Chapter 2 Lecture

Modified: 2023-08-31 1:43 PM CDST

Nervous transmission is an electrochemical process. Chapter 2 concentrates on the activity of the synapse.

Module2.1

The Concept of the Synapse

• Neurons communicate by transmitting chemicals at junctions, called “synapses”

  • The term was coined by Charles Scott Sherrington in 1906 to describe the specialized gap that existed between neurons

  • Sherrington’s discovery was a major feat of scientific reasoning (done behaviorally with dogs)

The Properties of Synapses (p.42)

• Sherrington

  • Investigated how neurons communicate with each other by studying reflexes (automatic muscular responses to stimuli) in a process known as a reflex arc.

  • He discovered that reflexes are mediated by the spinal cord (read p. 43 to see how)

  • I usually demonstrate the startle reflex in class by making an unexpected loud noise. Then, I do it over and over. The reflex only happens when the noise is unexpected. Can't do that online, sorry!

• Example

  • Leg flexion reflex: a sensory neuron excites a second neuron, which excites a motor neuron, which excites a muscle

The Relationship Among Sensory, Motor, and Intrinsic Neurons (p.42)

Notice that the sensory neurons ENTER the spinal cord on the dorsal (back) side and that the motor neurons EXIT the spinal cord on the ventral (stomach) side.

Three Important Points About Reflexes

• Sherrington’s observations

  • Reflexes are slower than conduction along an axon

  • Several weak stimuli present at slightly different times or slightly different locations produce a stronger reflex than a single stimulus

  • As one set of muscles becomes excited, another set relaxes

  • The reflex impulse is mediated at the spinal cord level (that's why you may be surprised to see your foot jerk at the doctor's office when your patellar reflex is tested)

Difference in the Speed of Conduction

• Sherrington found a difference in the speed of conduction in a reflex arc from previously measured action potentials

  • He believed the difference must be accounted for by the time it took for communication between neurons

  • Evidence validated the idea of the synapse (the delay was caused by the actions taking place at the synapse)

Sherrington’s Evidence for Synaptic Delay

• Before you go further check out this summary page: Integration

• Temporal Summation

• Sherrington observed that repeated stimuli over a short period of time produced a stronger response

• Thus, the idea of temporal summation

  • Repeated stimuli can have a cumulative effect and can produce a nerve impulse when a single stimuli is too weak.

  • Think of this as the postsynaptic neuron saying, "I'm not going to wake up the boss (e.g., the CNS) unless this is really important."

• Excitatory Postsynaptic Potential (EPSP)

  • Presynaptic neuron: neuron that delivers the synaptic transmission

  • Postsynaptic neuron: neuron that receives the message.

    • Note: these terms are relative to a particular synapse. As the impulse travels down a series of neurons then the postsynaptic neuron becomes the presynaptic neuron for the NEXT synapse

  • Excitatory postsynaptic potential (EPSP): graded depolarization that decays over time and space

    • The cumulative effect of EPSPs are the basis for temporal and spatial summation.

    • Think of an EPSP synapse as one that will make the nervous transmission CONTINUE

• Spatial Summation

  • Sherrington also noticed that several small stimuli in a similar location produced a reflex when a single stimuli did not

    • Thus, the idea of spatial summation.

    • Think of spatial summation as several presynaptic neurons delivering EPSPs at the same time. The postsynaptic neuron will now be more likely to fire (continue the nerve impulse) that if only one neuron had fired.

    • Synaptic input from several locations can have a cumulative effect and trigger a nerve impulse

    • Spatial summation is critical to brain functioning

    • Each neuron receives many incoming axons that frequently produce synchronized responses

    • Temporal summation and spatial summation ordinarily occur together

    • The order of a series of axons influences the results

    • Undergraduate Video of both types of summation (but imagine that during temporal summation the pencil is hitting the balloon with the same intensity)

Recordings From a Postsynaptic Neuron During Synaptic Activation (p. 44)

Notice the All-or-None activity at 3 and 4 above. Also notice the IPSP at 5 (see below for more about IPSPs)

Temporal and Spatial Summation (p. 44)

Notice the temporal summation at upper left and the spatial at bottom. The postsynaptic neuron analyzes those inputs and then produces an EPSP to the next neuron (on the right). Below, we'll look at a neuron receiving EPSPs and IPSPs simultaneously.

The Effects of Summation (p. 45)

Here's another "but wait, there's more" moment: look at the order of the summations above. When the EPSPs arrive as on the left, more depolarization takes place.

