Ch. 3: Neurophysiology

class: Biology Psychology

Neurophysiology

the study of electrical and chemical processes in neurons

• information flows within a neuron via electrical signals, while information passes between neurons through chemical signals

Ion

an atom or molecule that has acquired an electrical charge by gaining or losing one or more electrons

• electrically charged molecules

Anion

a negatively charged ion, such as a protein or sodium ion

• negatively charged ions

• EX: large protein anions

Cation

a positively charged ion, such as a potassium or sodium ion

• positively charged ions

Intracellular Fluid (Cytoplasm)

the watery solution found within cells

• where ions are dissolved

Extracellular Fluid

the fluid in the spaces between cells (interstitial fluid) and in the vascular system

• located near the cell membrane

Cell Membrane

the lipid bilayer that ensheathes a cell

Lipid Bilayer

the structure of the neuronal cell membrane, which consists of two layers of lipid molecules

Microelectrode

an especially small electrode used to record electrical potentials from living cells

• measure the difference in charge across the membrane

• gets inserted inside a neuron and using a voltmeter to compare the cell’s interior with the extracellular fluid surrounding it

Resting Membrane Potential

a difference in electrical potential across the membrane of a nerve cell during an inactive period

• a neuron’s is 50 to 80 thousandths of a volt

Millivolt (mV)

a thousandths of a volt

Negative Polarity

a negative electrical-potential difference relative to a reference electrode

Diffusion

the spontaneous spread of molecules of one substance among molecules of another substance until a uniform concentration is achieved

• the tendency of molecules of a substance to spread away from regions of high concentration to regions of low concentration

Concentration Gradient

variation of the concentration of a substance within a region

• molecules move until they’re evenly distributed

Ion Channels

a pore in the cell membrane that permits the passage of certain ions through the membrane when the channel is open

• tube-like pores

Potassium Ion

a potassium atom that carries a positive charge because it has one electron

• potassium ions can enter or exit the cell fairly freely, while other ions are impeded by the cell membrane

Selective Permeability

the property of a membrane that allows some substances to pass through, but not others

Equilibrium

the state in which the number of ions crossing a membrane in one direction is matched by the number crossing in the opposite direction

• every K+ ion pushed in one direction by diffusion would be matched by one pulled back by electrostatic charge

• electrostatic pressure and diffusion would be acting on ions in the immediate vicinity of the membrane and only a tiny fraction of the K+ ions would need to move to reach this equilibrium point of -58mV, so the concentration of ions would not significantly change on either side of the membrane

Sodium Ions

a sodium atom carries a positive charge because it has lost one electron

• much more concentrated outside neurons than inside because neurons use a sodium potassium pump mechanism

Sodium-Potassium Pump

the energetically expensive mechanism that pushes sodium ions out of a cell and potassium ions into a cell

• 3 Na- out for every K+ into the cell

• consumes energy

  • a large fraction of the energy consumed by the brain is used to maintain these ionic differences across neuronal membranes

• causes a buildup of K+ ions inside the cell

  • K+ ions will tend to leave the interior, down their gradient, causing a net buildup of negative charges inside the cell

Electrostatic Pressure

the propensity of charged molecules or ions to more toward areas with the opposite charge

• pulls K+ back inside the cell

• the concentration gradient pushing K+ ions out and the electrostatic pressure pulling them in cause the cell to reach K+ equilibrium and so any further movement of K+ ions into the cell (drawn by electrostatic pressure) is matched by the flow of K+ ions out of the cell (moving down the concentration gradient)

Nerst Equation

an equation predicting the equilibrium potential for a given ion based on the concentrations of the ion on opposite sides of a permeable membrane

• is permeable only to K+

Equilibrium Potential

the voltage across a permeable membrane that exactly counteracts the movement of ions from the side with a high concentration to the side with a low concentration

• the voltage difference across a permeable membrane needed to exactly counterbalance diffusion pushing an ion from the side of the membrane with a high concentration to the side with a low concentration

Goldman Equation

an equation predicting the potential difference across a membrane based on the concentrations of multiple ions on opposite sides of the membrane; as well as its relative permeability to each ion

Calcium Ion (Ca 2+)

a calcium atom that carries a double positive charge because it has lost 2 electrons

• neurons keep these levels low by intracellular ions low by using another ion pump to eject Ca2+ ions and by using specialized proteins that store Ca2+ to use for intracellular signaling, including the synaptic release of neurotransmitter

