SHS 479 Neuroanatomy PDF

SHS 479 Neuroanatomy Neurons Nervous System Cells Basic function unit of the nervous system CNS PNS Cell types Neuron Glial cells (supporting cells) Estimated number of nerves and glial cells 10 glial cells : 1 neuron cell ratio Glial Cells Astrocytes Oligodendroglia...

SHS 479 Neuroanatomy Neurons Nervous System Cells Basic function unit of the nervous system CNS PNS Cell types Neuron Glial cells (supporting cells) Estimated number of nerves and glial cells 10 glial cells : 1 neuron cell ratio Glial Cells Astrocytes Oligodendroglia Schwann cells (highly common for brain tumors) Microglia Satellite cells Ependymal cells Astrocytes (Satellite Cells) Star shaped Found in CNS only Maintains environment for neural signaling Regulate blood flow Mitochondria transfer (powerhouse for the cell) Supply neurotransmitter precursors (building blocks) Stimulate synapse formation Responds to injury Satellite cells are the PNS equivalent Oligodendroglia (Schwann Cells) Oligodendrogila CNS Produces myelin and coats segments of axons Myelin (fatty covering the axons, speed up transmission of 150m/s) Covers short segments of axons May myelinate portions of multiple neurons Makes signal transmission more efficient Schwann cells are the PNS equivalent Insulates only a single axon in PNS  Multiple Sclerosis Autoimmune degeneration of myelin sheath in CNS Progressive- Unknown cause Relapsing MS 4 types to remember below (PRMS): Symptoms Common in females than males gradually get worse Severity varies in individuals with occasional relapses. Primary Progressive MS (PPMS): Symptoms gradually get worse over time. Secondary Progressive MS (SPMS): Starts with symptoms coming and going, then gradually gets worse. Guillain-Barré Syndrome Autoimmune degeneration of myelin sheath in PNS (Schwann Cells) Thought to be a reaction to a viral infection Paralysis (pain or numbness) beginning at extremities and progressing to the trunk Intact sensation Paralysis of respiratory muscles may require breathing support Tingling fingers and toes, sore back Maximum symptoms at 1 month Partial or full recovery over weeks to months Microglia Either CNS or PNS Considered part of the immune system Responds to pathogens and cell damage Phagocytosis Response to injury / infection Ependymal Cells Found only in CNS only Acts as filter Line the ventricular system Regulates production of cerebrospinal fluid (CSF) Circulation Basic Neuron Characteristics Soma (cell body) Neurites Axon (transmit info away) Dendrite (receive info) Myelin sheath More Detailed Schema Axon hillock – cell body connected to axon makes decision whether neuron will fire or not Nodes of Ranvier - small gaps in the myelin sheath that covers the axon of a neuron. These gaps are crucial for the rapid transmission of nerve impulses Neuron types Unipolar (single projection from one cell body, general sensations like touch or pain) Bipolar (one dendrite & one axon, special sensations vision/smell or hear) Multipolar (many projections = one axon & several dendrites, integrating and transmitting information) Anaxonic (no axon, many dendrites, do not directly transmit information but play a role in modulating the activity of surrounding neurons Alternative Classification Classification based on axonal length Golgi type I Long axon from inches to feet Sensory or motor tracts Responsible for transmitting info away over long distances Golgi type II Short axon Interneurons that connect with other adjacent cells Local info processing The Synapse Space between pre- and post-synaptic neurons Synaptic cleft 20 nm Site of signal transmission Synapse Components Pre-synaptic Terminal button (end of axon) Synaptic vesicles Neurotransmitter storage Exocytosis (cellular process used to transport molecules from inside the cell to the outside) Excitatory (more likely to fire) Post-synaptic Receptor sites Neurotransmitter binding Inhibitory (less likely to fire) Synapse Types Axodendritic (connect axons to dendrites) Excitatory Axosomatic (connect axons to cell bodies) Inhibitory Axoaxonic (connect axons to other axons) Modulatory = influencing the strength of other synapses Neuromuscular Junction Synapses also formed with glands and muscle fibers Overall mechanism is similar Pre-synaptic potential leads to post-synaptic potential Acetylcholine (Ach) dominates (excitatory