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Chapter 3

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University of Toronto Scarborough
Janelle Leboutillier

CHAPTER 3 100s of 1000s pounds of puffer fish (fugu) are consumed in Japan (Oct-March). 100-200 people die from the effects of tetrodotoxin (TTX). TTX blocks the formation and transmission of electrical signals (action potentials) within nerve cells. - It blocks the movement of Na across the cell membrane that makes signaling possible. - Puffer fish are not poisoned by TTX (by its own TTX or by consumption of other TTX species) since its sodium channel has specific adaptations. Neurons and Glia - 2 cell types: neurons and glia - Neuron: information processing and communication - Glia (glue): support activities of neurons; 10-50 glia per neuron Organelles are found in the cell body/soma. Branches of cell- axons/dendrites Neuron Membranes - Separates intracellular fluid from extracellular fluid - 2 phospholipid molecules wide -9 - 5 nanometers thick (1 nm= 1 billionth of a meter or 10 m) - Permeability is controlled by suspended protein structures. o Ion channels- ions move passively, selective  E.g. voltage-dependent channels- open/close in response to the electrical status of adjacent areas of the membrane.  Ligand gated channels- open when in contact with specific chemicals. o Ion pumps- requires energy, selective  Sodium-potassium pumps  Maintain differences in chemical composition between intra-and-extra-cellular fluids.  3 Na out and 2 K in  Use 20-40% of brain energy 2+  Calcium pumps- similar function, pump Ca out  Important to maintain low levels of Ca in cells. o Amino acid composition of pump/channel determines ion selectivity. Neural Cytoskeleton Maintains shape of neuron. 3 filament types, which also move elements within the cell and anchor channel and receptor proteins in membrane: 1. Microtubules - Largest fiber - Hollow tubes with diameter of 25nm. - Responsible for movement of materials within the cell - Movement along microtubules: o From cell body to axon terminal: anterograde transport o Back to cell body from periphery: retrograde transport - Alzheimer’s disease: initial memory loss, followed with progressive decline in cognitive and physical functions leading to death. o Symptom: presence of neurofibrillary tangles consisting of protein called tau. o In healthy brain, tau connects adjacent microtubules and holds them in place. o In Alzheimer’s, tau levels elevate. In response, neuron adds more P to tau protein causing it to disconnect from microtubules and tangle- hindering the cell’s ability to signal and maintain structure. o Neuron folds in on itself and collapses. 2. Neurofilaments - Middle sized, most common fiber in neuron - Diameter: 10 nm - Similar structure to hair and strong for their size. - Run parallel to length of axon and provide structural support 3. Microfilaments - Diameter: 3-5nm - Mostly located in branches of neuron- thus may participate in changing the shape and length of these structures during development and in response to learning. Neural Cell Body/Soma - Contains nucleus o Which contains nucleolus- builds organelles like ribosomes (produce proteins alone or with endoplasmic reticulum). o Proteins constructed by ribosomes on RER, then moved by the SER to the Golgi apparatus, which inserts completed proteins into vesicles. - Mitochondria o Extracts oxygen and pyruvic acid from sugar in intracellular fluid and makes ATP. Dendrites - Greek word- tree - Info is received - Greater area of dendritic membrane a neuron has, the larger the number of synapses it can form with other neurons. - Some form knobs called dendritic spines. o Can change shape based on amount of activity occurring at the synapse- contribute to processes of learning and memory o Abnormal spines - underling cause of some types of human mental retardation.  Spines of people with mental retardation are unusually long and thin.  Pupurta observed that the spines of mentally retarded children were similar to the undeveloped ones of fetuses. I.e. their spines failed to mature normally in response to learning.  Protein called fragile X mental retardation protein (FMRP) is essential to normal maturation of dendritic spines.  Mice lacking the gene encoding FMRP show spine immaturity similar to Purpura’s samp Axon - Each neuron has 1 axon. - Responsible to carry neural messages to other neurons. - Axon hillock: between cell body and axon; cone shaped - Action potentials arise in the axon hillock and travel down the axon. -6 - Diameter varies- range from 1 um (10 m) to 25 um o Invertebrates, e.g. squid- 1mm o Diameter crucial to signaling speed- the larger, the faster - Vertebrate axons are covered with myelin, which allows for faster signaling in spite of smaller diameters. - Axon length varies. o Ones that barely extend from cell body and communicate with adjacent cells- local circuit neurons o Others with long axons- projection neurons - Ends of axons are divided into branches called collaterals. - At the end of each collateral is a swelling called the axon terminal. o Terminal contains large numbers of mitochondria and synaptic vesicles containing chemical messengers.  