Motorische Bahnsysteme Csillag András Semmelweis Egyetem, Budapest

Klassifikation der absteigenden motorischen Faserbahnen I Klassische Aufteilung: willkürlich, zielorientiert (Pyramidenbahn) tractus corticospinalis tractus corticonuclearis (corticobulbaris) automatisch, stereotypisch (extrapyramidale Bahnen) tractus reticulospinalis, vestibulospinalis, rubrospinalis, olivospinalis, tectospinalis

Klassifikation der absteigenden motorischen Faserbahnen II Moderne Aufteilung: mediales absteigendes System tractus vestibulospinalis, tractus reticulospinalis laterales absteigendes System tractus corticospinalis tractus rubrospinalis Körperhaltung (Rumpf), Kopf- und Blickstabilisierung Prinzipale Afferenzen: optisch, vestibular, propriozeptiv, Kleinhirn- willkürliche, organisierte Bewegungen am Gesicht und an den Extremitäten Prinzipale Afferenzen: somatosensibel, kortikal, Basalganglien, Kleinhirn

Funktionelle Gliederung der motorischen Bahnen

Wichtige absteigende motorische Bahnen

Tractus vestibulospinalis

Tractus rubrospinalis und Tractus reticulospinalis

Schematische Darstellung der Basalganglien GP – globus pallidus (GPe) STN – nucl. subhalamicus SNc – substantia nigra p. compacta SNr – substantia nigra p. reticulata EP – nucl. entopeduncularis (GPi) SC – colliculus superior RF – formatio reticularis Simplified block diagram of the circuitry of the basal ganglia. Inhibitory projections are shown by mottled lines, excitatory projections by dotted lines. Cortical information that reaches the striatum is conveyed to the basal ganglia output structures (SNr}EP, substantia nigra pars reticulata}entopeduncular nucleus) via 2 pathways, a direct inhibitory projection from the striatum to SNr}EP and an indirect pathway, which involves an inhibitory projection from the striatum to globus pallidus (GP), an inhibitory projection from the GP to the subthalamic nucleus (STN) and to the output nuclei and an excitatory projection from the STN to SNr}EP. The information is then transmitted back to the cerebral cortex via the thalamus or conveyed to various brainstem structures including the superior colliculus (SC) and the parvicellular reticular formation (RF). Dopaminergic neurons of the SNc provide a massive feedback projection to the striatum (hatched line) and modulate the flow of cortical information. A proportion of GP neurons also feedback to the striatum where they innervate interneurons which also receive cortical input. Cortical information can also reach the basal ganglia via the corticosubthalamic projection. J. P. Bolam et al. J. Anat. (2000) 196, pp. 527±542,

Lokomotorische Steuerungskreise der Basalganglien normaler Zustand pathologischer Zustand (Parkinsonismus)

Prefrontale – subkortikale Kreise anterior cingulate cortex dorsolateral prefrontal cortex orbitofrontal lateral cortex impairments: poor card tests, reduced flexibility of learning, lack of constructivity impairments: impulsive behaviour, recklessness impairments: reduced attention, memory deficit, affective disorders

Typisches Neuron im Striatum: medium spiny neuron

Synaptische Organisation vom Striatum I kortikale und tegmentale (dopaminerge) Axonendigungen konvergieren an einem dendritischen Dorn Kortikaler Axon (ctx), Biocytin-markiert (anterograder Transport), Tyrosinhydroxilase (TH) markiert einen dopaminergen Neurit medium spiny neuron Golgi-impregniertes Präparat aus dem Striatum der Ratte J. P. Bolam et al. J. Anat. (2000) 196, pp. 527±542,

DARPP-32: central regulator and integrator of glutamatergic and dopaminergic neural mechanisms

Multisite phosphorylation of DARPP-32 Blue arrows – positive effect Red arrows – negative effect Svenningsson et al. Annu.Rev.Pharmacol. Toxicol. 2004, 44, 269

