The Neuron PDF

The Neuron 23 September 2024 08:33 Aims: Describe the ultrastructure of the neuronal elements: soma, dendrites, and the axon Understand the function of the neuronal cytoskeleton and describe its components Describe the structure of the neuronal membrane and its role in maintaining r...

The Neuron 23 September 2024 08:33 Aims: Describe the ultrastructure of the neuronal elements: soma, dendrites, and the axon Understand the function of the neuronal cytoskeleton and describe its components Describe the structure of the neuronal membrane and its role in maintaining resting membrane potential and how it changes during an action potential Describe the types of axonal transport and outline the processes involved Things you should already know about neurons Neurons are the structural and functional units of the nervous system (central and peripheral) Neurons are highly specialised electrically excitable cells Neurons receive, process, and transmit info via electrochemical signalling They communicate via synapses Form neural circuits with other neurons Not the most vast in the nervous system (make up around 10% of the brain, glial cells take up a bigger percentage) The Neuron: a historical perspective Camillo Golgi (1843-1926) italian histologist - Golgi stained neurons, silver staining method made full neuron (soma, axon and dendrites) visible under microscope when, believed neurons were structural connected to each other all interconnected "The Neuron Doctrine" - neurons are discrete cells which are the basic structural and functional units of the nervous system Santiago Ramon y Cajal (1852 - 1934) Spanish neuroanatomist and histologist, used Golgi stain method to draw out brain circuitry and brain regions which highlighted the differences in structure, believed neurons are discrete cells that make up a circuit but are not physically connected Block 1 - The Neuron Page 1  connected Basic neuronal structure The Soma (Cell body) The soma contains the nucleus and surrounding cytoplasm ( known as perikaryon in neurons) Block 1 - The Neuron Page 2 Organelles of the soma The Nucleus - role in protein synthesis only (for enzymes etc used within the neuron), no replication in adult neurons Ribosomes - site of translation, free or associated with ER Endoplasmic reticulum (ER) - smooth or rough (Nissl bodies) - Nissl staining (neuronal stain) - More Nissl bodies in neurons than other cell types, highly metabolic, requires a lot of proteins Golgi apparatus - post-translational processing of proteins Mitochondria - site of ATP generation, highly numerous in neurons as highly metabolic cells, important for sodium potassium pump to maintain membrane potential Lysosomes - contain enzymes which break down organelles Lipofuscin bodies - contain lysosomal waste Block 1 - The Neuron Page 3  Myelin appears very dark as it contains a lot of protein (electron micrograph image may come up in exam, be able to tell where each part is) Lipofuscin Pigmented granules can be readily observed using light microscopy Appear yellow/brown, located very close to the nucleus "Wear and tear" pigment - higher levels of this pigment in aged cells; younger cells have a lower level of lipfuscin The cytoskeleton Neuronal cytoskeleton acts as a scaffold - shape and stability (but not static) Three structural components: microtubules (found throughout the neuron), microfilaments (found throughout the neuron) and neurofilaments (only found within axon and cell body) Block 1 - The Neuron Page 4 Microtubules Microtubules are composed of alternating strands of alpha and beta tubulin protein Approx 25nm Organised vertically? Microtubules are highly dynamic Have capping proteins at one end where no growing occurs Positive end able to have proteins added or removed allowing microtubule to shrink or grow Alpha and beta tubulin heterodimers form protofilaments - 13 surround a central pole Block 1 - The Neuron Page 5  Microtubules can have branches (found out recently) In example 6 branch to left and 5 branch to right where more protein is added to create another microtubule ? Microfilaments Block 1 - The Neuron Page 6  Thinnest fibres of the cytoskeleton (approx 5nm diameter) Each microfilament formed by two actin polymers (colour coded so you can see its two different strands but both made of actin) G-actin monomers combine to form actin polymers (F-actin) Found throughout the neuron (especially in neurites) Form a dense network underneath neuronal membrane (essentially tethered) Role