Vesicles- 50 nm in diameter - Most of the CNS and PNS are myelinated. o PNS can be unmyelinated- smallest diameter axons usually unmyelinated. - Myelin formed by certain types of glia that wrap themselves or their branches around segments of the axon. o Axon hillock is never myelinated. o Between myelin segments are the nodes of Ranvier (every 0.2 mm to 2.0 mm apart). o Large diameter axons have thicker myelin and greater distances between the nodes of Ranvier. - Advantages of myelin: o Increase of signaling speed in spite of small diameter o Space is important in nervous systems. o Reduces energy requirements of neurons by decreasing amount of work done by Na-K pumps. Structural variations in neurons Another way to classify neurons is according to number of branches extending from the cell body. Unipolar neurons: - Single branch extending from cell body - Typical of invertebrates - Found in sensory systems and ANS - E.g. some involved with somatosenses (touch, pain, temperature). - Just beyond the cell body, the branch divides in 2. o One part extends back to CNS o Other part extends to skin and muscle Bipolar neuron - 2 branches: 1 axon, 1 dendrite - Important in sensory systems, including the retina of the eye. Von Economo neuron - Bipolar neuron - Developed in primate evolution - Found in humans and great apes, but not in lesser apes or monkeys. - Their numbers and cell body size are larger in humans than in great apes. - Occur in anterior cingulate cortex (ACC), and in junction of the frontal lobe and insula area of the temporal lobe. - Designed to provide fast, intuitive assessments of complex situations. Multipolar neuron - Most common type of neuron n vertebrate nervous system - Many branches extending from cell body: 1 axon and many dendrites - Can be further classified according to shape. o Pyramidal cells in the cerebral cortex and the hippocampus have cell bodies shaped like pyramids. o Purkinje cells of the cerebellum have dramatic dendritic trees that allow a cell to form 150,000 synapses. Functional Variations in Neurons Sensory neurons, motor neurons (transmit commands of CNS to muscles/glands), interneurons (most common type; bridge between sensory and motor neurons) Glia Support activities of neurons. Categorized by size: macroglia or microglia Macroglia types: 1. Astrocytes - Support functions of neurons - Star-like shape - Most common glia - Provide structural matrix for neurons (otherwise they would float around in ECF) - Form connections with blood supply of brain o Allows them to transfer glucose and other nutrients to neurons. o Along with brain capillaries, they contribute to blood-brain barrier that prevents blood toxins from entering the brain. - Surround and isolate area of synapses so neurotransmitters are contained. - Can gather molecules from the synaptic gap (e.g. excess K) - Occasionally can be harmful: o When CNS neurons are damaged, a mobile astrocyte moves to the area and digests the dead neurons. This causes the formation of scar tissue that prevents axons/dendrites from rebuilding their connections.  Good to contain damage, but prevents neural regrowth. - It was noticed that neurons grown in Petri dishes along with astrocytes were 10 times more responsive than neurons grown alone. o Barres et al found evidence that astrocytes were signaling the neurons to build synapses. I.e. they are important in learning and memory, which involve the reorganization of synaptic connections between neurons. - Play important role in chemical signaling in the brain by influencing adjacent neurons and other astrocytes by releasing glutamate and ATP. o Glutamate is am excitatory chemical messenger in the brain. o Adenosine (byproduct of ATP) is inhibitory. o Thus, astrocytes both excite/suppress activity of neighboring neurons & astrocytes. - Improved understanding of astrocytes’ role in signaling is helping in managing many brain diseases. o Too much glutamate kills neurons. E.g. if glial cells release too much glutamate in response to damage (e.g. a stroke), nearby neurons die. o Limiting glutamate release by astrocytes may reduce loss of neurons associated with common brain disorders. 2. Ogliodendrocytes - Myelinate axon fibers in CNS - Each one puts out a number of branches that wrap around nearby axons- each myelinates about 15 neurons. o Thus contribute to structural stability of the brain and spinal cord. 3. Schwann cells - Myelinate axon fibers in peripheral nerves exiting CNS. - Each myelinates 1 neuron. - It takes many Schwann cells to myelinate a single peripheral nerve. - Can guild regrowth of damaged axons (unlike ogliodendrocytes)- allowing us to reattach severed limbs/fingers. o Surgeons can transplant heads/faces from cadavers to living people- nerve regrowth provided sensation and motor control. MS: progressive demyelination of the nervous system; neural signaling doesn’t work leading to symptoms ranging from mild (e.g. increased fatigue) to severe (e.g. vision and mobility problems) to death. Microglia - Clean up dead cells, neurons and glia. - At rest, branches of microglia reach out and sample their immediate environment. - If they find molecules that relate to cell damage (head injury, stroke, etc.), they travel to the location of injury and digest the debris. - Uncontrolled activation can damage brain due to their release of inflammation causing substances. - Observed to digest healthy cells near damaged cells. - Inflammation caused by microglia activation contributes to neurodegenerative diseases (e.g. Alzheimer’s, Parkinson’s, MS). The Generation of the Action Potential - Generated in the axon hillock of the presynaptic neuron - At axon terminal, electric signal becomes chemical signal by release of neurotransmitters. - Energy to generate an AP is provided by the characteristics of the intra-and- extra-cellular fluids. Ionic Composition of Intra-and-Extra-Cellular Fluids ECF- large concentrations of Na & Cl and few K (like seawater) ICF- high [k] & [negatively charged proteins] and low [Na] & [Cl] Neuron is more – inside than outside. - Can record difference by inserting a tiny glass microelectrode though the membrane of the neuron itself. - Use a voltmeter to measure difference between microelectrode and wire placed in ECF near cell. - Difference between + and – terminals in a car battery is 12 volts. - In a neuron, its 70 mV. - Outside environment is assigned 0, thus difference across membrane is - 70mV (resting potential). Movement of Ions Diffusion: tendency of molecules to distribute themselves equally within a medium (e.g. air/water). - Moves molecules along a [] gradient from high [] to low []. Another cause for movement is electrica
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