1. Cell Biology of Neurons
Sept 8, 2006

2. The nervous system is composed of billions of processing units (neurons) whose cellular processes (the dendrites and axons) form an elaborate and complex meshwork of circuits and pathways. Signals are transmitted between neurons via specialized cell-cell contacts known as synapses.

3. Neurons are highly compartmentalized cells

4. Neurons are highly compartmentalized cells

5. Neurons are highly compartmentalized cells

6. Neuronal form is highly variable

7. The Neuronal Cell Body

8. Neuronal cell bodies:. -typical assortment of organelles
Neuronal cell bodies: -typical assortment of organelles -point of origin for processes -transcriptional powerhouses -provide virtually all of the protein constituents for the entire cell
100 µm
toe
6 feet

9. Nucleus
Rough endoplasmic
reticulum
Plasma membrane
Smooth endoplasmic
reticulum
Lysosome
Peroxisome
Cytosol
Mitochondrion
Golgi complex
Ribosomes

10. The plasma membrane bounds the cell, separating the ECF from the ICF.
It controls the passage of substances into and out of the cell.
The nucleus contains DNA and specialized proteins enclosed by a double-layered membrane.
DNA codes for the synthesis of structural and enzymatic proteins, and is the blueprint for cell replication.

11. The cytoplasm consists of the organelles and the cytosol.
Organelles are separate, membrane-bound compartments. Organelles include the:
endoplasmic reticulum
Golgi complex
lysosome
peroxisome
mitochondrion
The cytosol is a semiliquid, gel-like mass.

12. The sER packages new proteins in transport vesicles.
ER lumen
Rough ER
Smooth ER
The rER is an extensive, continuous membranous network of fluid-filled tubules and flattened sacs that is partially covered with ribosomes. rER synthesizes proteins for secretion and membrane construction.
The sER packages new proteins in transport vesicles.
Ribosomes

13. The Golgi complex packages vesicles and targets them to the appropriate cellular destination.
Set of stacked, flattened membranous sacs. It modifies, packages, and distributes products.

14. Peroxisomes and Lysosomes
Peroxisomes house oxidative enzymes that detoxify various waste products.
Lysosomes serve as the intracellular digestive system. They are membranous sacs containing hydrolytic enzymes that destroy foreign substances and cellular debris.

15. Mitochondria are the energy organelles
Mitochondria are the energy organelles. They are enclosed by a double membrane. The inner membrane is folded into cristae.
Mitochondria are the major site of ATP production. They contain enzymes for the citric acid cycle (matrix) and the electron transport chain (inner membrane cristae).

16. The Cytosol functions for intermediary metabolism, protein synthesis, and nutrient storage.
Enzymes in the cytosol regulate degradation, synthesis and transformation of small organic molecules (simple sugars, amino acids, fatty acids), capturing energy for cellular activities and raw materials for maintenance of cellular structure, function and growth.
Ribosomes (free in the cytosol) are the site of protein synthesis.
Glycogen and fat are stored in the cytosol (inclusion bodies).

18. The axon hillock and initial segment

19. The Myelin Sheath

20. The Axon

21. Axonal arborizations can be quite complex

22. The Synapse

23. Symmetric and asymmetric synapsessp
Dend
Symmetric and asymmetric synapses

24. Dynamic Polarization
Axo-dendritic
Axo-somatic

25. Dynamic Polarization: Exceptions
Spinal cord
afferent terminals contacted by interneurons-
“pre-synaptic inhibition”
Axo-axonic

26. Dynamic Polarization: Exceptions
Olfactory bulb and retina
Dendro-dendritic
Dendro-somatic

27. Dendritic arbors: complex geometries

28. The Dendrite
T.E.M.
Freeze fracture sp

29. Polyribosomes are sometimes associated with dendritic spines

30. Spine morphology is affected by synaptic activity

31. The Cytoskeleton (Intermediate filaments)
Abnormalities associated with degenerative diseases - Alzheimers, Down’s, ALS, etc.
Intracellular “rapid” transport - severely disrupted by Colchicine (depolymerize microtubules

32. The Cytoskeleton is a complex protein network in the cytosol.
The cytoskeleton functions as an integrated whole and links other parts of the cell together.
Its three types of elements are microtubules, microfilaments, and intermediate filaments.
neurofilaments

33. Axoplasmic transport
Dendrites have limited capabilities for local protein synthesis,
but axons have essentially none
Thus, both types of processes require transport of proteins
produced in the cell body
Multiple transport systems, transport different types of material
to different intracellular compartments, at different rates

34. Endoplasmic
reticulum
Nucleus
Golgi
complex
Secretory
vesicle
Microtubular “highway”
Axon
Debris
Axon
terminal
Lysosome
Cell body

35. Neurocytology & Tract-tracing
Widely used techniques for studying neurons and circuits:
Visualization of neurons Nissl staining, Golgi methods, intracellular dye injections, immunohistochemistry
Degeneration and reactive changes in the neuron after lesion
Wallerian degeneration
Axonal transport methods
Autoradiography, HRP, Lectins, Biocytin, Dextrans, Fluorescent Tracers

36. Neuronal cell bodies: Nissl method

37. The Golgi method
cerebellar
Purkinje cell

38. Intracellular injection of Lucifer Yellow
Biolistics (“gene-gun”)
Intracellular injection of Lucifer Yellow

39. Immunohistochemistry
L7 protein reveals cerebellar
Purkinje cells
PEP-19 antiserum reveals the
calyx of Held

40. Tract-Tracing Anterograde Degeneration: Reduced silver method and
Anterograde Wallerian
degeneration
Retrograde
Anterograde
Degeneration:
Reduced silver
method
and
electron microscopy

41. Anterograde Tract-tracing
Autoradiography
Collateral
projections
Labeled
terminals
Anterograde
transport
Uptake by
Cell body
Radioactively labeled amino acid

42. Retrograde Tract-Tracing
HRP, Dextran
Retrograde
transport
Uptake by terminals
HRP

43. Tract-tracing: Fluorescent tracers
Superior
olivary
neuron

44. Combining techniques at the LM and EM level