lateral part of the preglomerular complex (PG) in teleosts receives tectal information and projects to the pallium. However, our cell lineage study reveals that the majority of PG cells are derived from the midbrain, not from the forebrain. We also demonstrate that the PG projection neurons develop gradually until juvenile stage, unlike the thalamic projection neurons. Our data suggest that teleost PG is not homologous to the amniote thalamus and that thalamocortical-like projections can evolve from a non-forebrain cell population. Thus, sensory pathways in vertebrate brains exhibit a surprising degree of variation.

Peter Orlebar Bishop. 14 June 1917—3 June 2012

Peter Orlebar Bishop was an Australian neurophysiologist renowned for his ingenious quantitative approach to the study of the mammalian visual system and his great ability to attract a large number of talented people to visual research. Peter’s research was based on specially designed, precise instrumentation and data quantification applied mainly to analysis of the response properties of single neurones in the principal dorsal thalamic visual relay nucleus, the dorsal lateral geniculate nucleus (LGNd) and the primary visual cortex. This quantitative bent was evident throughout Peter’s entire research career: starting with the design and construction of innovative DC amplifiers; to his quantitative analysis of optics, ‘schematic eye’ for the cat, which rivalled Gullstrand’s schematic eye for humans; to creating and demonstrating validity of the concept of ‘projection lines’ in the representation of contralateral visual field in different cellular layers of the LGNd of mammals with frontally positioned eyes and discovery of massive binocular input to single LGNd neurones. Peter’s engineering approach was probably at its heuristic peak when it revealed many details of binocular interactions at the level of single neurones in the primary visual cortex—the interactions which appear to underpin overall mechanisms underlying stereopsis, the high precision binocular depth sense.

Peter Orlebar Bishop 1917–2012

Peter Orlebar Bishop was an Australian neurophysiologist renowned for his ingenious quantitative approach to study of the mammalian visual system and great ability to attract a large number of talented people to visual research. Peter's research was based on specially designed, precise instrumentation and data quantification applied mainly to analysis of the response properties of single neurones in the principal dorsal thalamic visual relay nucleus, the dorsal lateral geniculate nucleus (LGNd) and the primary visual cortex. This quantitative bent was evident throughout Bishop's entire research career:starting with the design and construction of innovative DC amplifiers; through to his quantitative analysis of optics—‘schematic eye' for the cat, which rivaled Gullstrand's schematic eye for humans; to creating and demonstrating validity of the concept of ‘projection lines' in the representation of contralateral visual field in different cellular layers of the LGNd of mammals with frontally positioned eyes and discovery of a very substantial binocular input to single LGNd neurones. The engineering approach of Peter was probably at its heuristic peak when it revealed many details of binocular interactions at the level of single neurones in the primary visual cortex—the interactions that appear to underpin overall mechanisms underlying stereopsis, the high precision binocular depth sense.

Changes in Otx2 and Parvalbumin Immunoreactivity in the Superior Colliculus in the Platelet-Derived Growth Factor Receptor-βKnockout Mice

The superior colliculus (SC), a relay nucleus in the subcortical visual pathways, is implicated in socioemotional behaviors. Homeoprotein Otx2 andβsubunit of receptors of platelet-derived growth factor (PDGFR-β) have been suggested to play an important role in development of the visual system and development and maturation of GABAergic neurons. Although PDGFR-β-knockout (KO) mice displayed socio-emotional deficits associated with parvalbumin (PV-)immunoreactive (IR) neurons, their anatomical bases in the SC were unknown. In the present study, Otx2 and PV-immunolabeling in the adult mouse SC were investigated in the PDGFR-βKO mice. Although there were no differences in distribution patterns of Otx2 and PV-IR cells between the wild type and PDGFR-βKO mice, the mean numbers of both of the Otx2- and PV-IR cells were significantly reduced in the PDGFR-βKO mice. Furthermore, average diameters of Otx2- and PV-IR cells were significantly reduced in the PDGFR-βKO mice. These findings suggest that PDGFR-βplays a critical role in the functional development of the SC through its effects on Otx2- and PV-IR cells, provided specific roles of Otx2 protein and PV-IR cells in the development of SC neurons and visual information processing, respectively.