Neurons and Glia: A Study Guide PDF

Neurons and Glia TOPICS: 1.1 Features of Neurons 1.2 Genes and the nervous system 1.3 Glia TEXTBOOK: Ch. 1 pg. 1-8, 20-21, Box 1A Levels of Analysis In Neuroscience Atoms Molecules (protein, DNA, etc.) Individual Cells Pairs of c...

Neurons and Glia TOPICS: 1.1 Features of Neurons 1.2 Genes and the nervous system 1.3 Glia TEXTBOOK: Ch. 1 pg. 1-8, 20-21, Box 1A Levels of Analysis In Neuroscience Atoms Molecules (protein, DNA, etc.) Individual Cells Pairs of cells connected by synapses Networks of interacting cells Systems in the brain that regulate behavior Behaving Animal Groups of animals  Alzheimer’s Disease Neurodegenerative – Loss of short term memory, decline in cognitive functions >15,000 Nova Scotians now living with Alzheimer’s 50% of people over 85 develop Alzheimer’s Cost is set to increase 10 fold due to aging population Questions at cellular level Why + where do cells die? Why are some cells not affected? Prevention / Cure? Biomarkers for early detection Pharmaceutical targets 1.1 Features of Neurons Neurons are the most anatomically diverse cell in the body Yet most neurons have a number of common features… Dendrites Cell body Axons Neuronal Diversity Good understanding of neuronal diversity established by the early 20th century Pioneering cell-staining method by introduced by Camillo Golgi Gogi Stain: tissue washed with silver salts, a few neurons take up the silver and are stained black (A & B) Golgi championed the reticular theory: all neural tissue is connected in a continuous net Santiago Ramon Y Cajal used Golgi’s stain and meticulous microscopy to argue for the neuron doctrine: each cell (neuron) was a discrete entity * Golgi and Cajal shared a Nobel Prize in 1906 Neuronal Diversity More recently, neural structure and organization has been visualized with: fluorescent dyes injected into individual neurons using specialized equipment Nissl or cresyl violet stains that colour parts of the cell body to visualize cellular organization Genetically encoded fluorescent proteins Dendrites, axons, and synapses allow neurons to perform their principle function - signaling AKA information transmission intracellular signaling - from one part of the cell to another intercellular signaling – communication between cells The Axon Tube-like process exiting from the axon hillock on the soma Interneurons have relatively short axons Projection neurons have longer axons Transmits electrical signals rapidly along its length Ch. 2-4 explore the membrane properties and ion channels that allow electrical signaling in neurons The synapse Where pre-synaptic axon terminals (synaptic boutons) meet post-synaptic dendrites The site of intercellular information transfer Term ‘synapse’ comes from the Greek word “connect” Coined by Sir Charles Sherrington ~100 years ago Hypothesized its existence from spinal cord reflexes years before any anatomical correlate Ch 5-7 will talk about synaptic transmission, receptors, and intracellular signaling The Dendrites Usually acts as synaptic input site Integrates information from other cells Some dendritic trees can be highly branched Some dendrites have numerous finger-like projections called dendritic spines Highly plastic structures Ch. 8 will talk about receptors and plasticity  1.2 Genes and the Brain The source of neuronal diversity is not well understood thought to be at least partially under genetic control Sequencing the genome has not produced as many insights into brain function as with other organs/systems Why not? Genes, the nervous system, and behavior Genes ? Environment ? ? ? Neuronal Behavior ? Structure/Function Genes influence behavior but… Large gaps in our understanding of: How genes influence neural structure/function How neurons produce behavior How environment influences gene expression and neural development to ultimately affect behavior Brain-gene interactions are difficult to understand because of the complexity of the brain Human brain: ~100 billion neurons 1015 synapses in the neocortex A typical neuron has ~ 5,000 – 30,000 synapses (just a few up to 200k depending on cell type) May different neuronal subtypes ~20,000 protein- coding genes in human genome Not all involved in brain function e.g. 1) Why brain / gene interactions are not straight-forward Complexity of the human brain probably results from extra genes unique to humans, right? Mice actually have a larger number of genes than humans But… only ~75 million neurons fewer synapses than in humans as well e.g. 2) Why brain / gene interactions are not straight-forward Drosophila axon guidance receptor (DSCAM) undergoes alternate spicing when the gene’s DNA is being transcribed to mRNA Exons (expressed nucleotide sequences) can be retained, or spiced out with introns (intervening nucleotide sequences) Creates a receptor with 38,016 possible variants (more that double the number of predicted genes in the entire genome) 1.3 Glia As The stereotypical neuron: s on een TV  Glia outnumber neurons ~3:1 3 broad categories: i) Astroglia ii) Oligodendroglia iii) Microglia Glial cells retain their ability to divide throughout life Astrocytes Star-like structure Maintain chemical homeostasis Provide structure / scaffolding for other CNS components Isolates and insulates neurons from each other Astrocytes – other functions 1. component of blood brain barrier - surround vascular endothelial cells Prevent immune cells, molecules, or pathogens from entering brain Astrocytes also shuttle nutrients (lactate) from blood vessels to neurons ~20% of body’s energy required to fuel the brain 2. involved in glutamate uptake Astrocytes – wide reaching synaptic influence 1 astrocyte can interact with 2 million synapses and influence their function. Astrocyte stem cells A subpopulation of astrocytes are glial stem cells Located near the ventricles In the subventricular zone (SVZ) Adjacent to ventricular zone blood vessels Give rise to: more stem cells, neurons, mature astrocytes, and oligodendrocytes Oligodendrocytes Myelin producing cell in the CNS A single oligodendrocyte can provide 30-50 myelin internodes Fewer cell processes than astrocytes Functionally (but not structurally) similar to Schwann cells in the Peripheral Nervous System (PNS) Oligodendrocytes Also supplies axons with fuel to support high metabolic activity Oligodendrocytes release lactate too (astrocytes described 1st) after myelin formation especially important for survival of motor neurons Oligodendrocytes and ALS(?) Amyotrophic lateral sclerosis (ALS) degeneration of large motor neurons other brain neurons spared Voluntary movement lost over 1 – 5 years Walking, talking, swallowing, breathing Death usually due to respiratory failure No effect on sensation or cognition Stephen Hawking Oligodendrocytes and ALS(?) Exact cause of ALS unknown Recent theory Motor neurons cannot absorb lactate supplied by oligodendrocytes. Die from lack of energy compounds Motor neurons may be especially sensitive because of long axons. Energy supply from cell body may be less efficient Lee et al., (2012) Nature, 487:443-448. Oligodendrocyte stem cells Oligodendrocyte precursors (polydendrocytes) are scattered throughout the white matter Give rise to mature Oligodendrocytes, and some Astrocytes Microglia The CNS is an ‘immunologically privileged’ organ due to Blood Brain Barrier Fewer immunological defenses than other body areas Microglia share properties with macrophage (immune) cells found in other tissues Scavenge cellular debris Microglia secrete signaling molecules such as cytokines Modulate local inflammation Can affect cell survival after damage  Microglia Aberrant inflammation may contribute to neuronal damage in some neurodegenerative diseases (e.g. Alzheimer’s Disease).