Personne : Parent, André
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Université Laval. Faculté de médecine
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- PublicationRestreintAxonal branching pattern of neurons of the subthalamic nucleus in primates(Wistar Institute of Anatomy and Biology, 2000-07-05) Sato, Fumi; Parent, Martin; Parent, André; Lévesque, MartinAxonal projections arising from the subthalamic nucleus (STN) in cynomolgus monkeys (Macaca fascicularis) were traced after labeling small pools (5-15 cells) of neurons with biotinylated dextran amine. Seventy-five single axons were reconstructed from serial sagittal sections with a camera lucida. Most of the STN labeled cells displayed five to eight long, sparsely spined dendrites that arborized mostly along the main axis of the nucleus. Based on their axonal targets, five distinct types of STN projection neurons have been identified: 1) neurons projecting to the substantia nigra pars reticulata (SNr), the internal (GPi) and external (GPe) segments of the globus pallidus (21.3%); 2) neurons targeting SNr and GPe (2.7%); 3) neurons projecting to GPi and GPe (48%); 4) neurons targeting GPe only (10.7 %); and 5) neurons with axons that coursed toward the sriatum, but whose terminal arborization could not be visualized in detail (17.3%). Axons of the first two types bifurcated into rostral subthalamopallidal and caudal pallidonigral branches. However, the majority of STN axons had only a single branch that coursed rostrally toward the pallidum and striatum. These results reveal that, in contrast to current beliefs, the primate STN is not a monolithic entity. This nucleus harbors several subtypes of projection neurons, each endowed with a highly patterned set of collaterals. This organization allows STN neurons to exert a multifarious effect not only on the GPe, with which the STN is reciprocally connected, but also on the two major output structures of the basal ganglia, the SNr and the GPi.
- PublicationAccès libreStriatal neurons expressing D1 and D2 receptors are morphologically distinct and differently affected by dopamine denervation in mice(Nature Publishing Group, 2017-01-27) Gagnon, Dave; De Koninck, Yves; Beaulieu, Jean Martin; Sánchez, Maria Gabriela; Parent, Martin; Petryszyn, Sarah; Parent, André; Bories, CyrilThe loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease.
- PublicationRestreintJules Bernard Luys : a singular figure of 19th Century neurology(Cambridge University Press, 2002-08-01) Parent, Martin; Parent, André; Leroux-Hugon, VéroniqueJules Bernard Luys was a highly industrious and dedicated French investigator who made important contributions to the fields of neuroanatomy and neuropsychiatry in the second half of the 19th century. His name is still eponymically attached to the subthalamic nucleus and the centre médian nucleus, two structures that are at the center of our current thinking about the functional organization of the basal ganglia and the pathophysiology of Parkinson’s disease. While developing a highly original view of the anatomical and functional organization of the human brain, Luys contributed significantly to our knowledge of the neuropathological and clinical aspects of mental illnesses. Luys devoted the last part of his career to hysteria and hypnosis, engaging himself in experiments as extravagant as the action of medication at distance. In doing so, he became perhaps the most highly caricatured example of the fascination that hysteria exerted upon various renowned neurologists at the end of the 19th century. This paper briefly summarizes the contribution of this remarkable figure of the history of neurology.
- PublicationRestreintAsynaptic feature and heterogeneous distribution of the cholinergic innervation of the globus pallidus in primates(Springer Verlag, 2014-12-19) Parent, Martin; Eid, Lara; Parent, AndréThe internal (GPi) and external (GPe) segments of the primate globus pallidus receive a significant cholinergic (ACh) innervation from the brainstem pedunculopontine tegmental nucleus. The present immunohistochemical study describes this innervation in the squirrel monkey (Saimiri sciureus), as visualized with an antibody raised against choline acetyltransferase (ChAT). At the light microscopic level, unbiased stereological quantification of ChAT positive (?) axon varicosities reveals a significantly lower density of innervation in GPi (0.26 ± 0.03 9 106) than in GPe (0.47 ± 0.07 9 106 varicosities/mm3 of tissue), with the anterior half of both segments more densely innervated than the posterior half. Neuronal density of GPi (3.00 ± 0.13 9 103 neurons/mm3) and GPe (3.62 ± 0.22 9 103 neurons/mm3) yields a mean ratio of ChAT? axon varicosities per pallidal neuron of 74 ± 10 in the GPi and 128 ± 28 in the GPe. At the electron microscopic level, the pallidal ChAT? axon varicosities are significantly smaller than their unlabeled counterparts, but are comparable in size and shape in the two pallidal segments. Only a minority of ChAT? varicosities displays a synaptic specialization (12 % in the GPi and 17 % in the GPe); these scarce synaptic contacts are mostly of the symmetrical type and occur exclusively on pallidal dendrites. No ChAT? axo-axonic synaptic modulatory action on pallidal afferents through diffuse transmission, whereas pallidal neurons may be influenced by both volumic and synaptic delivery of ACh.
