Topic 3 - Neurophysiology Basics.pdf

Topic 3 Neurophysiology Basics • Membrane Potentials • The Action Potential • Action Potential Properties • Propagation • Conduction Velocity and Myelination • Neurotransmission • Signal Integration Mikasen, Action Potential – 2005 Goals • Give a general overview of action potentials and neurotra...

Topic 3 Neurophysiology Basics • Membrane Potentials • The Action Potential • Action Potential Properties • Propagation • Conduction Velocity and Myelination • Neurotransmission • Signal Integration Mikasen, Action Potential – 2005 Goals • Give a general overview of action potentials and neurotransmission • Understand influence of particular ions on electrical properties of and processes within the neuron. • Provide baseline knowledge of neurotransmission process • Explain how incoming signals from many neurons integrate to influence firing rate of a neuron Neurophysiology Study of chemical and electrical signals within neuronal cells to process and transmit information Setting the Stage Plasma or cell membrane separates intracellular environment from extracellular environment Establishing electrical potentials The neuron’s interior is usually more negatively charged than the exterior space: a membrane potential (Vm) exists! Resting potential When no inputs are acting upon a neuron, it will settle at its resting membrane potential (Vrest) • Vrest ≈ –70 millivolts (mV). Core ions are found in different concentrations • Na+ and Cl- highly concentrated outside of the cell • K+ is highly concentrated inside of the cell. Presence of different ion concentrations across the cell membrane creates Vm Concentration gradients Diffusive force pushes ions down their concentration gradient Crossing the membrane Leak channels Ion channels allow ions to cross the membrane • Leak channels always open • Gated channels open or close in response to environmental signals Effects of ionic movement Ions crossing the membrane can change Vm • Cations (Na+, K+) leaving or anions (Cl-) entering cell = more negative interior • Cations entering or anions leaving cell = more positive interior Terminology for changes in Vm Depolarization  interior less negative than Vrest • Na+ currents Hyperpolarization  interior more negative than Vrest • K+ and Cl- currents Keeping ionic concentrations consistent Na+/K+ pump - moves 2 K+ in, 3 Na+ out of the neuron using 1 molecule of ATP • Keeps ion concentrations constant  diffusive force unchanged over time! Stimuli that change Vm Stimuli given to a neuron produce changes in Vm that are local and graded • Local — as potential travels away from its source and across the membrane, it decays • Graded – larger stimuli  larger responses (and visa versa) The threshold Graded potentials from hyperpolarizing stimuli always decay back to Vrest over time. Depolarizing stimuli also decay back to Vrest, but only if they fail to reach the threshold. If threshold is reached, the cell will fire an action potential Phases of an action potential Three key phases of the action potential: • Depolarization • Repolarization • Hyperpolarization The action potential progresses through five distinct stages 1. Initiation – neuron depolarized to threshold 2. Depolarization/Rising Phase – interior of neuron rapidly becomes more positively charged 3. Repolarization/Falling phase – interior of neuron rapidly returns to negatively charged status 4. After-hyperpolarization/Undershoot – neuron bypasses Vrest and is briefly hyperpolarized 5. Return to rest – the neuron returns to Vrest Triggering the opening of gates Activation gates open in response to a condition being met. • Voltage gates open when Vm reaches a certain threshold voltage • Ligand gates open when a chemical (ligand) binds to the channel Neurotransmitter receptor! Voltage-gated Na+ channels trigger the rising phase Voltage-gated Na channel (VGNC) • Na+ channel that opens extremely quickly at threshold (-50 mV) • Massive Na+ current = strong depolarization • Snaps shut within a 1-2 milliseconds Voltage-gated K+ channels trigger repolarization and hyperpolarization Voltage-gated potassium channels (VGKCs) • K+ channel that is sluggish/slow • Opens at threshold, does not fully open until VGNCs snap shut. • Massive K+ current = strong hyperpolarion Undershoot/AHP VGKCs are slow to open and close! • When Vm returns to Vrest not all the VGKCs have closed yet. Undershoot or afterhyperpolarization (AHP): brief period of hyperpolarization after AP Returning to Vrest As VGKCs close, the membrane returns to Vrest Properties of the AP All-or-none principle: 1. Neuron either fires or does not. • No such thing as a partial AP 2. AP amplitude always