Neurophysiology

Neurophysiology-                                                                         

Protons and electrons have electrical charge, and ions are atoms or molecules that bear a net charge because they have unequal numbers of protons and electrons.

-       Sodium: 11 protons, positive charge, 11 neutrons, 11 electrons, negative charge

-       Chlorine: 17 protons, 17 neutrons, 17 electrons, uncharged

o       Protons and neutrons in the nucleus

*Neurophysiology Lecture 1 Chem Review

Positively charged ions- Cations

-       Sodium

-       Potassium

-       Calcium

Negatively charged ions- Anions

-       Chloride

The movement or flow of charges makes up an electric current which is similar to the flow of water through pipes.

-       Take the ions and by moving their location, we can start to create an electrical current

-       Current is what neuron uses to transmit signal or message to another cell

When we separate positive and negative electrical charges, we call this Voltage or Potential difference

-       Extracellular

o       Outside of cell membrane has a more positive charge 

-       Intracellular

o       Inside of cell membrane has more negative charge

-       Extracellular

·       This gives us our voltage or potential difference

·       Goes all the way around the cell membrane

·       Happens on both sides of cellular membrane

·       The potential difference can do work when charges are allowed to flow as a current.

o       Able to have the energy to do work

o       When the energy current is flowing through the axon to transmit signal down the neuron

·       In our bodies the positive and negative charges are separated across cell membranes, and we call this the Transmembrane potential

§  because the inside is more negative than the outside, we say the transmembrane potential of a resting neuron (resting membrane potential) is –70 mV

-       Inside cell membrane on neuron, transmembrane potential is around -70mV, +- average, RESTING MEMBRANE POTENTIAL

-       -70 is resting membrane potential, it is when the neuron is at rest and not sending or transmitting any signals

·       What is responsible for the difference

§  Ions are distributed unequally

·       Sodium has a higher concentration on the outside of cell membrane than the inside

·       Potassium has a higher concentration on the inside than the outside

·       Chlorine/Chloride has a higher concentration in the inside rather than the outside of the cell

·       Extracellular cation (outside, positively charged) main one is SODIUM

·       Intracellular cation (inside), main one is POTASSIUM

·       Extracellular anion (outside), main one is CHLORIDE

§  inside the cell we also have negatively charged proteins

·       More negative inside of cell because there are more proteins

·       Proteins inside are also considered ions, negatively charged

§  cell membranes are semipermeable

·       Ions are separated and can only move through membrane through channels

·       Protein channels must be available for the sodium, potassium, and chloride to move through

·       Proteins will not move through because they are too large to fit through channels

Graph to show action potential:

-       Time (ms) on X-AXIS

-       Voltage (mV) on Y-AXIS

-       -70 mV (RMP) starting point

o       If something becomes more negative, it will go below the -70

o       More positive, go above -70,

·       More positive does not always mean its going to become a positive number, just means that the number is getting closer to 0

So what causes the ions to flow into or out of the cell if the membrane channels are open?

-       This is how we know sodium will move in one direction and potassium will move the other direction, if there are membrane channels available for them to move through

·       Chemical gradients

o       Based on concentration of ion

o       MOVE FROM HIGH TO LOW

o       Diffusion

o       Does not require energy for this part to happen

o       Ex.

·       Sodium higher concentration outside, lower concentration inside, so sodium will want to come through inside if channel is available and open

·       Potassium has a higher concentration inside, and a lower concentration on the outside, so if channel is open and available, potassium will wanna move out

·       Chloride has a higher concentration outside, lower concentration inside, chloride will wanna move from HIGH TO LOW, and go inside the cell

·       Electrical gradients

o       Because there’s a charge, we have to consider electrical gradients

o       At rest, outside has a more positive charge

o       At rest, inside has a more negative charge

o       Ex. OPPOSITES ATTRACT AS FAR AS ELECTRICAL CHARGES GO

·       Sodium, positively charged ion

·       Positively charged sodium, will be attracted to negatively charged inside of the cell, so move into cell

·       Potassium, positively charged ion, attracted to negative inside cell membrane, based on electrical charge potassium will want to move into cell as well, OPPOSITE OF ITS CHEMICAL GRADIENT

·       Chloride, negatively charged ion, will want to move out to positive side of cell membrane, OPPOSITE OF CHEMICAL GRADIENT

