Ákos Lukáts M.D., Ph.D. (lukats.akos@med.semmelweis-univ.hu) Nervous Tissue Ákos Lukáts M.D., Ph.D. (lukats.akos@med.semmelweis-univ.hu)

Evolutional prospective Role: to detect and interpret signals from the body and its surroundings, to prepare and execute adequate response In multicellular organs there is and increasing demand for more complex regulation and communication between cell types: to systems evolve the endocrine (hormonal) and the nervous system Ectodermic origin in all species

General tendency Network-like organization in some species Three main tendencies: 1) Centralization central NS: interpretation peripheral NS: detection execution Ganglionic vs. tube-like NS (invertebrates) (vertebrates) 2) Segmentation: one center/ganglion in each segment 3) Cephalisation: dominance of cephalic centers/ganglia (brain) – difference in size, gradually taking over functions from and overriding lower centers

Neurulation 1 (Day 17-29) Neural tube: central nervous system Neural crest: peripheral nervous system, etc…

Neurulation 2 Proper administration of folic acid decreases the risk of neural closure defects!

Cell-types of NS Neurons: excitable (soldiers) action potentials synapses polarized Glia cells: supporting cells (to glue) (backup) isolation (barriers) metabolic support myelin sheath etc.

www.whonamedit.com www.nobelprize.org/medicine/articles/golgi/

Neurons morphology Classified according to the number and type of processes. Prototype: multipolar neuron. Having several, branching, smaller processes (dendrites) for receiving, and one longer process (axon) to pass the information – polarized cell! Most cell organelles are located around the nucleus in the perikaryon. Polarization – the impulse pass from dendrites through pericarion to the axon and telodendria. The parts are electrically different. Action potentials can only develop at the axon hillock and axon. Synapses pass the impulse to adjacent cells.

Pseudounipolar

Neurons and polarization dendrite perikarion axon hillock (AP) axon synapse motoneurons, pyramidal cells etc. most sensory neurons Most common in invertebrates acoustic and vestibular system

Multipolar neurons Cerebral cortex: pyramidal cells impregnation Spinal cord: motorneurons Golgi impregnation

Spinal cord: motorneurons Luxor fast blue Bipolar neurons acoustic system, toluidin blue

Cerebellum: Purkinje cells immune staining

Excitability: resting membrane potential 1 Unequal distribution of charged molecules. Abundant Na+ and Cl- .in extracellular, higher concentrations of proteins and K+ in intracellular space. Maintained both by passive and active mechanisms -Na-K-ATP-ase is the most important pump, consuming 70% of resting energy in an average neuron! Na+:135-145 mmol/L Na+: 15 mmol/l + Cl-: 9 mmol/l Proteins - K+: 150 mmol/l Cl-: 125 mmol/l K+: 3.5-5.5 mmol/l A Na-K-ATP-ase EC. IC. Proteins - 3Na+ 70-90 mV transmembrane potential difference in most neurons 2K+ ATP ADP+P

Excitability: resting membrane potential 2 Two force acts on every charged particle around or in the cell. An electric force due to the potential difference and a chemical force, due to the different concentrations. The sum of these two forces drive the ion, if the membrane becomes permeable to it. The potential, when the two forces add up to zero, is called equilibrium potential. At resting membrane potential: The greatest force acts on Na+ ions. K+ is almost in equilibrium. Na+:135-145 mmol/L Na+: 15 mmol/l - + Cl-: 9 mmol/l Proteins - K+: 150 mmol/l Cl-: 125 mmol/l K+: 3.5-5.5 mmol/l Proteins - At resting stage the cell membrane is practically impermeable to most ions.

Excitability: local response vs. action potential

Local response

Action potential 1 Na+ channels are closed, K+ channels open, to allow K+ influx, causing repolarization. Voltage gated Na+ channels open, Na+ moves into the cell, which depolarize. These channels close quickly. Na-K-ATP-ase restores resting membrane potential and ion balance. Alan Hodgkin and Andrew Huxley, action potential: 1963 Nobel-prize John Carew Eccles, synapse: 1963 Nobel-prize http://www.science.smith.edu/departments/NeuroSci/courses/bio330/squid.html

Action potential 2

Summary An action potential will develop if the depolarization has reached the threshold and the cell membrane contains voltage gated Na+ channels (axon). The local response decreases in altitude, tha action potential is constant in shape, and spreads without change (all or nothing). The continuous depolarization/repolarization at an action potential is quite energy demanding, and relatively slow process. The local response is energetically more favorable and spreads quicker, but its amplitude decreases quickly, unable to be transported over longer distances (perikaryon, dendrites).

Conduction in the axon Saltatory conduction. The myelin sheath isolates the axon from extracellular space. Action potential can only develop at the naked points (nodes of Ranveir), in between them, the impulse travels with electrical conduction (local response). The myelin is produced by glial cells, Schwann cells in the periphery, oligodendrocytes in CNS.

Myelin sheath Schwann cells Oligodendrocyte

Conduction speed Conduction speed is determined by: diameter of the axon thickness of myelin Different types of fibers have different conduction speeds

Synapse

Chemical synapse AP reaches presynaptic terminal Ca++ enters the cell Synaptic vesicles fuse with the membrane Transmitter is released to synaptic cleft Transmitter binds to its receptor Response of postsynaptic cell (depolarization or hyperpolrization)

Electric synapse Gap-junctions between two adjacent cells: small ions can pass freely between them.

Not only present in neural tissue (cardiac muscle and its conduction system, smooth muscles; everywhere when coordinated cell actions are necessary). Quick conduction, small ions (Ca++) can pass freely. No synaptic delay. Bidirectional connection! Less precise regulation, but could be opened and closed Also present between glia cells – indispensible for metabolic support.

Glia cells Astrocytes: Star shaped cells in CNS, making limiting membranes, taking part in forming blood-brain barrier, and metabolically supporting the neurons. Connected with each other via gap junctions.

Myelin sheath Schwann cells Oligodendrocyte

Basic unit of action: reflexes

Literature Szentagothai J, Réthelyi M: Funkcionális anatómia, Medicina, 1989 Sobota - Atlas of Human Anatomy, 20th edition, Urban and Schwarzenberger, 1993 http://faculty.washington.edu/chudler/facts.html Carola R, Harley JP, Noback CR: Human Anatomy and Physiology, McGraw-Hill Imc, 1990 Greenstein B: Color Atlas of Neuroscience, Thieme, 2000 NEUROSCIENCE: Third Edition, Sinauer Associates, Inc, 2004 A szövettani felvételek a Humánmorfológiai Intézet anyagából származnak.