Mark Kozsurek, M.D., Ph.D. mark@kozsurek.hu

1. Microscopical structure of the spinal cord, Rexed zones. Receptors and effectors, spinal reflexes,proprioceptive reflex arc. http://siennaartstudios.com/shop/thermal-dols-spinal-cord-nociceptors Mark Kozsurek, M.D., Ph.D. mark@kozsurek.hu EM II 9-17, 24 Sept, 2019

2. INPUT:sensoryfibres OUTPUT: motor fibres Terms:white and graymatter, spinalnerve, dorsal and ventralroots, spinalnerves, spinalganglion (dorsalrootganglion - DRG)

3. 1. Wheredoestheinformationcomefrom? RECEPTORS • ancient - free nerveendings • invadetheepithelium of theskin and mucosa, occure in thewalls of viscera • no highlyspecializedstructuresaroundtheperipheralprocesses of sensoryneurons • pain and temperature, withrelativelyhighthreshold • relativelynew - specializedstructures • rather in thedermis and subcutis, in joints, muscles and tendons • complexstructuresaroundtheperipheralnerveendingscomposed of differentcelltypesincludingmodifiedSchwann-cells • lowthresholdfortouch, pressure, vibration, stretch

6. Meissner’s corpuscle Lamellar structure formed by modified Schwann cells around nerve endings. Are found in the conn. tissue papillae of the skin.

7. (Vater-) Pacinian corpuscle Concentrically arranged layers of modified Schwann cells around nerve endings. Are found in dermis or even deeper in the subcutis. (Can not only occur in the skin but also in the pancreas!)

8. Muscle spindle

9. 2. Howdoestheinformationreachthespinalcord? NERVE FIBRES Please note, that even the unmyelinated axons are supported by Schwann cells but in a different way!

10. C-fibres unmyelinated, Aδ-fibres thinmyelinsheath Aα, Aβ-fibres thickmyelinsheath, sensoryganglionwithpseudounipolarneurons )

11. 3. Whathappens in thespinalcord? Information is processed, decision is made and commandsaresenttotheeffectors. viscerosensory visceromotor somatosensory somatomotor skeletalmuscles skin, muscles, joints, tendons internalorgans smoothmuscles, glands brain spinalcord

12. 3. Whathappens in thespinalcord? Information is processed, decision is made and commandsaresenttotheeffectors. viscerosensory visceromotor somatosensory somatomotor v skeletalmuscles skin, muscles, joints, tendons internalorgans smoothmuscles, glands brain spinalcord SENSORY GGL. AUTONOMIC GGL.

13. EFFECTORS (muscles and glands) CNS directly controls skeletal and visceral striated muscles through the neuromuscular junctions: there is no need for synapses on the periphery.

14. Axons of autonomic neurons of the CNS terminate in autonomic ganglia and only the axons of those neurons resting in them will reach the target organs. Without at least one synapse on the periphery CNS has no direct influence on smooth muscles and glands.

15. 4. Howdotheneuronalnetworks of thespinalcordcontributeto decision making? Laminarorganization of thespinalcord (Rexed, 1952) : especially in thedorsalspinalhorn, lamina I -VI

16. Dorsalhorn lamina II: substantiagelatinosa Rolandi

18. High-threshold, slow-conducting, thin-myelinated Aδ and unmyelinated C fibresconveypredominantlynociceptiveinformation (pain, heat) tothelamina I-III. Low-threshold, high-conducting, thick-myelinated Aβfibrescarrynon-painfullstimuli and terminateindeeperlaminae of thespinaldorsalhorn. • Dorsalspinalhornplays a crutialroleinsensoryinformationprocessing. Local circuitneuronsare more numerous, projection neuronsforwardingstimulitohigherlevels of the CNS constituteonly 5-10%. • Lamina II is denslypackedwithmu-opioidreceptorsbindingmorphine and otheropioidanalgesics.

