1. Nervous tissue Nerve cells Glia
Ágnes Nemeskéri
2015
Semmelweis University Budapest
Department of Human Morphology and Developmental Biology

2. Neurons

3. Nerve cell Functional unit: neuron
Functional unit: neuron
- electrically excitable cell that processes and transmits information through electrochemical
signals
Cell body (often called the perikaryon)
Dendrites
-thin processes arising from the cell body - often extending for hundreds of micrometres,
branching multiple times, giving rise to a complex "dendritic tree"
Axon
- special cellular extension that arises from the perikaryon at a site called axon hillock
- travels for a distance, as far as 1 meter in humans
- there is never more than one axon

4. Ramon y Cajal – „neuron doctrine”
- theory in anatomy and physiology: the nervous system is composed of nerve cells each of which is a structural unit in contact with other units but not in continuity,
neuron is a genetic unit derived from a single embryonic neuroblast
a functional unit or unit of conduction with the nervous pathways being chains of such units
trophic unit - trophic unity of a nerve cell: axons are trophically dependent upon the perikaryal region of the same cell, and that the perikaryal region will often react to damage of its axon
polarity
Ramon y Cajal – „neuron doctrine”
Kölliker – 1867 –reticular theory
Santiago Ramón y Cajal
(1852–1934)

5. 1906 Nobel laureates ↔
Cajal
Golgi
István Apáthy
Contiguity
Continuity

6. Contiguity or continuity? Answer:

7. Basic neuron types Classification
- apolar – during embryonic, fetal development
- pseudounipolar – spinal ganglion
- bipolar – spiral ganglion – dendritic pole –
axonal pole
- multipolar – majoríty of neurons
multipolar
pseudounipolar
unipolar ?
pseudounipolar

8. Morphology of neurones
Nissl granules
Morphology of neurones
Neuronal cell body - PERIKARYON
- plasma membrane inhibiting and stimulating axosomatic synapses
- non synaptic surface: non neuronal cells of the nervous tissue:
glia cells – cellular processes
factory of neurones
Cytoplasm
- protein synthesis highly active – long processes
(1 m !!)
maintaining of cytoplasmatic membranes:
structural metabolism
- RER
- SER
- free polyribosomes
polyribosomal aggregations coupled to RER (RNA rich structure):
basophilic staining: Nissl granules (tigroid)
- present in the dendrites
- no Nissl granules in the axon
-neurofilamentum, neurotubule: perikaryon and processes
-microtubules 25-28nm
- maintaining the shape
- neurofilamentum (10 nm) – most abundant in axon
-bundles: neurofibrils
-microfilamentum: F-actin
axon hillock
Pathology
prominent deficit of neuronal soma volume in the hippocampus
high prevalence of intellectual deficits, epilepsy and the high rate of
Sudden Unexpected Death in Epilepsy in autism
reduced volume of neuronal soma is a
core pathological feature of idiopathic and syndromic autism

9. Mitochondria
distribution: over long distances - distribution to an ever-changing demand for energy
delivery of healthy mitochondria to the appropriate regions
their retention in areas with a high requirement for their Ca++-buffering capacity and energy production
able to move bidirectionally along microtubules tracts with the help of motor proteins and adaptor proteins: Milton and Miro or syntabulin
(2) Krebs cycle in the mitochondrial matrix, generating α-ketoglutarate and electron donors (NADH and succinate)
(3) Transamination of α-ketoglutarate yields the neurotransmitter glutamate, glutamate can be decarboxylated to yield GABA - another neurotransmitter
(4) electron transport chain- electron transfer is coupled with proton extrusion out of the matrix toward the intermembrane space, producing an electrochemical gradient across the inner membrane (about – 200 mV)
(5) Protons ultimately return to the matrix through the ATP synthase, using the free energy produced by the electron transfer to drive ATP synthesis
(6) calcium homeostasis, and Ca2+ ions can be sequestered in the matrix While the outer mitochondrial membrane is rather permeable to calcium, Ca2+ entry across the inner mitochondrial membrane is mediated by a uniporter, and its extrusion largely relies on a sodium/calcium exchanger.