·       MOVEMENT IS BASED ON CHARGE, OPPOSITES ATTRACT

·       Pos charged > neg area

·       Neg charged > pos area

·       Electrochemical gradients

o       Both gradients together, determine the movement of this ion across the cell membrane

o       Sodium:

·       Chemical gradient: Sodium wants to move inside, low concentration area

·       Electrical gradient: Sodium wants to move inside, more negative area

·       Add together, both movements favor moving into the cell, so the electrochemical gradient will favor sodium moving in

·       Adding these two forces together creates a very large electrochemical gradient, where sodium moves into the cell

o       Potassium:

·       Chemical gradient: Potassium wants to move out of the cell, low concentration area

·       Electrical gradient: Potassium wants to move into cell, more negative area

·       Favoring movement of opposite directions

·       Electrochemical gradient will be WHICHEVER ONE HAS THE HIGHER VALUE

·       CHEMICAL GRADIENT has a HIGHER FORCE than the electrical gradient

·       Electrochemical gradient will favor potassium moving out, but they are going in opposite directions with the electrical and chemical gradient

·       Because of opposition and not full favor, there is a smaller force of electrochemical gradient

-       Equilibrium:

o       If we let these ions move by themselves until they reached equilibrium in a balanced direction back and forth

o       Sodium reaches equilibrium at a around +66mV

o       RMP is -70mV

o       Moves by 136 mV between -70 and +66

o       Sodium has a much larger electrochemical gradient that’s going to cause sodium to come into the cells versus potassium leaving the cell

o       Potassium would make the inside of the cell more negative, because it’s a positive ion moving out

o       Reaches equilibrium around -90mV, factor of 20

·                 Establishing the Resting Membrane Potential

·       To maintain RMP and return cells to RMP after a change in membrane potential

·       Sodium-potassium (Na⁺-K⁺) ATPase pump

·       FOUND ON ENTIRE PART OF NEURON

o       Moving sodium and potassium through the channel

o       ATPase pump, meaning that it uses ATP as an energy source to pump atoms/ions across cell membrane against concentration gradient, move against concentration gradient

o       Move 3 sodium ions out for every 2 potassium coming in

o       Job is to maintain RMP

o       Keeps RMP at -70 mV

o       After a change in the membrane potential, with greater and action potentials, sodium-potassium pump restores RMP by moving ions back to where they need to be (sodium, potassium)

o       Concentration gradients:

·       Sodium has a higher concentration gradient outside the cell, so sodium will move from low concentration inside to high concentration outside

·       Potassium has a higher concentration gradient inside the cell, so potassium will move from low concentration outside to high concentration inside

·       Opposites from each other

Membrane Channels that allow ion movement

·       Passive channels or leak channels

o   Channel is ALWAYS OPEN

o   Nothing that prohibits from something moving through channel

o   Potassium leak channels

o   Sodium leak channels

§  Both Present

o       Leak channels are found on dendrites, soma, axon, and terminals

·       Chemically regulated (ligand regulated) channels  

o   Chemically gated

o   Open or close in response to a specific chemical

o   Channel will have gate, if it binds to whatever neurotransmitter binds to it regularly, and that neurotransmitter binds to it, the channel will open

o   Ex. Sodium Channel

§  Sodium ions outside and inside and outside of cellular membrane, can’t move through channel when channel is closed, but when channel opens Sodium ions can move through and come inside cell

§  FOUND ON DENDRITES AND SOMA, NOT FOUND ON AXON OR TERMINALS

·       Mechanically regulated channels 

o   Open or close in response to a membrane distortion, Ex. Pressure, touch, vibration

o   Channels are closed, but if you touch your skin, the cells that receive the touch signals will change or distort cell membrane, and channels will pull open

o   Remove touch, channels will close

o   FOUND ONLY ON DENDRITES AND SOMA

·       Voltage regulated channels

o   Voltage gated 

o   Open or close in response to a change in the transmembrane potential

o   A change in voltage

o   Cell membrane has a volt charge already on it

o   When change, open or close results

o   FOUND ON AXON AND TERMINALS

Overview of neuron activity

Local Potentials or Graded Potentials 

When a neuron is stimulated by a signal from another neuron, a ligand binding to a chemical channel or a shape change in a mechanically regulated channel it causes small local disturbances in the membrane potential. These channels allow Na⁺ to flow into the cell.