- PublicationAccès libreEvidence for sprouting of dopamine and serotonin axons in the pallidum of Parkinsonian monkeys(Frontiers Research Foundation, 2018-05-15) Gagnon, Dave; Whissel, Carl; Di Paolo, Thérèse; Parent, Martin; Eid, Lara; Parent, André; Coudé, DymkaThis light and electron microscopie immunohistochemical quantitative study aimed at determining the state of the dopamine (DA) and serotonin (5-HT) innervations of the internal (GPi) and external (GPe) segments of the pallidum in cynomolgus monkeys (Macaca fascicularis) rendered parkinsonian by systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In contrast to the prominent DA denervation of striatum, the GPi in MPTP monkeys was found to be markedly enriched in DA (TH+) axon varicosities. The posterior sensorimotor region of this major output structure of the basal ganglia was about 8 times more intensely innervated in MPTP monkeys (0.71 ± 0.08 × 106 TH+ axon varicosities/mm3) than in controls (0.09 ± 0.01 × 106). MPTP intoxication also induced a two-fold increase in the density of 5-HT (SERT+) axon varicosities in both GPe and GPi. This augmentation was particularly pronounced anteriorly in the so-called associative and limbic pallidal territories. The total length of the labeled pallidal axons was also significantly increased in MPTP monkeys compared to controls, but the number of DA and 5-HT axon varicosities per axon length unit remained the same in the two groups, indicating that the DA and 5-HT pallidal hyperinnervations seen in MPTP monkeys result from axon sprouting rather than from the appearance of newly formed axon varicosities on non-growing axons. At the ultrastructural level, pallidal TH+ and SERT+ axons were morphologically similar in MPTP and controls, and their synaptic incidence was very low suggesting a volumic mode of transmission. Altogether, our data reveal a significant sprouting of DA and 5-HT pallidal afferents in parkinsonian monkeys, the functional significance of which remains to be determined. We suggest that the marked DA hyperinnervation of the GPi represents a neuroadaptive change designed to normalize pallidal firing patterns associated with the delayed appearance of motor symptoms, whereas the 5-HT hyperinnervation might be involved in the early expression of non-motor symptoms in Parkinson's disease.
- PublicationRestreintQuantitative and ultrastructural study of serotonin innervation of the globus pallidus in squirrel monkeys(Wiley, 2013-02-25) Champigny, Marie-France; Parent, Martin; Eid, Lara; Parent, AndréThe present immunohistochemical study was aimed at characterizing the serotonin (5‐HT) innervation of the internal (GPi) and external (GPe) pallidal segments in the squirrel monkey (Saimiri sciureus) with an antibody against the 5‐HT transporter (SERT). At the light microscopic level, unbiased counts of SERT+ axon varicosities showed that the density of innervation is similar in the GPi (0.57 ± 0.03 × 106 varicosities/mm3 of tissue) and the GPe (0.60 ± 0.04 × 106), with the anterior half of both segments being more densely innervated than the posterior half. Dorsoventral and mediolateral decreasing gradients of SERT varicosities occur in both pallidal segments, but are statistically significant only in the GPi. The neuronal density being significantly greater in the GPe (3.41 ± 0.23 × 103 neurons/mm3) than in the GPi (2.90 ± 0.11 × 103), the number of 5‐HT axon varicosities per pallidal neuron was found to be superior in the GPi (201 ± 27) than in the GPe (156 ± 26). At the electron microscopic level, SERT+ axon varicosities are comparable in size and vesicular content in GPi and GPe, where they establish mainly asynaptic contacts with unlabeled profiles. Less than 25% of SERT+ varicosities display a synaptic specialization, which is of the symmetrical or asymmetrical type and occurs exclusively on pallidal dendrites. No SERT+ axo‐axonic synapses are present, suggesting that 5‐HT exerts its well‐established modulatory action upon various pallidal afferents mainly through diffuse transmission, whereas its direct control of pallidal neurons results from both volumic and synaptic release of the transmitter.
- PublicationRestreintThe Primate basal ganglia connectome as revealed by single-axon tracing(Elsevier, 2015-12-01) Parent, Martin; Parent, AndréThis chapter provides an overview of the basal ganglia connectome as revealed by single-axon tracing procedures applied to nonhuman primates. These studies have shown that virtually all basal ganglia components, as well as most brainstem and thalamic nuclei with which they are reciprocally linked, harbor several distinct sets of projection neurons characteristically endowed with a highly collateralized and widely distributed axon. This morphological trait allows a complex and exquisitely precise interaction between the various basal ganglia and their related thalamic and brainstem nuclei. Our findings indicate that the basal ganglia are part of a finely tuned network that extends over several levels of the neuraxis. The anatomical elucidation of this intricate circuitry is essential to understand the complex spatiotemporal sequence of neural events that ensures the flow of cortical information through the basal ganglia, whose alteration leads to major psychomotor disabilities.