10. Pathology of mitochondrial defect
neurological disorders characterized by a mitochondrial defect:
Alzheimer’s, Huntington’s and Parkinson’s diseases
- defects in presynaptic mitochondrial function or mitochondrial transport - display abnormalities in the synaptic vesicle cycle
- a defect in mitochondrial calcium handling capacity and/or bioenergetics
would predispose dopaminergic neurons to damage

11. Morphology of neurons Nucleus
-double layered nuclear membrane with pores
- nucleoplasm is homogenious, DNA genetic material (chromatin) is finely distributed not stained with basic dyes: in euchromatin form
prominent large nucleoli: synthesis of ribonucleic acid (RNA)
Golgi complex
- opposite to axon hillock next to the nucleus
- aggregation of flat vesicles
- protein containing vesicles budding off from the rER transported to Golgi
-proteins are modified (glycosylation, phosphorylation)
-proteins packaged into vesicles and transported to other intracellular location (nerve terminal)
Lysosome
-membrane bound vesicles
- scavenger
- ~ 50 types of acidic hydrolytic enzymes

12. Morphology of neurones
In anxiety disorders:
- fewer and shorter dendrites, less spines
Morphology of neurones
Intensive learning: more and larger spines
Dendrites
- large surface to receive signals from axon terminals of other neurons
- short processes, richly branching
-plasticity: higher synaptic activity larger dendritic tree
-same function – same spatial orientation of dendritic tree
-afferent input (excitatory or inhibitory) through axodendritic synapses
-dendritic spine increased receptive surface
-LEARNING: number of dendritic spines increases!!!!!!!!
-dendrites contain:
-ribosomes, sER, microtubules, neurofilaments, actin filament, mitochondria
-dendritic -microtubules express microtubule associated protein (MAP-2)

13. Axon
Axon hillock
Axon (neurit)
- axon hillock – conical site of origin - no Nissl granules
- first µm: initial segment nem veszi körül myelin hüvely
-action potential originates here
- axon collateral may arise near the perikaryon –recurrent collateral
- distal end of axon branches richly (telodendrion) enlarged terminal end: axon terminal –contact with other
axon, dendrit, perikaryon
- axons are myelinated or unmyelynated - node of Ranvier – action potential appears here along the axon –
- Na- and K-channels
- internodal sections: few Na-channels
-unmyelinated axon: Na-channel distribution more uniform
-axon contains:
-microtubules, neurofilaments, mitochondria, vesicles, lysosomes
-no ribosomes

14. Axonal transport Axonal microtubules
- organelles and cytoplasm - continuous movement
- vesicles bidirectional migration
Slow anterograde axonal transport
- cytoskeletal proteins, microtubules, neurofilament, myosin, actin, tubulin mm/day
Fast anterograde axonal transport
- vesicular transport: mm/day
- microtubule-dependent -2 motor proteins - ATP-ase activity
- kinesin-protein family
-synaptic transmitter propeptide containing vesicles, glycoproteins, enzymes
Fast retrograde axonal transport
- dynein dependent
- mitochondria, endosomes, lysosomes, viruses
(herpes zoster, poliovirus, rabies)
Vesicles labeled with the fluorescent dye CM-DiI are trafficking along an axon of a chick dorsal root ganglia neuron. (Upper) Fluorescent image of CM-DiI, (Middle) DIC image, (Lower) Merged image. Goshima et al, J Pharmacol Sci, 114: (2010).
Axonal transport （軸索輸送）

15. Synapse Synapse - majority: chemical synapsis
Animáció
- presynaptic transmitter release
-changes electric property of postsynaptic membrane :
-hyperpolarization or depolarization
- electric synapsis

16. GLIA

17. G protein-coupled receptors (GPCR)
Glial cell – chemical and physical isolation of neurones - to assure the neuronal functions - the half of brain is „silent” !????
GLIAL CELL CLASSIFICATION
CNS
PNS
Macroglia
astrocyte (protoplasmic, fibrous, radial)
Schwann cell
satellite cell
Microglia
mesoglia
oligodendrocyte
1997
-glia cells in the brain, spinal cord, in ganglia express
G protein-coupled receptors (GPCR)
-linked with different intracellular signaling cascades
-earlier only the neurons were believed to have these receptors
-on stimulation the intracellular Ca++ increases – excitatatory process!
-question:
what is the role of the signal mediated by GPCR ????
Ependyma
Special glia
Müller cell
Fananas glia
tanycyte

18. GLIA CELLS CLASSIFICATION 2008
1. Schwann cells and oligodendroglia cells
- produce myelin sheath in the PNS and CNS
2. Microglia
- immun cells, reactive in inflammatory processes
3. nerve/glial antigen 2 (NG2) positive glia
- oligodendroglia and astrocytes precursor cells (stem cell)
- also in adult brain
4. Astrocytes
- number, cell mass, cell surface - dominant type
- several subtypes - morphology and biochemical properties
- Bergmann glia in cerebellum, Müller glia in retina
- in a given region same morphology, immuncitochemical similarity
BUT: astrocytes may display different expression profiles of GPCR and in responses to their avtivation
- diversity is also characteristic feature of glial cells!