Signaling pathways mediating the effect of neurotransmitters and drugs on DARPP-32 phosphorylation at Thr34 in a typical striatal projection neuron Neural pathways interconnecting different subnuclei of the basal ganglia Blue – excitatory pathways; Red – inhibitory pathways; Dark green – modulatory dopamine pathways; Light green - modulatory serotonin pathways Svenningsson et al. Annu.Rev.Pharmacol. Toxicol. 2004, 44, 269

Integration mechanisms involved in dopamine and glutamate signaling via kinase/phosphate cascades Shaded area – the PKA/PP-2A/Thr75-DARPP-32/PKA/Thr34-DARPP-32 cascade Blue arrows – prodopaminergic steps Red arrows – antidopaminergic steps of regulation Svenningsson et al. Annu.Rev.Pharmacol. Toxicol. 2004, 44, 269

Glu+ terminals synapse with DARPP-32+ dendrites in MSt Glu+ axon terminal synapsing with a DARPP-32 containing dendrite in MSt Glu- axon terminal synapsing with a DARPP-32 containing dendrite in MSt Csillag et al., Brain Res Bull 76 (2008) 183-191

Glu+ terminals synapse with DARPP-32 negative dendrites in MSt Glu+ axon terminals synapsing with unlabelled dendrites in MSt Csillag et al., Brain Res Bull 76 (2008) 183-191

Somatotopie der motorischen Hirnrinde

Tractus corticospinalis Ablauf und Endigungen im Rückenmark ACSP – anterior (uncrossed) corticospinal tract LCSP – lateral (crossed) corticospinal tract

Prämotorische Steuerneurone (LOPI) sowie motorische Einheiten im Rückenmark

Mustergenerierende Neurone des Rückenmarks (Central Pattern Generators, CPG) Rhythmusgenerierende innere Zone Mustergenerierende äussere Zone Postulated organization of locomotor central pattern generator (CPG). V2a, Hb9, and LC dI6 interneurons are postulated to comprise the rhythm-generating core of the locomotor CPG and receive descending input from brain stem centers known to initiate rhythmic locomotor activity in the spinal cord. We propose that these cells provide input onto the pattern-forming layer that includes dI3, V2a, V0, Hb9 and TC dI6 cells. Members of the pattern-forming layer make direct connections onto motoneurons (MN). Documented synaptic connectivity indicated by solid lines, proposed synaptic connectivity by dashed lines. Inhibitory terminal indicated by black ball, excitatory terminal by open triangle. Hemmende Synapse MN – Motoneuron im Vorderhorn dI3 – V2a – genetisch determinierte Typen von Interneurone Erregende Synapse Jason Dyck, Guillermo M. Lanuza, and Simon Gosgnach, J Neurophysiol 107: 3256 –3266, 2012. nyomán

Last Order Premotor Interneurons (LOPI) iLOPI - ipsilaterales prämotorisches Interneuron (Schaltneuron) cLOPI – kontralaterales prämotorisches Interneuron (Schaltneuron) Birinyi A. Habilitációs Tézisek, 2015

Kommissurale Interneurone des Rückenmarks iCIN – ipsilaterales kommissurales Interneuron cCIN – kontralaterales kommissurales Interneuron MN - Motoneuron Birinyi A. Habilitációs Tézisek, 2015

Rückwärtshemmung (rekurrente Hemmung) des Motoneurons durch Renshaw-Zellen http://www.learnneurosurgery.com/

Schaltplan der Interneurone im Rückenmark Vorwärtshemmung feed-forward inhibition Rückwärtshemmung (rekurrente Hemmung) Feedback (recurrent) inhibition Hemmendes Interneuron vom Typ Ia Hemmendes Interneuron vom Renshaw Typ http://www.twitter.com/TheGaitGuys

Bahnsysteme des Rückenmarks Absteigende, motorische Efferenzen Aufsteigende sensible Afferenzen

Faserordnung der Capsula interna inkl. Pyramidenbahn CA – crus anterius G – genu (‘Knie’) CP – crus posterius G – Kopf, Gesicht A – obere Extremität B – untere Extremität