- PublicationRestreintDistribution and morphological characteristics of striatal interneurons expressing calretinin in mice : a comparison with human and nonhuman primates(2014-06-21) Beaulieu, Jean Martin; Parent, Martin; Petryszyn, Sarah; Parent, AndréStriatal interneurons display a morphological and chemical heterogeneity that has been particularly well characterized in rats, monkeys and humans. By comparison much less is known of striatal interneurons in mice, although these animals are now widely used as transgenic models of various neurodegenerative diseases. The present immunohistochemical study aimed at characterizing striatal interneurons expressing calretinin (CR) in mice compared to those in squirrel monkeys and humans. The mouse striatum contains both small (9-12 μm) and medium-sized (15-20 μm) CR+ cells. The small cells are intensely stained with a single, slightly varicose and moderately arborized process. They occur throughout the striatum (77±9 cells/mm(3)), but prevail in the area of the subventricular zone and subcallosal streak, with statistically significant anteroposterior and dorsoventral decreasing gradients. The medium-sized cells are less intensely immunoreactive and possess 2-3 long, slightly varicose and poorly branched dendrites. They are rather uniformly scattered throughout the striatum and three times more numerous (224±31 cells/mm(3)) than the smaller CR+ cells. Double immunostaining experiments with choline acetyltransferase (ChAT) as a cholinergic marker in normal and Drd1a-tdTomato/Drd2-EGFP double transgenic mice reveal that none of the small or medium-sized CR+ cells express ChAT or D1 and D2 dopamine receptors. In contrast, the striatum in human and nonhuman primates harbors small and medium-sized CR+/ChAT- cells, as well as large CR+/ChAT+ interneurons that are absent in mice. Such a difference between rodents and primates must be taken into consideration if one hopes to better understand the striatal function in normal and pathological conditions.
- PublicationRestreintThe calretinin interneurons of the striatum : comparisons between rodents and primates under normal and pathological conditions(Springer-Verlag, 2017-02-06) Parent, Martin; Petryszyn, Sarah; Parent, AndréThis paper reviews the major organizational features of calretinin interneurons in the dorsal striatum of rodents and primates, with some insights on the state of these neurons in Parkinson’s disease and Huntington’s chorea. The rat striatum harbors medium-sized calretininimmunoreactive (CR?) interneurons, whereas the mouse striatum is pervaded by medium-sized CR? interneurons together with numerous small and highly immunoreactive CR? cells. The CR interneuronal network is even more elaborated in monkey and human striatum where, in addition to the small- and medium-sized CR? interneurons, a set of large CR? interneurons occurs. The majority of these giant CR? interneurons, which are unique to the primate striatum, also display immunoreactivity for choline acetyltransferase (ChAT), a faithful marker of cholinergic neurons. The expression of CR and/or ChAT by the large striatal interneurons appears to be seriously compromised in Parkinson’s disease and Huntington’s chorea. The species differences noted above have to be considered to better understand the role of CR interneurons in striatal organization in both normal and pathological conditions.
- PublicationRestreintSingle-axon tracing study of corticostriatal projections arising from primary motor cortex in primates(Wistar Institute of Anatomy and Biology, 2006-03-14) Parent, Martin; Parent, AndréThe axonal projections arising from the forelimb area of the primary motor cortex (M1) in cynomolgus monkeys (Macaca fascicularis) were studied following microiontophoretic injections of biotinylated dextran amine under electrophysiological guidance. The microinjections were centered on layer V, and 42 anterogradely labeled corticofugal axons were reconstructed from serial frontal or sagittal sections with a camera lucida. Our investigation shows that the primate striatum receives both direct and indirect projections from M1. The direct corticostriatal projection is formed by axons that remain uniformly thin and unbranched throughout their sinuous trajectory to the ipsilateral striatum. They divide as they enter the dorsolateral sector of the post-commissural putamen, the so-called sensorimotor striatal territory. The indirect corticostriatal projection derives from a thin collateral emitted within the corona radiata by thick, long-range fibers that descend toward the brainstem. The collateral enters the putamen dorsomedially and remains unbranched until it reaches the dorsolateral sector of the putamen, where it breaks out into two to four axonal branches displaying small and equally spaced varicosities. Both direct and indirect corticostriatal axons branch moderately but occupy vast rostrocaudal striatal territories, where they appear to contact en passant several widely distributed striatal neurons. These findings reveal that, in contrast to current beliefs, the primate motor corticostriatal system is not exclusively formed by axons dedicated solely to the striatum. It also comprises collaterals from long-range corticofugal axons, which can thus provide to the striatum a copy of the neural information that is being conveyed to the brainstem and/or spinal cord.
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