19. Astrocyte Protoplasmic astrocyte Fibrous astrocyte
- most numerous astrocyte
- individual astrocytes do not overlap, interdigitate
- astrocyte processes establish gap junctions
- dye to an astrocyte: hundreds of astrocytes stain – dye migrate through gap junctions
- behaves as syntitium
- processes of one astrocyte may cover synapses
- 99% of cerebrovascular surface covered by astrocyte processes
Astrocyte
Fibrous astrocyte
- mainly in the white matter
- intermedier filament synthesis (10nm) GFAP
- end feet on the brain surface:
superficial glial limiting membrane and perivascular glial limiting membrane
BLOOD-BRAIN BARRIER
Hippocampus - pyramid cells
Astrocyte-processes cover the synapses
Protoplasmic astrocytes

20. Astrocyte G protein-coupled receptors (GPCR)
-neurotransmitters activate
Stimulation: intracellular Ca++
GPCR-mediated Ca ++-dependent neuroactive substance release from astrocyte:
gliotransmitter (?)
Synapse
„tripartite synapse”

21. Glia – microglia - mesoglia
-small cells, fewer shorter processes
-ovoid nucleus
-bone marrow origin – mononuclear phagocyte family
-reactive microglial cells phagocyte

22. Oligodendroglia Oligodendroglia -small rounded cell body
-few thin processes, branching
-end of processes widen, then one process rolls around an axon
– myelin sheath in the CNS

23. Ependyma
Ependyma
-central canal of spinal cord and the walls of cerebral ventricles
- lined by cuboidal-columnar cells
- kinocilia (16 motile cilia), microvilli
- tanycytes are monociliated
in intracranial pressure Aquaporin 4 could participate
in adjustements: enhancing interstitial fluid reabsorption into brain capillaries
Functions
- beating of cilia is important for propelling CSF
- N+E-cadherin in cell junctions of multiciliated ependymal cells- natural barriers between the CSF and brain- integrity of cell layer
- adherens junctions and gap junctions
- water transport – water channel: aquaporins) and ion transport
- CSF production – choroid plexus ependyme

24. Functional importance of neuroglia
„From passive glue to excitable cells…”
Support, isolation of neuronal groups
Trophic function
Electric isolation
Regulating the molecular composition of the extracellular space
Transmitter store
Elimination of damaged neurons
Guidance of migrating neuoblasts during the ontogenesis (radial glial scaffold)
Protection of neural tissue from bloodborn chemical substances (blood-brain-barrier)
Astrocytes participate actively at the information processing of the brain (!?)

25. Pathology Microglia Reactive microglial cells
Creuztfeldt Jakob disease
HIV-infection – microglia
Reactive microglial cells

26. References
REVIEW ARTICLE
Front. Synaptic Neurosci., 22 September 2010 | 
Synaptic mitochondria in synaptic transmission and organization of vesicle pools in health and disease
Melissa Vos1,2, Elsa Lauwers1,2 and Patrik Verstreken

27. Nerve cell = neuron Continuity or contiguity between nerve cells?
Camillo Golgi
1843 – 1926.
Cajal investigated the individual nerve cells using Golgi’s technique
Golgi’s method: Golgi's staining is achieved by
impregnating fixed nervous tissue with potassium
dichromate and silver nitrate
this method stains only few cells at random, but the whole arborization
resulting reaction between potassium dichromate and silver nitrate caused deposits of silver chromate to form on the cell membrane, staining it black
Santiago Ramon y Cajal illustration: pigeon cerebellum

28. Morphology of neurons 1. Soma(cell body, perikaryon) 2. Processes
- great variability in size and shape
- diameter: µm
- contains the nucleus
2. Processes
- branching cytoplasmic processes
- cell body of a neuron frequently gives rise
to multiple dendrites
- there is never more than one axon,
although the axon may branch hundreds of times
before it terminates