in changing neuronal shape and motility, important in dendrites as they can increase in number and change shape/size and microfilaments permit this - known as synaptic plasticity Actin-binding proteins (spectrin-fodrin, ankyrin) Neurofilaments Intermediate filaments (approx 10nm diameter) 'Bones' of the cytoskeleton Strong and stable - not dynamic like microtubules and microfilaments Not polarised at all? Often called the bones of the cytoskeleton 2 monomers twist together to form a dimer, the dimer coils with a dimer to make a protofilament which then combines within another to make a protofibril and 3 photofibrils make a neurofilametn, nicely organised Each neurofilament is composed of 3 photofibrils Biomarker of neurodegenerative disease if neurofilament is detected in CSF: ALS, MS, & Huntington's Neurofibrillary tangles - Alzheimer's disease Block 1 - The Neuron Page 7 Pathology of the cytoskeleton Neurofibrillary tangles - Alzheimer's disease Neurofilaments become tangled in Alzheimer's disease The Neuronal Membrane Phospholipid bilayer - barrier to isolate the cytosol from the extracellular fluid Transmembrane proteins control passage of ions in/out of the neuron - Receptor protein - Channel protein - NA-K pump (important in maintance of neuronal membrane potential, uses ATP to actively move 3 sodium out of the cell and bring 2 potassium in) - Voltage gated channel The neuronal membrane is therefore semi-permeable Diameter approx 5nm Block 1 - The Neuron Page 8 Resting membrane potential Membrane potential at rest: -70mV Voltage gated channels closed High K+ inside, high Na+ outside (low K+ outside, low na+ inside) Depolarised membrane : Membrane potential becomes less negative due to a stimulus Voltage gated Na+ channels open Na+ moves into cell down its concentration gradient making the cell more positive Repolarisation/hyperpolarisation: Voltage gated Na+ channels close Delayed opening of voltage gated K+ channels (same stimulus but takes longer for them to open) Block 1 - The Neuron Page 9  open) K+ moves out of cell Hyperpolarisation - the neuronal membrane potential comes down as it becomes more negative than it was before The Action Potential Block 1 - The Neuron Page 10  Sodium influx at -55mV which then makes cell more positive causing action potential Potassium channels open and causes cell to become more negative Both channels close and membrane potential becomes restored? Dendrites "dendrite" derived from Greek for "tree" - dendritic branches Component of synapses - postsynaptic membrane - receptors Dendritic spines (can be 100s and 1000s of them?)- each spine typically forms a single synapse High number of spines - high neuronal connectivity; greater opportunity to form circuits with other neurons Synapses are formed at dendritic spines ? Protein dense Spines are dynamic and can change shape due to microfilaments (synaptic plasticity) Block 1 - The Neuron Page 11 Dendrite shapes Thin dendrites - think neck and small head Mushroom - thick neck, flat head Stubby - no neck and very flat The Axon Specialised for the transmission of electrical impulses - AP propagation Axons can be myelinated (Group A&B fibres; b is not as fast as a ) or unmyelinated (Group C fibres; slow conducting e.g. pain) Axon hillock - site of summation of EPSPs and IPSPs from synapses (combination of excitatory and inhibitory stimuli and is where it is decide if an action potential will occur) Initial segment - action potential generation Action potential conduction velocity - determined by axon diameter and myelin Axons may branch to form axon collaterals Summation of EPSPs and IPSPs Block 1 - The Neuron Page 12  A and b excitatory (e.g. glutamate), make it closer to threshold potential as more positive (depolarisation) C inhibitory (e.g. GABA), make it more negative If each fires on their own it is not enough to cause an action potential If a and b fire together spatial summation occurs and threshold is reached to trigger an action potential If a and c fire at the same time there would be no change as they cancel each other out Axonal (axoplasmic) transport Axons lack ribosomes and cannot synthesise protein Secretory proteins and organelles must be transported from the soma to the axon Proteins are also transported back to soma from the axon terminal e.g. vesicles, growth factors Microtubules act as the "tracks" for transportation as they are highly organised in a longitudinal manner Axoplasmic transport can classified as fast (50-400mm/day) or slow (