the same. • Larger stimuli ≠ larger AP Properties of the AP Frequency-coding • Increased stimulus intensity = more APs produced Limits to AP frequency Refractory period – period after an AP where the membrane is unresponsive to firing additional APs APs travel down the axon as they occur APs are not static, unmoving events! Na+ spreads out as it enters neuron, triggers APs in neighboring sections of the axon This is known as propagation APs always initiate at the connection between soma and axon APs originate at the axon initial segment (AIS) • next to the axon hillock Incredibly high concentration of VGNCs AP travel in only one direction due to the refractory period APs travel from AIS  axon terminals Behind the AP the membrane is refractory  unidirectional travel How Is an Axon Like a Toilet? AP velocity Conduction velocity - speed of AP propagation • Determined by axon diameter and myelination. • Larger diameter axons = faster conduction • Myelination = faster conduction Myelination Myelin is created by: • Oligodendrocytes in the (CNS) • Schwann cells in the (PNS) Nodes of Ranvier — gaps between sections of myelin where the axon is exposed Internodes – sections of axon covered by myelin The AP only occurs at nodes of Ranvier in a myelinated axon Na+ ions flow at high speed along internodes • Current decays, but still strong enough to depolarize VGNCs to threshold at next node AP is refreshed at nodes of Ranvier, refreshing the Na+ current to be sent down the next internode. The leaping AP Saltatory conduction (from the Latin saltare – “to hop” or “to jump”) • AP appears to “jump” from node of Ranvier to node of Ranvier Transition from electrical to chemical signal Synaptic vesicles –small, spherical organelles located in the presynaptic terminal • filled with neurotransmitter (NT) molecules. Transition from electrical to chemical signal Voltage-gated calcium channels (VGCCs) – expressed densely on presynaptic terminal (esp in active zone!) Calcium ions (Ca2+) highly concentrated outside the neuron Transition from electrical to chemical signal Depolarization opens voltage gate on VGCCs  Ca2+ influx Vesicles contain calcium sensor  trigger vesicle fusion with membrane (exocytosis) NTs flow down concentration gradient into synapse Neurotransmitters Neurotransmitter (NT) – endogenous chemical specialized for transmitting information between neurons • Endogenous – naturallyoccurring, originating from organism itself Receptors Receptor – protein that receives and transduces signals • Typically postsynaptic • Binding sites – areas dedicated to detecting/binding NTs NTs fit in receptors and activate them  postsynaptic effect Many receptors are simply ligand-gated ion channels Simplest receptors = ligandgated ion channels (called ionotropic receptors) • open in response to ligand binding • Very fast changes in Vm! • Effect depends on ion selectivity Clearing NTs from the synapse Degradation - rapid breakdown/inactivation of NT by an enzyme Reuptake - NT is reabsorbed by transporters in presynaptic terminal to be reused Diffusion – NT molecules diffuse out of the synapse Postsynaptic effects Postsynaptic potentials (PSPs) - brief changes in postsynaptic Vm • Small, local, graded potential • Can be excitatory (depolarizing) or inhibitory (hyperpolarizing) Postsynaptic potentials Excitatory postsynaptic potential (EPSP) – depolarizing PSP • Na+ channels • Pushes postsynaptic Vm toward the AP threshold Postsynaptic potentials Inhibitory postsynaptic potential (IPSP) hyperpolarizing PSP • K+ or Cl- channels • Pushes postsynaptic Vm away from threshold Signal integration Signal integration – how PSPs interact on the postsynaptic neuron to influence its firing Integration happens at the axon hillock  adjacent to AIS Can occur in three ways: • Spatial summation • Temporal summation • Cancellation Signal integration over space Spatial summation adding up of potentials from different locations across the neuron at the axon hillock. Signal integration over time Temporal summation – adding up of all potentials that reach the axon hillock based on time of arrival. Integration can also mean cancellation! EPSP-IPSP cancellation IPSP spatially coincides with an EPSP and partially or totally cancels it out Your action items (8/31) Tuesday lab: PRA1 – Radiolab: Revising the Fault Line is due the start of lab! Neuroanatomy test will be next week in lab (9/12 and 9/14) Lab To-Do: Study for Neuroanatomy Test, listen to Radiolab: The Fix and be ready to discuss • PRA2 due in lab week of 9/18 Coming Up: • Tuesday: The Chemistry of Behavior (Breedlove 3.3-3.4, 4.1-4.3) • Thursday: Drugs and Addiction (Breedlove 4.4-4.7) GBP opportunity!