(3) Neurophysiology: The generation, transmission and integration of neural signals

Neurophysiology

Neurophysiology

The study of electrical and chemical processes in neurons

Ion

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

Anion

 A negatively charged ion, such as a protein or chloride ion

Cation

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

Intracellular fluid

Also called cytoplasm. The watery solution found within cells.

Extracellular fluid

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

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

Resting membrane potential

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

Millivolt (mV)

A thousandth 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 a molecules of a substance to spread away from regions of high concentration to regions of low concentrations.)

Concentration gradient

Variation of the concentration of a substance within a region

Ion channel

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

Potassium ion (K⁺)

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

Selective permeability

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

Equilibrium

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

Sodium ion (Na⁺)

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

Sodium-potassium pump

The energetically expensive mechanism that pushes sodium ions out of a cell, and potassium ions in.

Electrostatic pressure

The propensity of charged molecules or ions to move toward areas with the opposite charge.

Nernst 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.

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.

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 (Ca²⁺)

A calcium atom that carries a double positive charge because it has lost two electrons.

Action potential

The propagated electrical message of a neuron that travels along the axon to the presynaptic axon terminals. (A very brief but large change in neuronal polarization that arise in the initial segment of the axon and are propagated at high speed along the axon's length.) Is actively propagated (or regenerated) down through the axon through ionic mechanisms.

Hyperpolarization

An increase in membrane potential (the interior of the neuron becomes even more negative relative to the outside).

Depolarization

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

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.

Threshold

The stimulus intensity that is just adequate to trigger an action potential.

All-or-none property

The fact that the amplitude of the action potential is independent of the magnitude of the stimulus. Either it (the action potential) fires at its full amplitude, or it doesn't fire at all.

Afterpotential

The positive or negative change in membrane potential that may follow an action potential. Is (also) related to the movement of ions in and out of the cell.

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.

Refractory

(Unresponsive). Referring to transiently inactivated or exhausted axonal membrane.

Absolute refractory phase

A brief period, immediately following the production of an action potential, of complete insensitivity to stimuli. Caused by the voltage-gated Na⁺ channels being unresponsive.

Relative refractory phase

A period, following the absolute refractory phase, of reduced sensitivity during which only strong stimulation produces an action potential. Caused by the flow of K⁺ ions out of the cell having temporarily hyperpolarized the neuron, resulting in a stronger stimulus to 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.

Patch clamping

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

Axon hillock

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

Conduction velocity

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

Node of Ranvier

A 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.

Channelopathy

A genetic abnormality of ion channels, causing a variety of symptoms amongst others seizure disorders, as well as heritable muscle diseases and certain types of cardiac ailments.

Tetrodotoxin (TTX)

A toxin from puffer fish ovaries that blocks the voltage-gated sodium channel, preventing action potential conduction. Causes paralysis and death (rapidly).

Saxitoxin (STX)

An animal toxin that blocks sodium channels when applied to the outer surface of the cell membrane. Causes paralysis and death (rapidly).

Batrachotoxin

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

Neurotransmitter

Also called synaptic transmitter, chemical transmitter, or simply transmitter. The chemical released from the presynaptic axon terminal that serves as the basis of communication between neurons.

Postsynaptic potential

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

Excitatory postsynaptic potential (EPSP)

 A depolarizing potential in the postsynaptic neuron that is caused by excitatory connections, resulting in the postsynaptic cell being pushed a little closer to threshold for an action potential. EPSPs increase the probability that the postsynaptic neuron will fire an action potential. The depolarization is a result of channels opening to let in cations (making the cell more positive).

Synaptic delay

The brief delay between the arrival of an action potential at the axon terminal and the creation of a postsynaptic potential. (Reflects the time needed for the neurotransmitter to be released and diffuse across the synapse.)

Inhibitory postsynaptic potential (IPSP)

 A hyperpolarizing potential in the postsynaptic neuron that is caused by inhibitory connections. IPSPs decrease the probability that the postsynaptic neuron will fire an action potential. Is usually a result from the opening of channels that permit chloride ions (Cl^-) to enter the cell - because Cl^- ions are much more concentrated outside the cell than inside, they rush into the cell, making it even more negative.

Chloride ion (Cl^–)

A chlorine atom that carries a negative charge because it has gained one electron.

Spatial summation

The summation at the axon hillock of postsynaptic potentials (EPSP and IPSP) from across the cell body. If this summation reaches threshold, an action potential is triggered.

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. Postsynaptic effects that are not absolutely simultaneous can be summed due to the postsynaptic potentials lasting a few milliseconds before fading away. The closer they are in time, the greater is the overlap and the more complete is the summation. (If for an example EPSPs arrive one right after the other, they sum and the postsynaptic cell eventually reaches threshold and produces and action potential. If too much time passes between EPSPs, each will fade away before the next occur, and the neuron will never fire).

Exocytosis

The process by which a synaptic vesicle fuses with the presynaptic terminal membrane to release neurotransmitter into the synaptic cleft. This is mediated by specialized long-chain proteins.

V-SNARE

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

T-SNARE

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

Synaptotagmin

A specialized protein that responds to calcium ions to trigger vesicular exocytosis.

Botulinum toxin

A toxin that cleaves SNAREs, disabling neurotransmitter release.

