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Flashcards in Neurons And Glia Deck (22)
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Levels of analysis in neuroscience

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


Alzheimer’s disease

-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



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


Neuronal diversity

-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



-principle function
-facilitated by dendrites, axons, and synapses

-intracellular: from one part of cell to another

-intercellular: communication between cells



-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


The synapse

-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



-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


Neuronal structure

-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


Genes and the brain

-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


Complexity of brain

-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)


Genes, nervous system and behaviour

-genetic control of neuronal structure/function not straight forward
-seems that complexity of human brain results from extra genes unique to humans?
-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


Neuronal system and diversity

-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


Example where genes can be tied to NS

-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



-Glia outnumber neurons 3:1
-3 broad categories

-glial cells retain their ability to divide throughout life



-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


“Neuronal threesome”

-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


Astrocyte stem cells

-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



-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


Oligodendrocytes and ALS

-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


Oligodendrocyte stem cells

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



-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)