-       Overall goal:

o       If we want neuron to create a single that goes down the length of that axon

o       We need to get the axon hillock to reach THRESHOLD, overall goal

o       RMP is at -70mV, THRESHOLD is at -60mV, little more positive

-       What happens:

o       Whatever that stimulus is, Stimulus source

o       Stimulus source: cell- cell releases a chemical

o       Chemical binds to sodium channel on soma

o       If chemically gated channel, channel will open and sodium ions outside will come into cell

o       Once sodium ions are in, we’ve brought a more positively charged ion into the cell

o       Charge inside cell membrane will flip

o       Inside cell membrane is gonna become more positively charged, will move closer to 0

Graph Ex.

-       Time (ms) on X-AXIS

-       Voltage (mV) on Y-AXIS

-       RMP -70mV, 0 above it

-       When membrane is at rest, before we do anything/anything occurs, we are sitting at -70mV

-       When we apply stimulus, sodium channels open, sodium comes into the cell and makes inside of cell more positive because they are positively charged ions and the cell is going to depolarize

-       When cell DEPOLARIZES we see cell become more positive/come closer to 0

-       At the peak, is when stimulus is removed, SPA (sodium potassium atpase) PUMP, always moving, will take sodium and put it back outside the cell

-       Brings cell back down to rest

-       Sodium channels open right at the start as we rise from RMP

-       Sodium channels close right at the peak when stimulus is removed

-       SPA PUMP removes the sodium from inside, and bring us back down toward rest

Ex.

-       Stimulus only opened, only enough neurotransmitter to open two channels, so we did depolarize the membrane, but not all the way

-       The goal is to get axon hillock to -60mV, but with the couple of channels open it was not enough to depolarize the entire membrane at the axon hillock 

-       Even though neuron was stimulated, it was not enough to reach towards axon hillock to get -60mV

-       Either need stronger stimulus to release more chemicals or more of the neurotransmitter so that more channels open

-       OR

-       There needs to be a stimulus closer towards axon hillock

-       Stronger stimulus = more sodium coming into cell, and will diffuse away from the source and flip charge

-       Gets more positive in charge all the way down to axon hillock, and then action potential can start

o      Depolarization

o       Incoming Na+ ions diffuse short distances from the initial site producing a current along the dendrite and cell body toward the axon hillock or trigger zone; local potential – short distance

o       Characteristics of a local potential

§       Graded

o       Strength varies in magnitude depending on the stimulus

o       We can either open more channels or open the channels for longer

o       As long as neurotransmitter is in that space and bound to those channels, the channels will stay open which means more sodium can come in

§       Decremental

o       Signal weakens the further it travels

o       Signal starts off really strong, but as it travels and gets further away from signal source, signal will get weaker 

o       Starts maybe at -20mv but gets weaker and goes down to -40mv so membrane cannot depolarize as much

o       Goal is to get to threshold, which is just enough

§       Reversible

o       If you remove stimulus, you stop the signal, which causes it to back to normal resting rate

§       Excitatory or inhibitory

o       Excitatory: depolarize (make more positive)

o   Open sodium channels = excitatory

o   Chance of depolarizing that membrane or threshold at the axon hillock

o   Ex. Graph

o   Time vs Voltage

o   -70mV starting at rest

o   Stimulus applied; membrane depolarized (graph rises)

o   Remove stimulus at top

o   Membrane is re polarized

o   More positive is depolarized

o   More negative is repolarizing, returning to rest

o    

o       Inhibitory: hyperpolarize (make more negative)

o   Open potassium channels = inhibitory

o   Ex. Graph

o   Time vs Voltage

o   -70mV starting at rest

o   Instead of opening up sodium, stimulus is applied and potassium channels open

o   Potassium electrochemical gradient is going to cause potassium to move out of the cell

o   When positive ion leaves the cell (potassium), the cell will become more negative, we remove positive ion, makes more negative cell inside

o   Graph goes down, stimulus is removed at bottom peak

o   SAP pump restores resting membrane potential

o   More negative than -70mV is called HYPER POLARIZATION

o   Why inhibitory?

o   Axon hillock needs to reach -60mV THRESHOLD, inside of membrane in axon hillock needs to become more positive

o   If we hyper polarize, we are moving further away from threshold, which is harder to reach threshold

o   This means that the impulse traveling down the axon will have a harder time to travel through, which means we inhibited that neuron

o      Na⁺-K⁺ ATPase pumps return cell to resting membrane potential – RepolarizatioN

§       ALWAYS WORKING

§       Brings back to rmp

Action Potential 

Neurons can generate an electrical signal or action potential. The ion channels that produce action potentials are voltage-gated channels, that is, their opening depends on the membrane potential.

