1. Nervous System – Cells and Their Function

• Building blocks of cognition

  
• Nucleic acids


  DNA

  RNA

  DNA codes for ~23,000 human genes
• Protein


  • ~42 million protein molecules/yeast cell
  • [from 5,858 yeast genes]
• Lipids


  • ~1,000 lipid molecules/cell
• Other molecules cells are made of

  • Polysaccharides
  • Inorganic ions (Mg, Ca, Fe)
  • Water
• Cell composition


  Key cell molecules made by each cell from

  • recycled molecules
  • derived from diet

  70% water

  30% organic/inorganic molecules

  CELL BY DRY WEIGHT:

  
• Gene expression: DNA to RNA to PROTEIN

  
• Enormous variation in how the genetic code can be interpreted

  
• What do genes and their protein products do?

  
• Different representations of DNA

  
• Difference between DNA and mRNA

  mRNA uses U instead of T, but is sometimes written without changing all the T’s to U’s and may be referred to as cDNA – complementary DNA
• Proteins: Shapes and Sizes

  
• Typical cell

  
• Organelles associated with gene expression

  Transcription:

  • Nucleus
  • Nuclear pore

  Translation

  • Ribosomes
  • RER
  • Amino acids

  
• Other important cellular organelles and structures

  
• Different types of cells in the brain

  MAJOR BRAIN CELL TYPES:
• Different types of cell in the brain: MAJOR BRAIN CELL TYPES

  • Neurons
  • Astrocytes
  • Microglia
  • Oligodendrocytes
  • Endothelial

  
• Different types of cell in the brain: MINOR BRAIN CELL TYPES

  • Smooth muscle cells
  • Pericytes
  • Vascular leptomeningeal cells
  • Ependymal cells
  • Epithelial
  • Lymphocytes
  • Schwann cells – peripheral nervous system
• Cell size + shape

  
• Brain cell types in reality are heterogeneous

  
• The location, structure & appearance of organelles can vary

  
• Neurons


  • Neuroectoderm origin
  • Neuronal Stem Cells (NSCs)
  • They are post-mitotic – Limited neurogenesis in the adult
  • Most common cell in the CNS, ~50% in brain
  • Specialise in cell-to-cell communication forming neural networks
  • Highly responsive to their environment - plasticity
  • Extremely active cells
  • Express markers: neurofilament proteins

  
• Oligodendrocytes


  • Neuroectoderm origin
  • From late gestation, from Oligodendrocyte Progenitor Cells (OPCs) or from Neuronal Stem Cells (NSCs)
  • Form myelin sheaths around axons in the CNS – required for efficient signal conductance
  • Oligodendrocytes provide crucial metabolic support to neurons
  • Express markers: NG2, Olig1, MBP, PLP and MOG

  
• Astrocytes (sometimes called glia)

  • Neuroectoderm origin, ~50% glia population
  • Regulation of synaptic connectivity
  • Maintenance of ionic/neurotransmitter homeostasis in the extracellular milieu
  • Can form gap junctions and a syncytial network of cells
  • Wound healing and limitation of inflammation
  • Guide circuit formation in development
  • Express markers: GFAP, vimentin and GLAST

  
• Microglia


  • Arise from myeloid progenitors in the blood island in the yolk sac1
  • First wave of ‘primitive haemopoiesis’ (E8.5-E9.5 in mice)
  • Similarities with other macrophages – monocytes from greek for "eater"
  • Resident inflammatory cells of the CNS, ~10-20% glia population Innate Immune System
  • Microglia respond quickly to even minor pathological insults
  • Shape neural circuits and modulate synaptic transmission in the adult brain
  • Express markers: Iba-1 (AIF), C3 complement receptor2 (CD11b/CD18 heterodimer)

  
• Brain cell types are heterogeneous – can be further classified

  Multiple brain cell subtypes

  ~100 different transcriptionally distinct cell types in brain samples e.g. microglia

  ~9 major subtypes

  • e.g. neurons
  • von Economo neurons
  • radial neurons
  • pyramidal neurons
  • fork neurons
  • Place cells
  • Interneurons
  • And many others known and yet to be characterised

  
• Age-related changes in cell morphology, molecular profile & function

  
• Spatial differences in cell expression profile

  
• Spatial variability in morphology depending on location e.g. microglia

  
• Dysfunctional neuronal & non-neuronal cells

  
• Neuronal cell specialisms

  
• Neuronal cells have large nuclei & local translation

  
• Three functions of neurons

  Sensory neurons

  • Conduct information from body to spinal cord (somatosensory) or brain
  • Relatively simple structure compared to other neurons – e.g. bipolar

  Interneurons

  • Connect sensory and motor activity of the CNS
  • Connect to sensory neurons, other interneurons and motor neurons
  • Variable shapes e.g. pyramidal, purkinje
  • Most common neuron

  Motor neurons

  • Information from brain and spinal cord to muscles
  • Located in lower brain stem & spinal cord

  Inhibitory

  Excitatory

  
• Neuronal subtypes can be further classified

  In the visual cortical GABAergic interneurons of mouse displayed ~30 distinctive subtypes using

  • Morphology
  • Whole genome gene expression
  • Electrical activity

  
• Neuronal networks – “Brainbow”

  Neurons in mouse hippocampus (dentate gyrus) - distinguished by ‘tagging’ them with different fluorescent colours

  
• Neuronal networks


  Pyramidal neurons Re-created from Cajal’s laws of neuronal branching

  
• Synapses – neural to neural contact

  
• Cells communicate to each other and their environment in the brain

  
• Non-neuronal cells carry out important functions in the brain

  Tissue Maintenance & Homeostasis

  • Clearing apoptotic cells
  • Neuron protection
  • Synaptic pruning
  • Tissue maintenance

  Protective

  • Trauma
  • Pathogens
• Protein aggregates signal as if pathogens - “Sterile Inflammation”

  Microglia respond to abnormal protein aggregates, dysfunctional & dying neurons, lipid damage