Action Potential

the propagated electrical message of a neuron that travels along the axon to the presynaptic axon terminals

• brief but large changes in neuronal polarization that arise in the initial segment of the axon and are propagated at high speed along the axon’s length

• the information that a neuron sends to its postsynaptic targets is encoded in patterns of these action potentials

• larger depolarizations produce more action potentials, not larger action potentials

  • the size/amplitude of of the action potential is independent of stimulus magnitude

Hyperpolarization

an increase in membrane potential (the interior of the neuron becomes even more negative)

• an increasing negativity of the membrane potential

  • EX: the neuron becomes more negative on the inside, relative to the outside

• produces an immediate response that passively follows the stimulus pulse

• Graded Response: the greater the stimulus, the greater the response, so the neuron’s change in potential

• as the potential spreads across the membrane, its size decays as a function of the square of the distance

Depolarization

a reduction in membrane potential (the interior of the neuron becomes less negative)

• a decreased polarization of the cell membrane

• makes the inside of the neuron more like the outside bringing its membrane potential closer to zero

Local Potential

an electrical potential that is initiated by stimulation at a specific site, which is a graded response that spreads passively across the cell membrane, decreasing in strength with time and distance

• graded and diminish over time and distance

• arise at synapses in response to other neurons

Threshold

the stimulus intensity that is just adequate to trigger an action potential

• -40mV

• a sudden and brief (0.5 to 2.0 millisecond) response

• the action potential is provoked

  • a rapid reversal of the membrane potential that momentarily makes the inside of the membrane positive with respect to the outside

  • Overshoot: the brief period when the neuron interior is positive

All-or-None Property

the fact that the amplitude of the action potential is independent of the magnitude of the stimulus

• either it fires at its full amplitude, or it doesn’t fire at all

• information is encolded by changes in the frequency of action potentials rather than in their amplitude

Voltage-Gated Na+ Channel

a Na+ selective channel that opens or closes in response to changes in the voltage of the local membrane potential; it mediates the action potential

• includes a tubular, membrane-spanning protein, but this NA+ selective pore is ordinarily closed

• when the cell membrane becomes depolarized to threshold levels, the channel’s shape changes, opening the pore to allow Na+ ions through

  • as long as the depolarization is below threshold, Na+ channels remain closed

  • when depolarization reaches threshold, a few Na+ channels open at first, allowing ions to start entering the neuron, depolarizing the membrane even further and opening still more Na+ channels

  • the process accelerates until the barriers are removed and Na+ ions rush in, both because they’re attracted to the negatively charged interior of the neuron and because they’re flowing down their concentration gradient

Afterpotential

the positive or negative change in membrane potential that may follow an action potential

• many axons exhibit electrical oscillations immediately following the spike

Refractory

referring to transiently inactivated or exhausted axonal membrane

• applying pairs of stimuli that are spaced closer and closer together reveals a related phenomenon: beyond a certain point, only the first stimulus is able to elicit an action potential

Absolute Refractory Phase

a brief period of complete insensitivity to stimuli

• phase one

• a brief period immediately following the production of an action potential, no amount of stimulation can induce another action potential, because the voltage-gated Na+ channels are unresponsive

Relative Refractory Phase

a period of reduced sensitivity during which only strong stimulation produces an action potential

• phase two

• only a very strong stimulation can produce another action potential, because the flow of K+ ions out has temporarily hyperpolarized the neuron, so a stronger stimulus would be needed to reach threshold

Voltage Clamping

the use of electrodes to inject current into an axon or neuron to keep the membrane potential at a set value

• the apparatus measures how much current must be injected to counteract any ion channel openings

• a stimulator is used to force the axon membrane to remain at a particular potential (voltage)

  • a voltmeter measures the potential difference between the 2 electrodes and sends that information to a voltage clamp amplifier, which compares the present membrane potential to a command voltage that the experimenter set

Patch Clumping

the use of voltage clamping to monitor current flow across a tiny patch of membrane taken from a cell

• pull away a tiny patch of membrane covering the microelectrode tip

Axon Hillock

a cone-shaped area from which the axon originates out of the cell body; the integration zone of the neuron

• the transmission of action potentials is limited to axons

• cell bodies and dendrites usually have few voltage-gated Na+ channels, so they don’t conduct action potentials