·       Local potential at axon hillock increases until it rises to threshold

·       Neuron produces an action potential; voltage-regulated Na⁺ channels open; more and more Na⁺ gates open as Na⁺ enters the cell; K⁺ gates open more slowly when threshold is reached (rapid depolarization)

·       When 0mV is reached/passed, Na⁺ gates are; voltage peaks at approx. +35mV (0mV in some, +50mV in others)

·       K⁺ gates now fully open; K⁺ leaves the cell repolarizing the membrane; causing shift back to negative inside and positive outside

·       K⁺ channels remain open a little longer than the Na⁺ channels and more K⁺ leaves than Na⁺ came in causing a 1 or 2 mV overshot or hyperpolarization

·       Characteristics of action potentials

·       All or none rule

§  Have to reach threshold for an action potential to occur

§  If we reach threshold, an action potential will occur

§  If we do not, it won’t

·       No signal degradation

§  As we create action potentials along the length of the axon, those actin potentials remain the same strength all the way down

·       Irreversible

§  Once an action potential is started, removing the signal will not stop it from occurring

-       Axon hillock sits at rests at -70mV

-       Local potential causes axon hillock to become more positive towards threshold (-60mV)

-       Once threshold is reached, voltage gated sodium channels open, potassium channels open, but they are so slow to open, depolarization occurs as sodium comes in at +35mV

-       At +35mV voltage gated sodium channels close, voltage gated potassium channels are fully open

-       More pos = depolarization

-       Sodium stops coming into cell, but potassium channels are open so potassium leaves the cell, repoloraziation occurs

-       Takes time to close, goes past -70mV, around -90mV (HYPERPOLARIZATION), return back to rest using ATPase pump, restores RMP

Refractory Period- Impossible or Difficult to make another action potential on a membrane segment

·       During an action potential and a few msec after, it is difficult or impossible to stimulate to produce another action potential – Refractory period

·       Two phases of refractory period

o   Absolute refractory period

§  No matter what, we CANNOT generate another action potential

§  No matter how strong the signal or stimulus is, we can no longer generate another action potential

§  That part of membrane cannot generate another action potential

·       Because: from threshold to +35mV, all sodium channels are already open (ALL OR NONE PRINCIPLE), cannot create another action potential because we do not have more sodium channels to open, all already open

§  +35mV to -50mV the inactivation gate is closed and will not reopen, no matter what happens with signal, gate will not reopen

§  2 parts ^ threshold and -50mV

·       Relative refractory period

§  It is possible to generate another action potential, but it is going tor esquire a very strong stimulus to do so

§  May generate an action potential

§  Happens from the end of absolute refractory to rest

§  Sodium channels can be reopened, but we need tor each threshold again, -60mV

§  Potassium is leaving during this period and making the cell more negative

§  Cell membrane charge is already more negative

§  In order to make more positive, a very big change compared to that, which means lots of sodium has to come in to overcome how negative the cell membrane is

§  Potassium is leaving to make cell more negative, sodium needs to come in to make it more positive

§  Once we overshoot rest and are at the hyperpolarization stage, instead of threshold only being ten units away, it is instead 15-20 units away

§  NEEDS a lot of sodium ions and a change of a charge to get back up to threshold and reopen those channels

§  Can be done, just very difficult

* Sodium channels have two types of gates

·       Inside gate: inactivation gate

·       Outside gate: activation gate

·       Looks like an upside-down house, missing one side of roof at -70mV

o       Activation gate is closed

o       Inactivation gate is open

§     All sodium ions cannot come through gate to get inside channel

·       When channel reaches threshold at -60mV

o       Activation gate opens

o       Inactivation gate still open

§     Because both gates are open sodium can come into the cell

·       +35mV

o       Activation gate stays open

o       Inactivation gate closes

§     Sodium cannot come into the cell, because inactivation gate is now closed

§     Can now repolarize the membrane

·       -50mV or so

o       Return back to original state

o       Activation gate is closed

o       Inactivation gate is open

o       Process may be repeated

Signal propagation in nerve fibers

-       Once an AP is generated at axon hillock, will cause next part of cell membrane to continue to generate APs down the length of the axon all the way down to the terminals and out the collaterals

Unmyelinated fibers: (Continuous propagation) 

