Cytology Nikon © DENT/OBHS 131 Neuroscience

reticular theory 1886: Golgi-techniques 1888: Ramon y Cajal 1897: Sherrington Building blocks

Learning Objectives Compare and contrast the morphology & function of neurons and glial cells Explain neuronal polarization in terms of information signaling Be able to give reasons for the energetic demands of neurons Discuss the different roles of different categories of glial cells Describe the relationship of neurons and glia with respect to synaptic signaling and action potential propagation

What are the most important types of cells in the brain? 1.Neurons 2.Glia 3.Neither neurons nor glia 4.Other cells

Types of cell Neurons - nerve cells 100 billion Glial cells ≈ 10 X neurons 50:50 volume CNS vs PNS autonomic (week 10) motor & sensory (weeks 5-8)

Learning Objective #2 Explain neuronal polarization in terms of information signaling

Basic function of a neuron Transmit information from here to there

Parts of a neuron Dendrites receive information Soma synthesize stuff electrical integration Axon information conduction Axon terminal transmit information

En masse Segregation white gray Gross lab (week 2)

Same but different Multipolar (typical) single axon multiple dendrites Bipolar Pseudo-unipolar

What type of cell is the large neuron? 1.Purkinje 2.Pyramidal 3.Granule 4.Motor 10

Pseudounipolar neurons…. single axon - bifurcates classical example - sensory fibers

Classes of neurons Sensory Motor Interneurons Projection somatosensory (weeks 5-6) sensory-motor integration (week 6) motor (weeks 7-8)

Synapses Dendritic shafts / spines inhibitory / excitatory (weeks 3-4) synaptotagmin MAP2

Axons are long ≈ 5ft motor neuron (e.g. Sciatic nerve) ≈99% cytoplasm How to accomplish fast signaling (week 3)? How to maintain structure? How to communicate between distant parts?

Cytoskeleton axon growth cone (Ken Balazovich)

Cross section of dendrite Neurofilaments filamentous actin Microtubules Tubulin (10% brain protein) substrate for axonal transport MAPs e.g. Tau (weeks 10-11)

Active transport Slow: few mm / day Fast < 400 mm /day Retro Antero kinesindynein molecular motors

Ribosomes: Nissl substance In dendrites (not largely in axons) may offset long transport distances in axons Local protein synthesis at the base of spines - plasticity (weeks 10-11)

Leaching Objective #3 Be able to give reasons for the energetic demands of neurons

High energy use % total energy consumption at rest Maintain ionic gradients (ion-exchange pumps) Protein synthesis Axonal transport Mitochondria Site of oxidative metabolism - ATP Brain exclusively dependent on glucose Found throughout the perikaryon, dendrites, spines, axons and in synaptic terminals

Other organelles Similar to other cells Nucleus: only a few 1000 CNS specific genes - encode CNS proteins extensive RNA splicing Golgi: post-translational modification

Relationship to other cells

Brain Glue

Special properties of glia? Compared to neurons: (Astrocytes) star-shaped & largely lack polarity No synapses - cells communicate through gap- junctions Relatively low energy requirement; function well under anaerobic conditions phalloidin tubulin DAPI

Learning Objective #4 Discuss the different roles of different categories of glial cells

Key roles of glia Remove glutamate and other amino-acids from extracellular space: de-toxify the brain Form myelin to insulate axons Serve numerous homeostatic functions Can and do proliferate postnatally

Classification Radial glia - development (next session) Astrocyte protoplasmic astrocyte (Type 1) fibrous astrocyte (Type 2) Schwann cell Oligodendrocyte Macroglia Microglia

Microglia engulfing a dying oligodendrocyte: phagocytotic cells in the nervous system blood derived cells comparable to macrophages remove debris from the brain following injury and constitute an important defense system against pathogens.

Radial glia Development (week 1) neuronal guidance

Learning Objective #5 Describe the relationship of neurons and glia with respect to synaptic signaling and action potential propagation

Schwann cell Myelination in the PNS

Myelin sheet One-to-one

Gap junctions and disease Charcot-Marie-Tooth disease progressive loss of PNS axons - weakness, atrophy

Nodes of Ranvier fast AP propagation (week 3)

Oligodendrocytes

1:10 to 1:50

Unmyelinated CNS fibers

CNS vs. PNS summary

Astrocytic end feet…… contact blood vessels

Astrocytic endfoot Induce the blood-brain-barrier Active transport

From here to there…..

Buffering of extracellular ions Extracellular space is very narrow => small ionic fluxes cause large concentration changes

Astrocytes are not really star-shaped non-overlapping space-filling (Bushong et al., 2002)

Transmitter “shuttle”

Nervous system regeneration The CNS does not regenerate while the PNS does This is NOT due to differences in central and peripheral neurons but due to differences in their glia CNS oligodendrocytes actively suppress regeneration reactive gliosis PNS Schwann cells promote it

Glia versus neuron - difference? excitability (Bergles et al., 1997)