neurotransmitter) Electrical synapses Allow direct electrical transmission between adjacent neurons Ion flow 3-4 nm synaptic cleft width Gap junctions (between pre – and post – synapses) Neural Function What is a neuron’s primary job? Signal transmission Electrochemical process Electrical Action potential Ionic energy, not electrical Chemical Neurotransmitter release The Action Potential Depolarization of a cell membrane with a resting negative charge -70 mV How would a neuron have a negative charge? Neurons maintains charge difference due to distribution of ions like sodium and potassium, and the activity of ion pumps. When a neuron sends an electrical signal (an action potential), these charges can change rapidly.  The Cell Membra Hydrophobic phospholipid bilayer Phospholipid Hydrophilic head – loves water Hydrophobic tail – hates water Lots of ion channels within membrane  Membrane Potential Generationpumps Sodium-potassium Active transport Membrane selectively permeable to 3 Na+ out and 2 K+ in More K+ inside than Na + outside (resting potential = -70mv) Slow, steady leak across concentration gradient Pulling The Trigger Combination of IPSPs and EPSPs from synaptic inputs Summed at the axon hillock Action potential generated if threshold is exceeded -55mV IPSPS (Inhibitory Postsynaptic Potential) EPSPS (Excitatory Postsynaptic Potential) Excitatory - raising voltage (positive) Inhibitory – lowering the voltage (negative) Initial Depolarization Voltage-gated ion channels open Na+ Repolarization Sodium-potassium pumps Voltage-gated ion channels At +30 mV Na+ closes K+ opens Hyperpolarization Membrane potential exceeds resting potential Ensures direction of action potential flow Refractory Period Absolute Neuron will not generate another action potential Deactivated Na+ channels Does not fire again Action potential flow in 1 direction Relative Stronger EPSP necessary/ to trigger another action potential (necessary to fire if there is a stronger stimuli) Hyperpolarization Simulation The Action Potential: Action potentials move at about 150 meters per second An action potential is all or nothing Functions like a digital converter converting analog signals into an “on” or “off” state. Depolarization to refractory period last a few milliseconds Channelopathies cystic fibrosis & fibromyalgia Saltatory Conduction Nodes of Ranvier Unmyelinated sections of the neuron Action potential “jumps” down the axon (makes conduction faster) Only occurs at nodes Clinical testing Speed transmission takes longer for MS because there is not much myelin.  Action Potential Review 1) At rest, -70mV Na + and k+ pumps are constantly ongoing. 2) When the stimulus is triggered, it reaches threshold at –55mv. Na + channel opens at depolarization. 3) Na+ channel closes (transition point) 4) Na+ channel closes while K+ channel opens. 5) At repolarization, 2K+ enters while 3Na+ leaves ongoing. At – 50mv, k+ channel closes. 6) At hyperpolarization, it takes a while for K+ channel to close and overshoot below resting point. 7) At –70mV, it returns back to the resting point. Neurotransmitters Definition / conditions Classes Synthesis / transport Storage / release Mechanism of effect Neurotransmitters Chemical messengers Must be present in pre-synaptic membrane Must be released in response to pre-synaptic depolarization Must be specific post-synaptic receptor to receive it Neurotransmitter Classes Small molecule (amines / amino acids) Acetylcholine+, dopamine(+/-), norepinephrine+, serotonin-, glutamate+, and GABA- Slow axonal transport (+) excitatory (-) Inhibitory Large Molecule peptides Fast axonal transport Synthesis Neurotransmitter Storage Small molecules (synthesized at the axon terminal, fires every single) Synaptic vesicles Neuropeptides (synthesized in the cell body , more energy to fire few times and lifespan) Secretory granules Exocytosis differences Small molecules leave faster than neuropeptides from the cell body Mechanism of Effect… Post-synaptic receptors Ligand-gated channels (ionotropic) Open to allow ions to flow across concentration gradient Excitatory post-synaptic potential (EPSP) Na+, K+, Ca++ Inhibitory post-synaptic potential (IPSP) Cl- Metabotropic receptors G-protein coupled receptor Secondary, longer-lasting effect Long-term potentiation Strengthening of synaptic connections Long- last effect (remember faster after a few