-       Does not have Schwann cells or Oligodendrocytes wrapping the axon

-       Occur: Action potential is created, and the inside of the membrane is becoming more positive

-       This charge/current is going to travel down the length of the axon, which means that the next segment to undergo an action potential, while this one undergoes repolarization

-       This repeats along the length of the entire axon

-       Current flows in both directions, but AP WILL ALWAYS GO TOWARDS THE TERMINALS, never back towards the soma

-       This is because the membrane prior to ongoing AP is going through absolute refractory, so AP cannot be sent backwards because we cannot depolarize that part of the membrane

Myelinated fibers (Saltatory propagation)- SKIPPING, which means parts of the membrane can be skipped for depolarization

-       Nodes of ranvier

-       Only location able to do AP is where there is a node, because the Schwann cells are covering up the other areas of the membrane 

-       So membrane channels underneath the Schwann cells even if they open, will not be able to let anything through because they are covered by the myelin sheath

-       Do not have to depolarize every part of the membrane, saltatory propagation is faster

Axon diameter and propagation speed

-       Myelinated is faster

-       Larger diameter axon is axon

-       3 axon types

o       Type A: Largest Diameter and Myelinated = Fastest, 440ft/sec

·       Found with sensory, balance, touch, pressure, body positioning, motor (skeletal muscles)

o       Type B: Medium Sized and Myelinated = 60ft/sec

o       Type C: Smallest and Unmyelinated = 3ft/sec

o       TYPE B AND C are found within sensory, temperature, touch, pain, and pressure, motor (smooth and cardiac muscle, everything that is not skeletal, adipose tissues and glands)

Review questions:

1.     What causes K⁺ to diffuse out of a resting cell? What attracts it into the cell?

2.     What happens to Na⁺ when a neuron is stimulated on its dendrite? Why does the movement of Na⁺ raise the voltage on the plasma membrane?

3.     How does the plasma membrane at the trigger zone differ from that on the soma? How does it resemble the membrane at a node of Ranvier?

4.     What makes an action potential rise to +35 mV? What makes it drop again after this peak?

5.     List four ways in which an action potential is different from a local potential.

6.     Explain why myelinated fibers conduct signals much faster than unmyelinated fibers.

7.     Hyperkalemia is an excess of potassium in the extracellular fluid. What effect would this have on the resting membrane potentials of the nervous system and on neural excitability?

8.     Suppose a poison were to slow down the Na⁺-K⁺ ATPase pumps of nerve cells.  How would this affect the resting membrane potentials of neurons? Would it make the neurons more excitable than normal, or make them more difficult to stimulate? Why?

Nervous System Lecture – Synapses and Information Processing OUTLINE        

*What happens at the end of the neuron, at the axon collaterals to the axon terminal, how message is sent across synapse/space between neuron and effector cell                     

Synapse – a specialized site of contact between two neurons or a neuron and an effector (gland or muscle) that allows one-way flow of neural impulses: From neuron to effector or another neuron

2 TYPES OF JUNCTIONS:

·       Neuromuscular junction

o       Neuron to muscle

o       Muscle is effector

o       Smooth, Skeletal, or Cardiac

·       Neuroglandular junction

o       Neuron to gland

o       Sweat gland

o       Salivary gland

*Pre-synaptic vs Post-synaptic

·       Ex. If two neurons are synapsing with each other and both lead to the effector cell, but only one is touching, the first neuron is the presynaptic neuron and the second is the postsynaptic neuron

·       Presynaptic: Neuron that is before that synapse

·       Postsynaptic: Neuron that comes after synapse

·       IS ADJUSTABLE DEPENDING ON SYNAPSES, there may be more than one synapse

·       Postsynaptic cell**

·       Synaptic bulb – tips of the presynaptic neuron that contain synaptic vesicles containing a neurotransmitter that will aid in signal transmission across the synaptic cleft (20-30nm in length)

-       Vesicles contain neurotransmitters

o       Smaller green dots are neurotransmitters released when the vesicles fuse with cell membrane release neurotransmitter via EXOCYTOSIS

o       Neurotransmitter = Chemical, binds to CHEMICALLY GATED CHANNELS

Neurotransmitters can have an excitatory or inhibitory effect on the postsynaptic cell

*Effect depends on the type of channel they are opening

Ex.