Inhibitory Synapses

Sherrington noticed that during the reflex that occurred, the leg of a dog that was pinched retracted while the other three legs were extended

Suggested that an interneuron in the spinal cord sent an excitatory message to the flexor muscles of one leg and an inhibitory message was sent to the other three legs

Antagonistic Muscles (p. 45)

Muscles are paired (flexors and extensors). Here, notice the global response to the right paw's contraction of the flexors (the remaining three paws extensors contract).

Inhibitory Postsynaptic Potential (IPSP)

• Thus, the idea of inhibitory postsynaptic potential (IPSP)—the temporary hyperpolarization of a membrane

  • Occurs when synaptic input selectively opens the gates for positively charged potassium ions to leave the cell, or negatively charged chloride ions to enter the cells

  • Serves as an active “brake” that suppresses excitation.

  • Basically, an IPSP put a stop to (inhibits) nerve conduction, but that still conveys information!

    Think of the following example from a typical western movie. Two cowpokes, surrounded by night, are listening to the distant drums. Then one says to the other, "Listen". The other replies, "I don't hear anything". The first answers, "I know." The drums have stopped, and that conveys information, does it not? So, excitation and inhibition have the property of vastly increasing the information capacity of the nervous system because a decrease or an increase in the rate of nerve conduction conveys information.

• Relationship Among EPSP, IPSP,
  and Action Potentials

  • Sherrington assumed that synapses produce on and off responses

  • Synapses vary enormously in their duration of effects

    • The effect of two synapses at the same time can be more than double the effect of either one, or less than double

A Possible Wiring Diagram for Synapses (p.47)

In the diagram above EPSPs are in green and IPSPs are in red. In this case transmission will occur at the dentrite. Notice that any given neuron will respond or not depending on the input it receives. Dennett labels this as "armies of idiots" meaning that our complex behavior is the result of billions of neurons firing or not firing in a complicated manner.

• Spontaneous Firing Rate

  • The periodic production of action potentials despite synaptic input

    • EPSPs increase the number of action potentials above the spontaneous firing rate

    • IPSPs decrease the number of action potentials below the spontaneous firing rate.

    • Meaning that all neurons "check themselves out" constantly

Click here for a summary of action WITHIN neurons and here for a summary of action BETWEEN neurons

The Discovery of Chemical Transmission at Synapses

German physiologist Otto Loewi

The first to convincingly demonstrate that communication across the synapse occurs via chemical means

Neurotransmitters: chemicals that travel across the synapse and allow communication between neurons

Chemical transmission predominates throughout the nervous system

Module 2.2 Chemical Events at the Synapse (p. 50)

• The great majority of synapses rely on chemical processes

• Otto Loewi’s experiment

• Found that stimulating one nerve released something that inhibited heart rate, and stimulating a different nerve released something that increased heart rate

• Realized that he was collecting and transferring chemicals, not loose electricity

Nerves Send Messages by
Releasing Chemicals

• The Sequence of Chemical Events at the Synapse

• The major sequence of events allowing  communication between neurons across the synapse

  • The neuron synthesizes chemicals that serve as neurotransmitters

  • Action potentials travel down the axon

  • Released molecules diffuse across the cleft, attach to receptors, and alter the activity of the postsynaptic neuron

  • The neurotransmitter molecules separate from their receptors

  • The neurotransmitters may be taken back into the presynaptic neuron for recycling or diffuse away

  • Some postsynaptic cells may send reverse messages to slow the release of further neurotransmitters by presynaptic cells

  • So, nerve conduction is an electro-chemical process

Some Major Events in Transmission at a Synapse (p. 51)

Types of Neurotransmitters (p. 52)

Table 2.1 Neurotransmitters (p. 52)

• Neurons synthesize neurotransmitters and other chemicals from substances provided by the diet

  • Acetylcholine synthesized from choline found in milk, eggs, and nuts

  • Tryptophan serves as a precursor for serotonin

  • Catecholamines contain a catechol group and an amine group (epinephrine, norepinephrine, and dopamine)

Pathways in the Synthesis of Transmitters (p. 53)

• Storage of Transmitters

  • Vesicles: tiny spherical packets located in the presynaptic terminal where neurotransmitters are held for release

  • MAO (monoamine oxidase): breaks down excess levels of some neurotransmitters

  • Exocytosis: bursts of release of neurotransmitter from the presynaptic terminal into the synaptic cleft

    • Triggered by an action potential

Anatomy of a Synapse (p. 53)

a) mouse synapse (electron micrograph), b) axon terminals at soma (electron micrograph)

• Release and Diffusion of Transmitters

  • Transmission across the synaptic cleft (20–30 nm wide) by a neurotransmitter takes fewer than 0.01 ms

  • Most individual neurons release at least two or more different kinds of neurotransmitters

  • Neurons may also respond to more types of neurotransmitters than they release

• Activating Receptors of the Postsynaptic Cell

  • The effect of a neurotransmitter depends on its receptor on the postsynaptic cell