practices) Neurotransmitters Over 100 known neurotransmitters Acetylcholine Dopamine Norepinephrine Serotonin Glutamate GABA Neuropeptides Acetylcholine (ACh) Primary PNS neurotransmitter Neuromuscular junction Cholinergic neurons (nerve cell use ACh to send messages) Myasthenia gravis (immune attack from the muscles, decreased ACh will cause more effort to take action = tired) Restricted CNS role Brainstem, base of forebrain, basal ganglia Critical for sleep/wake cycle Regulation of alertness, attention, memory, learning Alzheimer’s Regulated by acetylcholinesterase (AChE) Glutamate Main excitatory CNS neurotransmitter Most common neurotransmitter in CNS 40% produce glutamate 90% have glutamate receptors Heavily involved in learning/memory Synaptic plasticity (connections between neurons) Imbalance consequences (lack of attention, tired) GABA (Gamma-aminobutyric acid) Inhibitory CNS neurotransmitter Primary source of synaptic inhibition in CNS Blocks activity of other neurotransmitters Derivative of/related to glutamate Reduction associated with Huntington’s chorea (involuntary, inability to suppress movements, e.g. twitching) Sleep/wake cycle Dopamine Both excitatory and inhibitory CNS Inhibitory – indirect motor pathway Excitatory – direct motor pathway, pleasure, reward Produced in the brainstem (substantia nigra, tegmentum) and projects throughout brain Mesostriatal – Parkinson’s Mesolimbic – Addiction Mesocortical – Schizophrenia hearing/seeing things not there = positive symptoms emotional reduction = negative symptoms Epinephrine & Norepinephrine Excitatory CNS neurotransmitters Both hormones and neurotransmitters Synthesized in brainstem Epinephrine – projects to thalamus/hypothalamus Norepinephrine – projects to forebrain Both involved in fight-flight response (PNS in automatic system) Norepinephrine – more wide ranging effects on arousal/sleep  Serotonin CNS 95% of in blood platelets and gastrointestinal tract, involved with the regulation of: Sleep and wakefulness Overall level of arousal Low level of serotonin—depression, suicidal tendency, and mental illnesses Antidepressant drugs (e.g., Prozac, SSRIs) enhance synaptic serotonin levels Neuropeptides Separate class of neurotransmitters Large molecule Act primarily, but not exclusively as metabotropic agents Neuronal Responses to Injury Degenerative change types Axonal (retrograde) reaction Cell body changes induced by axonal injury Wallerian (anterograde) degeneration Changes to detached axonal segment Proximal Distal Axonal Reaction Chromatolysis Swelling of cell body Shifting of nucleus to periphery Dissolution of cellular organelles Synaptic terminals retract Possible cell death Phagocytosis Scar/cyst formation Possible recovery Increased protein synthesis to regenerate severed axon and prevent cell body from dying Wallerian Degeneration Degeneration of distal axonal segment and myelin sheath Cannot survive without supply materials from the cell body Axon disintegrates quickly (12-24 hours) Myelin sheath more slowly (3-7 days) Phagocytosis by microglia (3-6 months) CNS / PNS cytological differences Myelin producing cells PNS – Schwann cells CNS – Oligodendrocytes Connective fibrous tissue sheaths PNS – endo-, epi-, and perineurium covering axons (for recovery/protection) CNS – lack of additional covering layers (damaged due to lack of protective layers) Endoneurium: Innermost layer, supports and insulates individual axons. Perineurium: Middle layer, surrounds fascicles, acts as a protective barrier. Epineurium: Outermost layer, encases the entire nerve, provides overall protection and support. Axonal Regeration? CNS vs PNS Regeneration CNS Some growth/sprouting Cannot cross astrocytic scars Different protein expressions from PNS cells PNS Sprouting begins in 3-4 days Schwann cells and endoneurium guide sprouts Growth rate: 4 mm/day Functional restoration with reconnection Neuroglia Response Initial response Hyperplasia (Increase in cell number, leading to tissue or organ enlargement.) Hyptertrophy (Increase in cell size, resulting in tissue or organ enlargement.) Microglial response Phagocytosis Final outcome – Astrocytes (cluster & consume dead matter) Glial scar Cystic cavity Brain Tumors Primary (start within brain – such as astrocyte) vs metastatic (start somewhere else - common) Mechanism of damage Midline shift in skull, compressed tumor)