-       If excitatory, will open channels that cause depolarization event, which means sodium channels open

-       If inhibitory, will cause hyperpolarizaiton, will need to open up potassium or chloride channels

100 diff types of neurotransmitters some…

*Wether excitatory or inhibitory is not dependent on the neurotransmitter, but instead dependent on what receptor the neurotransmitter binds to

·       Examples include:

o       acetylcholine (ACh)*

·       Found in CNS and PNS

·       Can have excitatory or inhibitory effects

·       Ex.

·       If ACh binds to the heart, it will have an inhibitory effect.

·       Will slow down heart rate if ACh binds to heart

·       If bind to smooth muscles within the digestive system, ACh will speed up digestion, an EXCITATORY effect

·       Dependent on if binds to sodium channel or potassium or chloride channel?

·       ACh is released at the cholinergic synapse

o       norepinephrine (NE)*

·       Primarily found in PNS

·       Can be excitatory or inhibitory

·       Ex.

·       If binds to heart, will speed up hr = excitatory

·       If binds to smooth muscle within digestive system = inhibitory, slowing down digestion

·       Released from adrenergic synapse

o       dopamine

·       Found in the brain, CNS

·       E or I

·       Loss of dopamine associated with Parkinson’s

·       A lot of treatments are associated with dopamine levels elevated to regulate symptoms

o       serotonin

·       CNS

·       Low levels of serotonin can lead to emotions, like depression, attention span

·       A lot of medications associated with depression are around keep serotonin levels elevated or around in the brain longer before degraded

Synapse transmission – excitatory cholinergic synapse: Sodium channels and ACh, same thing happens with an excitatory adrenergic synapse

·       Action potential arrives at the synaptic knob; voltage-regulated Ca²⁺ channels in the synaptic membrane open

·       Ca²⁺ enters synaptic knob and triggers exocytosis of ACh

·       ACh diffuses across the cleft and binds chemically (ligand)-regulated Na⁺ channels; channels open allowing Na⁺ in = depolarize postsynaptic membrane 20ms

·       influx of Na⁺ produces a local potential that carries to the axon hillock and if strong enough will generate an action potential

**If a neuron is postsynaptic, and not cell, hopefully it is enough that could generate an action potential if it reaches down to that axon hillock again

Ex Notes from Drawing:

·       Presynaptic Neuron connecting to a Postsynaptic Effector Cell

·       Inside the neuron there are vesicles which stores neurotransmitter = ACh because cholinergic synapse

·       On membrane of synaptic bulbs, instead of voltage gated sodium and potassium channels, it will be voltage gated calcium channels

·       Because excitatory, effector cell will have sodium channels, since binding to neurotransmitter, will be chemically gated

·       Synapse = space between presynaptic neuron and postsynaptic neuron/cell

·       Action potential created down the axon will continue down the collaterals

·       Then membrane of synaptic knob is depolarized, this depolarization will open up the voltage gated calcium channels

·       Calcium that is outside the cell will move into cell

·       Calcium entering the cell is going to trigger exocytosis of ACh

·       Vesicles will fuse with cell membrane and release ACh

·       ACh will diffuse across the cleft and bind with chemically gated sodium channels

·       ACh will bind to channels, open up gates and sodium from outside of cell will come through and cause depolarization on membrane of cell to create the next signal

Synapse transmission – inhibitory GABA-ergic synapse: GABA NEUROTRANSMITTER ALWAYS INHIBITORY

-       GABA opens chloride channels instead of sodium channels

-       Chloride = inhibitory effect = hyperpolarization

-       Inhibitory: Instead of chemically gated sodium channels, they are chemically gated potassium or chloride channels

*We do not want signal to occur forever, we do need it to stop

Cessation of the synaptic signal- Stopping of the synaptic signal

While it is important to stimulate or inhibit the postsynaptic cell with a neurotransmitter, the stimulus must be turned off otherwise the effector will continue responding to the signal when it is inappropriate, and this can be life threatening

·       the presynaptic cell stops releasing the neurotransmitter- 1

o       if still releasing neurotransmitter, the signal will go on and on and on

·       the neurotransmitter is released from the membrane channel on the postsynaptic membrane and diffuses into the extracellular fluid

o       astrocytes may absorb it and return it to the neurons- a

·       astrocytes can bring neurotransmitter back into the synaptic bulb and return the neurotransmitter back, which means it is removed from the synaptic cleft/space

o       synaptic knob may reabsorb the neurotransmitter by endocytosis then break it down with an enzyme called monoamine oxidase (MAO)- b

