Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.

A Zona Incerta no sagüi (Callithrix jacchus): Análise Citoarquitetônica, Neuroquímica e Projeção Retiniana

The retinal projections in mammals usually reach, classically, three major functional systems: the primary visual system, the accessory optic system, and the circadian timing system. But the retinal projections also reach areas classically considered non-visual, one of which groups the neurons of the zona incerta (ZI), target this study. The primary visual system includes thalamic lateral geniculate complex is formed by the dorsal lateral geniculate nucleus, intergeniculate leaflet and the ventral lateral geniculate nucleus and other Components. The accessory optic system is composed of the small nuclei: nuclei terminal dorsal, lateral, medial and the interstitial nucleus of the superior posterior fasciculus. These nuclei are involved in visuo-motor activities. The circadian timing system is comprised of the suprachiasmatic nucleus of the hypothalamus, that act as master circadian pacemaker, entraining pathways and efferents pathways to the efectors, and the intergeniculate leaflet, that seems to act as a modulator of the pacemaker. The retinal projections too reach classically considered non-visual areas, including the zona incerta. This region is localized in the ventral thalamus and has been implicated in various functional properties including nociceptive and somatosensory processing, motor response, sociosexual behaviour, feeding and drinking, in symptoms of neurodegenerative diseases, arousal and attention. It also displays connection with several areas of central nervous system. The aim of this study was characterize the retinal projection in the zona incerta of Callithrix jacchus (sagüi), a primate of the New World through the anterograde axonal transport of the cholera toxin subunit b and analyze the citoarchicteture using Nissl and NeuN, and neurochemical substances such as serotonin, GABA, VIP, VP, GFAP and binding-calcium proteins. The zona incerta showed a different division of the literature in citoarquitetura, both by means of Nissl as neurochemical by NeuN, with a subdivision ventrolateral and dorsomedial. The neurochemical to the other substances corroborate with this subdivision. The GFAP was almost completely negative for the zona incerta, result non evidenced in previous studies yet. The 16 retinal projection in sagüi, unlike other primates and rodents, reached the caudal portion only. This work helps to make further studies are conducted based on this subdivision and the localization of the neurochemical substances associated with possible behaviors that the zona incerta is involved

O Núcleo genuíno lateral dorsal do tálamo do sagüi (callithrix jacchus): Pprojeção retiniana, caracterização citoarquitetônica e neuroquimica da principal estação visual primária.

The thalamus plays an important role in the sensorial processing information, in this particular case, the visual information. Several neuronal groups have been characterized as conductors and processors of important sensorial information to the cerebral cortex. The lateral geniculate complex is one to them, and appears as a group very studied once it is responsible, in almost all totality, for the processing of visual information. Among the nuclei that constitute the lateral geniculate complex we highlight the dorsal lateral geniculate nucleus of the thalamus (DLG), the main thalamic relay for the visual information. This nucleus is located rostral and lateral to medial geniculate nucleus and ventral to thalamic pulvinar nucleus in most of the mammals. In the primates humans and non-humans, it presents as a laminate structure, arranged in layers, when observed in coronal sections. The objective of this work was to do a mapping of the retinal projections and a citoarchictetonic and neurochemical characterization of DLG in the marmoset (Callithrix jacchus), a New World primate. The retinal projections were traced by anterograde transport of subunit b of cholera toxin (CTb), the citoarchicteture was described by Nissl method, and to neurochemical characterization immunohistochemicals technical were used to examine the main neurotransmitters and neuroatives substances present in this neural center. In DGL of marmoset thalamus, in coronal sections labeled by Nissl method, was possible to visualize the division of this nucleus in four layers divided in two portions: magnocellular and parvocellular. The retinal projections were present being visualized fibers and terminals immunorreactives to CTb (IR-CTb) in the DLG ipsilateral and contralateral. And through the immunohistochemicals techniques was observed that DLG contain cells, fibers and/or terminals immunoreactives against neuronal nuclear protein, subunits of AMPA 15 glutamate receptors (GluR1, GluR2/3, GluR4), choline acetyltransferase, serotonin, glutamic acid decarboxylase, binding calcium proteins (calbindin, parvalbumin and calretinin), vasopressin, vasoactive intestinal polypeptide, and an astrocyte protein, glial fibrillary acidic protein.

Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.