• is the slight welling of the axon where it emerges from the cell body where an axon potential starts

• can regenerate itself down the length of the axon

• 
  

Conduction Velocity

the speed at which an action potential is propagated along the length of an axon (or section of peripheral nerve)

• varies with the diameter of the axon

• larger axons allow the depolarization to spread faster through the interior

• myelin sheaths greatly speed up conduction

Nodes of Ranvier

a small gap between successive segments of the myelin sheath where the axon membrane is exposed

Saltatory Conduction

the form of conduction that is characteristic of myelinated axons, in which the action potential jumps from one node of Ranvier to the next

• because myelin insulation offers considerable resistance to the flow of ionic currents across the membrane, the action potential jumps from node to node

Channelopathies

a genetic abnormality in the form and function of ion channels, causing a variety of symptoms

Terodotoxin (TTX)

a toxin from puffer fish ovaries that blocks the voltage-gated sodium channel, preventing action potential conduction

Saxitoxin (STX)

an animal toxin that blocks sodium channels when applied to the outer surface of the cell membrane

Batrachotoxin

a toxin, secreted by poison arrow frogs, that selectively interferes with Na+ channels

Neurotransmitter (Synaptic/Chemical Transmitter)

the chemical released from the presynaptic axon terminal that serves as basis of communication between neurons

• the chemical signal that the electrical signal of the action potential gets converted into

Postsynaptic Potentials

a local potential that is initiated by stimulation at a synapse, can vary in amplitude, and spreads passively across the cell membrane, decreasing the strength with with and distance

• when integrated, this massive array of local potentials determines whether the neuron will reach threshold and therefore generate an action potential of its own

• excitatory and inhibitory neurons get their names from their actions on postsynaptic neurons, not from their effects on behavior

Excitatory Postsynaptic Potential (EPSP)

a depolarizing potential in the postsynaptic neuron that is caused by excitatory connections

• EPSPs increase the probability that the postsynaptic neuron will fire an action potential

• pushes the postsynaptic cell a little closer to the threshold for an action potential

• in the fastest cases, the postsynaptic depolarization begins about hald a millisecond after the action potential arrives at the presynaptic terminal

Synaptic Delay

the brief delay between the arrival of an action potential at the axon terminal and the creation of a postsynaptic potential

Inhibitory Postsynaptic Potential (IPSP)

a hyperpolarizing potential in the postsynaptic neuron that is caused by inhibitory connections

• decrease the probability that the postsynaptic neuron will fire an action potential

• hyperpolarization moves the cell membrane potential away from the threshold

• result from the opening of channels that permit Cl ions to enter the cell

  • Cl- is more concentrated outside the cell than inside the cell, so they rush into the cell making it more negative

Spatial Summaion

the summation at the axon hillock of postsynaptic potentials from across the cell body

• if this summation reaches threshold, an action potential is triggered

• the convergence of excitatory messages from many presynaptic neurons is required for a neuron to fire an action potential

Temporal Summation

the summation of postsynaptic potentials that reach the axon hillock at different times

• the closer in time the potentials occur, the more complete the summation

Steps in Transmission at a Chemical Synapse

• synaptic transmission: the transfer of information across a synapse

1. the action potential traveling down the axon arrives at the axon terminal

2. this depolarization opens voltage-gated calcium channels in the membrane of the axon terminal, allowing calcium ions (Ca2+) to enter the terminal

3. the Ca2+ causes synaptic vesicles filled with neurotransmitter to fuse with the presynaptic membrane and rupture, releasing the transmitter molecules into the synaptic cleft

4. transmitter molecules cross the cleft to bind to special receptor molecules in the postsynaptic membrane, leading to the opening of ion channels in the post-synaptic membrane

5. this ion flow creates a local EPSP or IPSP in the postsynaptic neuron

6. synaptic transmitter is either (a) inactivated (degraded) by enzymes or (b) removed from the synaptic cleft by transporters, so the transmission is brief and accurately reflects the activity of the presynaptic cell

7. synaptic transmitter may also activate presynaptic autoreceptors, regulating future transmitter release

• IPSPs and EPSPs in the postsynaptic cell spread throughout its interior

  • if it depolarizes the axon hillock enough, the post-synaptic neuron will fire an action potential of its own