Tetanus toxin

A toxin that cleaves SNAREs, disabling neurotransmitter release.

Ligand

A substance that binds to receptor molecules, such as those at the surface of the cell. Results in teh receptor protein being activated or blocked.

Acetylcholine (ACh)

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

Receptor molecule

Also called receptor. A protein that binds and reacts to molecules of a neurotransmitter or hormone.

Endogenous ligand

Any substance that is produced within the body and selectively binds to the type of receptor that is under study. Examples of this are neurotransmitters and hormones.

Exogenous ligand

Any substance that originates outside the body and selectively binds to the type of receptor that is under study. Examples of this are drugs and toxins (from outside the body).

Curare

An alkaloid neurotoxin that causes paralysis by blocking acetylcholine receptors in muscle.

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. Examples hereof are muscarine and nicotine.

Antagonist

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

Cholinergic

 Referring to cells that use acetylcholine as their synaptic transmitter.

Up-regulation

A compensatory increase in receptor availability at the synapses of a neuron. (A process that increases receptor density)

Down-regulation

A compensatory reduction in receptor availability at the synapses of a neuron. (A process that decreases receptor density)

Ionotropic receptor

Also called ligand-gated ion channel and 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

Also called 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. Also referred to as G-protein-coupled receptors (GPCRs). Neurotransmitter binding this receptor activates a subunit of the G protein to either open up a nearby ion channel or trigger other biochemical reactions in 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. Sometimes the protein itself acts to open ion channels, but in other cases the protein activates other internal chemicals to affect ion channels.

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. Several different of this(x) amplify the effect of the first messenger (neurotransmitter) and can initiate processes that lead to changes in electrical potential at the membrane. An important feature of x-systems is their ability to amplify and prolong the synaptic signals that a neuron receives.

Degradation

The chemical breakdown of a neurotransmitter into inactive metabolites. (A process where a transmitter can be rapidly broken down and thus become inactivated by a special enzyme)

Reuptake

The process by which released synaptic transmitter molecules are taken up and reused by the presynaptic neuron, thus stopping synaptic activity. (A process where transmitter molecules might be rapidly cleared from the synaptic cleft by being taken up into the presynaptic terminal)

Transporter

A specialized receptor in the presynaptic membrane that recognizes transmitter molecules and returns them to the presynaptic neuron for reuse.

Autoreceptor

A receptor for a synaptic transmitter that is located in the presynaptic membrane, telling the axon terminal how much transmitter has been released.

Axo-dendritic

Referring to a synapse in which a presynaptic axon terminal synapses onto a dendrite of the postsynaptic neuron, either via a dendritic spine or directly onto the dendrite itself.

Axo-somatic

Referring to a synapse in which a presynaptic axon terminal synapses onto the cell body (soma) of the postsynaptic neuron.

Axo-axonic

Referring to a synapse in which a presynaptic axon terminal synapses onto another axon’s terminal. Allows the presynaptic neuron to regulate how much neurotransmitter will be released from the targeted terminal.

Dendro-dendritic

Referring to a synapse in which a synaptic connection forms between the dendrites of two neurons. Allows coordination of the dendrites of the two neurons activities.

Ectopic transmission

 Cell-cell communication based on release of neurotransmitter in regions outside traditional synapses.

Varicosity

The axonal swelling from which neurotransmitter diffuses in a nondirected synapse.

Nondirected synapse

A type of synapse in which the presynaptic and postsynaptic cells are not in close apposition; instead, neurotransmitter is released by axonal varicosities and diffuses away to affect wide regions of tissue.

Retrograde synapse

A synapse in which a signal (usually a gas neurotransmitter) flows from the postsynaptic neuron to the presynaptic neuron, thus counter to the usual direction of synaptic communication. By this, the postsynaptic neuron signals the presynaptic cell to release more transmitter

Electrical synapse

Also called gap junction. The region between neurons where the membranes are so close that changes in potential can flow from one to the other without being translated into a chemical message. Works with practically no time delay, in contrast to chemical synapses, where the delay is on the order of a millisecond (slow in terms of neurons). Frequently found in neural circuits that mediate escape behaviors in invertebrates and where many fibers must be activated synchronously, as in the system for moving our eyes. May contribute to the spread of synchronized seizure discharges in epilepsy.

Connexon

A protein assembly that provides an open ion channel between two neurons, forming an electrical synapse between them.

Neural chain

A simple kind of neural circuit in which neurons are attached linearly, end to end. Is routinely encountered in the nervous system.

Knee-jerk reflex

A variant of the stretch reflex in which stretching of the tendon below the knee leads to an upward kick of the leg.

Convergence

The phenomenon of neural connections in which many cells sends signals to a single cell

Divergence

The phenomenon of neural connections in which one cell sends signals to many other cells

Electroencephalogram (EEG)

A recording of gross electrical activity of the brain recorded from electrodes placed on the scalp

Epilepsy

A brain disorder marked by major sudden changes in the electrophysiological state of the brain that are referred to as seizures.

Seizure

An epileptic episode.

Tonic-clonic seizure

Formerly called grand mal seizure. A type of generalized epileptic seizure in which nerve cells fire in high-frequency bursts.

Simple partial seizure

 Also called absence attack. A seizure that is characterized by a spike-and-wave EEG and often involves a loss of awareness and inability to recall events surrounding the seizure.