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      Morphologic Characterization of Trigeminothalamic Terminal Arbors Arising From the Principal Nucleus in the Macaque

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          Abstract

          The ventral posterior medial nucleus (VPM) is amandatory relay for orofacial sensory information targeting the primary somatosensory cortex. We characterized the morphology of VPM axons arising in the principal trigeminal sensory nucleus (pV) through injections of biotinylated dextran amine (BDA) placed in pV of Macaca fascicularis and mulatta monkeys. Labeled terminals formed a patchy bilateral distribution. Within contralateral VPM, patches were found primarily, but not exclusively, within the laterally located, vertical segment, and in ipsilateral VPM, primarily, but not exclusively, in the medially located, horizontal segment. Two fiber types were labeled: thin and thick. Thin fibers were poorly branched and diffusely distributed. They were studded with small en passant boutons. Most labeled fibers were thick and they branched extensively to form distinctive terminal arbors decorated with numerous boutons that varied in size and shape. Quantitative analysis of thick fiber arbor features showed little difference between the sides, although contralateral boutons were significantly larger than ipsilateral ones. Bouton distribution with respect to counterstained somata suggests that proximal dendrites are their main target. Indeed, ultrastructural examination demonstrated that they provide large diameter dendrites with numerous contacts. Direct comparison of thick fiber terminal arbors to cytochrome oxidase (CO) staining revealed that these arbors are much smaller than individual CO-rich patches believed to designate rods containing discrete body area representations. Thus, each terminal arbor appears to heavily innervate a small number of VPM neurons within a rod. This relationship would serve to maintain relatively small receptive fields within the topographic representation of the face.

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          On the actions that one nerve cell can have on another: distinguishing "drivers" from "modulators".

          When one nerve cell acts on another, its postsynaptic effect can vary greatly. In sensory systems, inputs from "drivers" can be differentiated from those of "modulators." The driver can be identified as the transmitter of receptive field properties; the modulator can be identified as altering the probability of certain aspects of that transmission. Where receptive fields are not available, the distinction is more difficult and currently is undefined. We use the visual pathways, particularly the thalamic geniculate relay for which much relevant evidence is available, to explore ways in which drivers can be distinguished from modulators. The extent to which the distinction may apply first to other parts of the thalamus and then, possibly, to other parts of the brain is considered. We suggest the following distinctions: Cross-correlograms from driver inputs have sharper peaks than those from modulators; there are likely to be few drivers but many modulators for any one cell; and drivers are likely to act only through ionotropic receptors having a fast postsynaptic effect whereas modulators also are likely to activate metabotropic receptors having a slow and prolonged postsynaptic effect.
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            Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry.

            Endogenous cytochrome oxidase activity within the mitochondria of neurons and neuropil was demonstrated histochemically under normal and experimental conditions. Since enzymatic changes were noted with chronic neuronal inactivity in the auditory system (Wong-Riley et al), the present study sought to examine functionally induced enzymatic changes in the visual system of kittens. Eight kittens were used experimentally: 5 had monocular lid suture for varying periods of time; one had binocular lid suture followed by monocular suture followed by binocular opening; two had monocular enucleation. All initial procedures were performed before eye opening. Materials from other normal kittens and cats were also used as controls. At the end of the experiments, the animals were perfused with aldehyde solutions and frozen sections of the brains were incubated for cytochrome oxidase activity (a detailed protocol was outlined). The results indicated that the deprivation caused by monocular suture produced a decrease in the cytochrome oxidase staining of the binocular segment of the deprived geniculate laminae. Enucleation yielded a greater decrease in the cytochrome oxidase activity in the affected geniculate laminae. However, the staining in the 'normal' lamina extended across the interlaminar border to include a row of surviving large cells in the 'denervated' lamina. The staining of the monocular segment appeared not to be affected by lid suture, but was decreased by enucleation. At the cortical level, lamina IV in area 17 of normal cats was stained darkly as a continuous band. Following lid suture, this pattern was replaced in part by alternating columns of light and dark staining, suggestive of ocular dominance columns. Thus, a decrease in neuronal activity due to reduced visual stimulation or destruction of the primary afferent nerves led to a significant decrease in the level of oxidative enzyme activity one to several synapses away.
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              Functioning of Circuits Connecting Thalamus and Cortex.

              Glutamatergic pathways in thalamus and cortex are divided into two distinct classes: driver, which carries the main information between cells, and modulator, which modifies how driver inputs function. Identifying driver inputs helps to reveal functional computational circuits, and one set of such circuits identified by this approach are cortico-thalamo-cortical (or transthalamic corticocortical) circuits. This, in turn, leads to the conclusion that there are two types of thalamic relay: first order nuclei (such as the lateral geniculate nucleus) that relay driver input from a subcortical source (i.e., retina), and higher order nuclei (such as the pulvinar) which are involved in these transthalamic pathways by relaying driver input from layer 5 of one cortical area to another. This thalamic division is also seen in other sensory pathways and beyond these so that most of thalamus by volume consists of higher-order relays. Many, and perhaps all, direct driver connections between cortical areas are paralleled by an indirect cortico-thalamo-cortical (transthalamic) driver route involving higher order thalamic relays. Such thalamic relays represent a heretofore unappreciated role in cortical functioning, and this assessment challenges and extends conventional views regarding both the role of thalamus and mechanisms of corticocortical communication. Finally, many and perhaps the vast majority of driver inputs relayed through thalamus arrive via branching axons, with extrathalamic targets often being subcortical motor centers. This raises the possibility that inputs relayed by thalamus to cortex also serve as efference copies, and this may represent an important feature of information relayed up the cortical hierarchy via transthalamic circuits. © 2017 American Physiological Society. Compr Physiol 7:713-739, 2017.
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                Author and article information

                Contributors
                Journal
                Front Neuroanat
                Front. Neuroanat.
                Frontiers in Neuroanatomy
                Frontiers Media S.A.
                1662-5129
                16 September 2020
                2020
                : 14
                : 562673
                Affiliations
                [1] 1Department of Occupational Therapy, University of Mississippi Medical Center , Jackson, MS, United States
                [2] 2Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center , Jackson, MS, United States
                [3] 3Department of Ophthalmology, University of Mississippi Medical Center , Jackson, MS, United States
                [4] 4Department of Neurology, University of Mississippi Medical Center , Jackson, MS, United States
                Author notes

                Edited by: Kathleen S. Rockland, Boston University, United States

                Reviewed by: Izumi Sugihara, Tokyo Medical and Dental University, Japan; Martha E. Bickford, University of Louisville, United States; Diana Casas-Torremocha, Institut de Recerca Biomèdica August Pi i Sunyer (IDIBAPS), Spain

                *Correspondence: Susan Warren swarren@ 123456umc.edu

                Dona Lee E. Andrew has retired but can be contacted at mailto:dleandrew@aol.com

                Article
                10.3389/fnana.2020.562673
                7525072
                130e242e-7b37-46b6-ba44-727cd5af3015
                Copyright © 2020 Andrew, May and Warren.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 May 2020
                : 18 August 2020
                Page count
                Figures: 10, Tables: 0, Equations: 0, References: 58, Pages: 16, Words: 11354
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Funded by: Benign Essential Blepharospasm Research Foundation 10.13039/100008537
                Categories
                Neuroscience
                Original Research

                Neurosciences
                somatosensory,trigeminal,thalamus,oral-facial,ventral posterior medial
                Neurosciences
                somatosensory, trigeminal, thalamus, oral-facial, ventral posterior medial

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