19. Intermediatesubstance IML CLARK-STILLING IMM IMM: intermediomedialnucleus, IML: intermediolateralnucleus

20. Lateralhornexistsonlyinthethoracic and upperlumbarsegments. Attheselevelsappearance of thelateralhorncan be explainedbythelateraltransposition of the IML nucleus. • IML nucleuscontainspreganglionicneurons of thesympathetic (thoraco-lumbarlevels) and parasympathetic (sacralsegments) nervoussystem, withotherwordsvisceromotorfibresarisefromthisnucleus. • IMM nucleus is consideredas an autonomicspinal reflex centre. • Dorsalorthoracicnucleus (of Clarke-Stilling) foundinthe Th9-L3 segments is thesource of thedorsalspinocerebellartract (ofFlechsig). Downwardcontinuation of thisnucleusin L4-S3 segments is theapproximate site of originoftheventralspinocerebellartract (ofGowers). Both of thesetractsconvayproprioceptivinformationtothecerebellum.

21. Ventralhorn

22. Recurrent inhibition: alpha-motoneurons have an axon collateral that terminates on the Renshaw-neuron inhibiting the alpha-motoneuron from which the recurrent collateral arised.

23. A typical neuron in the microscope: prominent nucleolus in the large, oval or rounded, poorly stained nucleus, surrounded by dark, basofilic, granulated cytoplasm, which is always darker then the nucleus.

24. Spinal reflexes • Reflex: involuntary and automaticresponseto a stimulus • A (1) receptoris responsiblefordetecting a stimulus and converting itinto a neuronalsignal. Evokedactionpotentialsreachthecentralnervoussystemthroughthe(2) afferentlimb. Decision is made and response is generatedbythe(3) centralprocessingneuronalnetworks. (4) Efferentlimbexitsthecentralnervoussystem and terminatesonthe(5) effector, whichmight be a muscleor a gland. (1) to (5) componentsaltogetherconstitutethe reflex arc! • In thecase of spinal reflex arcsthestimulus is received and processedbythespinalcord and theresponse is organized and performedbythespinalneuronalcircuits. Undernormalcircumstancesstimulievokingspinal reflexes alsoreachthebrain and descendingfibresfromhighercentresmaymodulatespinal reflexes butexperimentallyspinal reflexes can be evokedevenaftertheremoval of thebrain!

25. Proprioceptive reflex arc • Synonyms:stretch reflex, monosynapticspinal reflex, myotatic reflex • Stretching a muscleresults in itscontractionprovidingautomaticregulation of skeletalmusclelength and theposture of the body. The „stretchreceptors” arethemusclespindles.

26. MUSCLE SPINDLE alpha-motoneuron gamma-motoneuron flower-spray anulospiral terminals

27. Muscle spindles are special stretch receptors enclosed by a connective tissue capsule. Within the capsule the intrafusal fibres are present, while outside the extrinsic muscle fibres of the host muscle can be found. Intrafusal fibres are innervated by gamma-motoneurons and extrafusal fibres receive stimuli from alpha-motoneurons. • Within the muscle spindle two types of sensory terminals, the anulospiral endings and the flower-spray terminals can be distinguished. These inform the CNS about the actual length and movement of the muscles.

29. Muscle spindle → spinal ganglion → dorsal root → alpha-motoneuron in the ventral horn → peripheral nerve → skeletal muscle fibres surrounding the muscle spindle. Collaterals through inhibitory interneurons will avoid simultaneous contraction of the antagonist muscle groups.

30. Objectheld in handsstretchestheflexors of thearm and duetotheproprioceptive reflex arc theflexorswillcontract and hold theweight. Kneejointstendtoflexundertheweight of the body, butstretching of thequadricepsfemorismuscleactivatestheproprioceptive reflex whichincreasesthetone of theextensorsavoidingthecollapse of the human body. Proprioceptive spinal reflex developed in response to gravity.

31. Gamma-loop descending pathways adjustingthethreshold of musclespindles gamma motoneuron alpha motoneuron

32. Golgi tendonorgan

33. Both the gamma-loop and theGTOscontributetotheregulation of motor functionsatspinallevel. • Gamma-loopsetsthethreshold of musclespindles: theshorterthespindlethe more sensitivetostretching. • In GTOsaxonsamongcollagenbundlescan be activatedbytransformations of themusculotendinousjunction. • GTO is connected in series tothemusclefibres. • Inhibitsoverstimulation of muscles and preveventsbone, tendonorjointinjuries.

34. Thankyouforyourattention!