Neurons And Glia

Question 1

Levels of analysis in neuroscience

Answer 1

• atoms
• molecules
• individual cells
• pairs of cells connected by synapses
• networks of interacting cells
• systems in the brain that regulate behaviour
• behaving animal
• groups of animals

Question 2

Alzheimer’s disease

Answer 2

• neurodetengerative
  
  • loss of short term memory, decline in cognitive functions
• 50% of people over 85 develop Alzheimer’s
• cost of treatment will increase 10fold due to aging population

Question 3

Neurons

Answer 3

• functional unit of NS
• most anatomically diverse cell in the body
• all contain dendrites, cell body, and axon

Question 4

Neuronal diversity

Answer 4

• pioneering cell-staining method introduced by Camille Golgi and utilized by S. Ramon Y Cajal
• Golgi stain: tissue a shin with silver salts, a few neurons take up the silver and are stained black

-more recently developed fluorescent dyes can be injected into individual neurons using specialized equipment

Question 5

Signalling

Answer 5

• principle function
• facilitated by dendrites, axons, and synapses
• intracellular: from one part of cell to another
• intercellular: communication between cells

Question 6

Axon

Answer 6

• tube-like process exiting from axon hillock on the soma
• interneurons have relatively short axons
• projection neurons have longer axons
• the axon transmits electrical signals rapidly along its length

Question 7

The synapse

Answer 7

• where pre-synaptic axon terminals (synaptic boutons) meet post-synaptic dendrites
• site of intercellular information transfer
• ‘synapse’ comes from Greek work ‘connect’
  
  • coined by sir Charles Sherrington
  • hypothesized it’s existence from spinal cord reflexes years before anatomical correlate

Question 8

Dendrites

Answer 8

• some dendritic trees can be highly branched
• usually acts as synaptic input site
  
  • integrates information from other cells
• some dendrites have numerous finger-like projections called dendritic spines
  
  • highly plastic structures

Question 9

Neuronal structure

Answer 9

• maintained or changed by the cytoskeleton
• cytoskeleton is highly plastic during developmental (atonal path finding/ growth cone), and acts as a highway for molecular motors
• dendrites composed of microtubules (tubulin) and actin
• axon composed up intermediate filaments (neurofilament) and microtubules
• synaptic boulb composed of actin mainly and microtubules

Question 10

Genes and the brain

Answer 10

-source of neuronal diversity not well understood
-partially under genetic control
-genes influence neuronal structure/function which influences behaviour
-unsure how genes influence neuronal structure, how neurons produce behaviour, and how environment and genes interact to alter neuronal function
-

Question 11

Complexity of brain

Answer 11

• makes brain-gene interactions hard to understand
• human brain: ~100billion neurons
• 10^15 synapses in the neocortex
• a typical neuron has ~5,000-100,000 synapses
• thousands of different neuronal types
• 20,000 protein-coding genes in human genome
• not all involved in brain function (about 14,000 are)

Question 12

Genes, nervous system and behaviour

Answer 12

• genetic control of neuronal structure/function not straight forward
• seems that complexity of human brain results from extra genes unique to humans?
  
  • NO
  • mice have more genes than humans but less neurons and fewer synapses
• eg. Drosophila axon guidance receptor (DSCAM) undergoes alternate splicing when being transcribed which creates a receptor with 38,016 possibilities… double the number of predicted genes in entire genome

Question 13

Neuronal system and diversity

Answer 13

• originally begin as progenitor cells
• generation of neuronal diversity causes 20^9 neuronal types and subtypes
• cell death and selective pressure based on experience causes more variation
• cell maturation and signal amplification by changes in synaptic activity created dynamic diversity mediated by activity

Question 14

Example where genes can be tied to NS

Answer 14

• autosomal recessive primary microcephaly (MCPH)
• results in a small both otherwise normal cerebral cortex associated with mild to moderate mental retardation
• most common cause is a homozygous mutation of a gene called ASPM
• ASPM (abnormal spindle like microcephaly associated) gene is essential for normal mitotic spindle function in embryonic neuro lasts
• mouse version (ASPM) expressed specifically in primary sites of prenatal cerebral cortical neurogenesis
• across species, ASPM homologs differ in number of IQ domains
  
  • c. Elegans: 2 repeats
  • drosophila (asp): 24 repeats
  • mice (Aspm): 61 repeats
  • humans (ASPM): 74 repeats
• seems like more IQ domains in this gene leads to bigger brains

Question 15

Glia

Answer 15

• Glia outnumber neurons 3:1
• 3 broad categories
  
  • atroglia
  • Oligodenroglia
  • microglia

-glial cells retain their ability to divide throughout life

Question 16

Astrocytes

Answer 16

• star like structures
• maintain chemical homeostasis
• provide structure/scaffolding for other CNS components
• isolates and insulates neurons from eachother
• component of blood brain barrier
  
  • surround vascular endothelial cells
  • astrocytes shuttle nutrients (lactate) from blood vessels to neurons
  • 20% of body’s energy required to fuel the brain
• involved in glutamate uptake
• 1 astrocyte can interact with 2 million synapses and influence their function

Question 17

“Neuronal threesome”

Answer 17

• astrocytes have extensions that wrap around the gaps or synapses between neurons
• one neuron signals to another by releasing neurotransmitters into the synapse
• the neurotransmitters are also taken up by astrocytes
• once activated the astrocytes experience an increase in intracellular calcium and release NT of their own which can inhibit or enhance synaptic activity

Question 18

Astrocyte stem cells

Answer 18

• a sub population of astrocyte are glial stem cells
• located near ventricles (in the subventricular zone (SVZ) and adjacent to ventricular zone blood vessels)
• give rise to more stem cells, neurons, mature astrocytes, and oligodendrocytes

Question 19

Oligodendrocytes

Answer 19

• myelin producing cell in CNS
  
  • a single one can provide 30-50 myelin internodes
• few cell processes that astrocytes
• functionally similar to Schwann chills in PNS
• supplies axons with fuel to support high metabolic activity
  
  • oligodendrocytes release lactate after myelin formation
  • especially important for survival of motor neurons

Question 20

Oligodendrocytes and ALS

Answer 20

• ALS (amyotrophic lateral sclerosis
• degeneration of large motor neurons
• voluntary movement lost over 1-5 years
• death usually due to respiratory failure
• no effect on sensation or cognition
• exact cause unknown
• possibly that motor neurons cannot absorb lactate supplied by oligodendrocytes
  
  • die from lack of energy compounds
  • motor neurons especially sensitive because of long axons
  • energy supply from cell body may be less efficient

Question 21

Oligodendrocyte stem cells

Answer 21

• oligodendrocyte precursors (polydendrocytes) are scattered throughout white matter
  
  • give rise to mature oligodendrocytes and some astrocytes

Question 22

Microglia

Answer 22

• the CNS is an immunologically privileged organ due to BBB
  
  • fewer immunological defences than other body areas
• microglia share properties with macrophage immune cells
  
  • scavenge cellular debris
• microglia secrete signalling molecules such as cytokines
  
  • modulate local inflammation
  • can affect cell survival after damage
• inflammatory state may contribute to neuronal damage in many neurodegenerative diseases (eg. Alzheimer’s)