·       instead of using Astrocytes, the neuron can also reabsorb the neurotransmitter back and then break it down

·       If able to do this, will be broken down by MAO

·       Typically seen with norepinephrine  

·       If want to break down neurotransmitter, need MAO enzyme

·       If want to have the neurotransmitter present longer in synapse, you can inhibit enzyme MAO

·       Medications can sometimes do this, called MAOIs

·       Problem: does work, but lots of implications

·       Does not work with a lot of other medications

o       some neurotransmitters, like ACh, are degraded in the synaptic cleft- c

·       break it down in the synaptic cleft

·       Need enzyme called acetylcholinesterase (AChE)- SPECIFIC ONLY FOR ACH

·       Ends in “ase” which means that is an enzyme

·       Will take ACh and break it down into two parts

·       Acetate, excreted (Get rid of)

·       Choline, reused

o       d-

·       other types of neurotransmitters

·       can be broken down in the liver

·       neurotransmitter will enter bloodstream through the liver, and the liver will break down and degrade/get rid of all of it

Neuromodulators

·       chemicals (small peptides) released by the synaptic bulb along with neurotransmitters that modify the effect of the neurotransmitter

·       modify the effect of a neurotransmitter

ways they can do this:

1:

-       bind to receptors

-       either on presynaptic or postsynaptic cell

-       stimulate the cell to increase or decrease the number of receptors

-       Ex.

o       On presynaptic cell

o       Can decrease the number of calcium receptors

o       Less likely to be stimulated or to release a lot of neurotransmitters

o       Reduce the amount of calcium that’s been released

o       Can also increase/decrease the number of chemically gated channels, like sodium channels

o       Less channels for the neurotransmitter to bind to

2:

-       Alter the rate of neurotransmitter synthesis or production of the neurotransmitter

-       Alter rate of reabsorption or breakdown of the neurotransmitter

2 types of neurotransmitters the neuromodulator would be are:

1.     Nitric oxide: learning and memory, important as a vasodilator (blood vessels bigger), by causing smooth muscle relaxation

2.     Endorphins: get released in times of pain, inhibits pain signals

o       Ex.

§     Runners high

§     Feel great and no pain during a marathon, because pain signals are being blocked by endorphins

§     Occurs after a traumatic injury, e.g. a car accident where the person feels okay afterwards, but maybe the next day after the endorphins wear off, they start to feel pain and tightness

How neurotransmitters and neuromodulators work 

·       compounds that have a direct effect on membrane potential

·       compounds that have an indirect effect on membrane potential 

·       lipid-soluble gases that exert their effects inside the cell 

Postsynaptic potentials 

·       graded potentials that develop in the postsynaptic membrane (local potentials)

o   excitatory postsynaptic potential (EPSP)

o   inhibitory postsynaptic potential (IPSP)

Summation

One neuron may receive input from thousands of other neurons. Some incoming signals may produce EPSPs and some may produce IPSPs. The neuron’s response depends on the additive effects of the EPSPs and IPSPs.

·       Temporal summation  – addition of stimuli in a short period of time at a single synapse

·       Spatial summation   – addition of EPSPs from multiple synapses

Summation of EPSPs and IPSPs 

Presynaptic Facilitation 

·       Facilitation is the process in which one neuron enhances the effect of another.

Presynaptic Inhibition 

Neural coding

Neural coding is the process the nervous system uses to convert this information into meaningful patterns of action potentials.

The qualitative information is carried by specific neurons

The quantitative information – the intensity of the stimulus – is encoded two ways: neuron thresholds and frequency of stimulation.

Review questions from the book

1.     Describe the five steps that occur between the arrival of an action potential at the synaptic knob and the beginning of a new action potential in the postsynaptic neuron.

2.     Contrast the actions of acetylcholine, GABA, and norepinephrine at their respective synapses.

3.     Describe three mechanisms to stop synaptic transmission.

4.     What is the function of neuromodulators? Compare and contrast neuromodulators and neurotransmitters.

5.     Why is a single EPSP insufficient to make a neuron fire?

6.     Contrast the two types of summation at a synapse.

7.     Describe how the nervous system communicates quantitative and qualitative information about stimuli.

8.     List the four types of neural circuits and describe their similarities and differences.

9.     The local anesthetics lidocaine (Xylocaine) and procaine (Novocaine) prevent voltage-gated Na⁺ channels from opening. Explain why this would block the conduction of pain signals in a sensory nerve.