  • the presynaptic terminal opens a voltage-gated calcium channels that allow an influx of Ca2+ ions into the axon terminal thus activating the enzymes that cause vesicles near the presynaptic membrane to fuse with the membrane and discharge their contents into the synaptic cleft

    • the higher the frequency of action potentials arriving at the terminal, the greater the influx of Ca2+, and the more vesicles that dump transmitter into the synapse

Exocytosis

the process by which a synaptic vesicle fuses with the presynaptic terminal membrane to release neurotransmitter into the synaptic cleft

v-SNARE

a specialized protein anchored to vesicles to aid their fusing to the presynaptic membrane to release neurotransmitter

• attached to the presynaptic membrane

t-SNARE

a specialized protein anchored to the presynaptic “target” membrane to bind v-SNAREs to dock vesicles, making them ready for release

• when the v-SNAREs attach,, the vesicle is said to be “docked”, ready to be released

Synaptotagim

a specialized protein that responds to calcium ions to trigger vesicular exocytosis

• a Ca2+ sensor

• when the action potential arrives at the axon terminal, the incoming Ca2+ ions bind and activate synaptotagmin, which then triggers the final fusion of the vesicular and presynaptic membranes, allowing the neurotransmitter molecules to enter the synaptic cleft

Botulinum Toxin (Botox)

a toxin that cleaves SNAREs, disabling neurotransmitter release by disabling exocytosis and synaptic transmission

Tetanus Toxin

a toxin that cleaves SNAREs, disabling neurotransmitter release by disabling exocytosis and synaptic transmission

Ligand

a substance that binds to receptor molecules, such as those at the surface of the cell

• can fit into a receptor protein and activate or block it

Acetylcholine (ACh)

a neurotransmitter produced and released by parasympathetic postganglionic neurons, by motor neurons, and by neurons throughout the brain

• can function as either an inhibitory or an excitatory neurotransmitter at different synapses

  • excitatory synapses: binding of ACh opens channels for Na+ and K+; ACh released onto muscle fibers excites them to contract

  • inhibitory synapses: ACh acts on a different type of receptor to open channels that allow Cl- to enter, thereby hyperpolarizing the membrane (i.e. making it more negative and so less likely to create an action potential)

Receptor Molecule (Receptors)

a protein that binds and reacts to molecules of a neurotransmitter or hormone

• ligand binding site

Endogenous Ligand

any substance that is produced within the body and selectively binds to the type of receptor that is under study

• neurotransmitters and hormones made inside the body

Exogenous Ligand

any substance that originates outside the body and selectively binds to the type of receptor that is under study

• drugs and toxins from outside the body

Curare

an alkaloid neurotoxin that causes paralysis by blocking acetylcholine receptors in muscle

• an arrowhead poison, extracted from a plant, that is used by indigenous South Americans

• if the hunter hits any part of the prey, the arrow’s poison soon blocks ACh receptors, paralyzing the animal

Bungarotoxin

a neurotoxin from the venom of the banded krait that selectively blocks acetylcholine receptors

Agonist

a molecule, usually a drug, that binds a receptor molecule and initiates a response like that of another molecule, usually a neurotransmitter

• act like a ransmitter at the receptor of that transmitter

• EX: nicotine; muscarine

Antagonist

a molecule, usually a drug, that interferes with or prevents the action of a transmitter

• interfere with or prevent the action of a transmitter

• EX: curare or bungarotoxin blocks the action of ACh

Cholinergic

referring to cells that use acetylcholine as their synaptic transmitter

• main subtypes: nicotinic and muscarinic

Up-Regulation

a compensatory increase in receptor availability at the synapses of a neuron

Down-Regulation

a compensatory increase in receptor availability at the synapses of a neuron

Ionotropic Receptor (Ligand/Chemically Gated Ion Channel)

a receptor protein that includes an ion channel that is opened when the receptor is bound by an agonist

Ligand-Gated Ion Channel (Chemically Gated Ion Channel)

an ion channel that opens or closes in response to the presence of a particular chemical

Metabotropic Receptor

a receptor protein that does not contain an ion channel but may, when activated, use a G protein system to alter the functioning of the postsynaptic cell

G proteins

a class of proteins that are next to the intracellular portion of a receptor and that are activated when the receptor binds an appropriate ligand on the extracellular surface

Second Messenger

a slow-acting substance in the postsynaptic cell that amplifies the effects of synaptic activity and signals synaptic activity within the postsynaptic cell