  • Transmitter-gated or ligand-gated channels are controlled by a neurotransmitter

• Ionotropic Effects

  • Occurs when a neurotransmitter attaches to receptors and immediately opens ion channels

  • Most effects:

    • Occur very quickly (sometimes less than a millisecond after attaching) and are very short lasting

    • Rely on glutamate or GABA

The Acetylcholine Receptor (p. 54)

a) at rest, b) attached to receptor

• Metabotropic Effects and Second Messenger Systems (p. 55)

  • Occur when neurotransmitters attach to a receptor and initiate a sequence of slower and longer lasting metabolic reactions

  • Metabotropic synapses use many neurotransmitters such as dopamine, norepinephrine, serotonin, and sometimes glutamate and GABA

    • When neurotransmitters attach to a metabotropic receptor, it bends the receptor protein that goes through the membrane of the cell 

    • Bending allows a portion of the protein inside the neuron to react with other molecules

  • Metabotropic events include such behaviors as taste, smell, and pain

Sequence of Events at a Metabotropic Synapse (p. 55)

G-Proteins

• G-protein activation: coupled to guanosine triphosphate (GTP), an energy storing molecule

  • Increases the concentration of a “second-messenger”

  • The second messenger communicates to areas within the cell

  • May open or close ion channels, alter production of activating proteins, or activate chromosomes

Neuropeptides

• Metabotropic effects utilize a number of different neurotransmitters

• Neuropeptides are often called neuromodulators

  • Release requires repeated stimulation

  • Released peptides trigger other neurons to release same neuropeptide

  • Diffuse widely and affect many neurons via metabotropic receptors

Distinctive Features of Neuropeptides (p. 56)

Drugs That Act by Binding to Receptors (p. 56)

• Many hallucinogenic drugs distort perception

  • Chemically resemble serotonin in their molecular shape (e.g., LSD)

  • Stimulate serotonin type 2A receptors (5-HT2A) at inappropriate times or for longer duration than usual, thus causing their subjective effect

• Nicotine stimulates acetylcholine receptors

Opiate Drugs and Endorphins (p. 56)

• Opiates attach to specific receptors in the brain

• The brain produces certain neuropeptides now known as endorphins—a contraction of endogenous morphines

• Opiate drugs exert their effects by binding to the same receptors as endorphins

• Opioids are synthetic opiates

  • Powerful analgesics

  • Analgesia vs Anesthesia

    • Analgesic: drug or substance that lowers pain levels

    • Anesthetic: drug or substance that lowers: touch sensitivity, hot and cold sensitivity, and pain (Novocain or Xylocain)

    I once had a small tumor cut out of my right bicep as an outpatient. The surgeon injected my arm and picked up the scalpel. I said, "wait." But he said with xylocaine you won't feel a thing, it's fast acting. I watched as he made a 2.5" incision, fluid and blood came out, but I felt nothing.

• Inactivation and Reuptake of Neurotransmitters (p. 57)

• Neurotransmitters released into the synapse do not remain and are subject to either inactivation or reuptake

• During reuptake, the presynaptic neuron takes up most of the neurotransmitter molecules intact and reuses them

• Transporters are special membrane proteins that facilitate reuptake

• Inactivation and Reuptake of Neurotransmitters (p. 57)

  • Examples of inactivation and reuptake

    • Serotonin is taken back up into the presynaptic terminal

    • Acetylcholine is broken down by acetylcholinesterase into acetate and choline

      Curare

      ---

      Curare, a South American poison, has its effect because it inhibits the action of an enzyme, cholinesterase. The effects of curare are muscular and respiratory paralysis. You may infer then, that the voluntary muscles and the lungs are controlled by the neurotransmitter, acetylcholine, abbreviated ACh. Curare does not affect neurons that are not controlled by ACh. Curare kills by causing all of the neurons that control breathing to be stuck open. Many of the nerve agents that the allied armed forces were concerned about during the Gulf War work in a similar fashion to curare.

      The movie, "The Emerald Forest," a true story about a child abducted and raised by Brazilian Indians, contains a scene in which the child and his adoptive father go monkey hunting. They find a monkey, and carefully prepare a blowgun dart by dipping it in the curare, which they carry on a pouch around their necks. They shoot the monkey, and hit it on the foot; then they wait. As the poison takes effect, the monkey stiffens, then falls to the ground. The two hunters then walk up to the monkey and kill it. Presumably, the monkey is able to see them as they walk up and then hit it on the head.

      If care is taken to keep the lungs working by artificial means, then curare will not be fatal. Before the widespread use of anesthetics, curare was routinely used in surgery. Patients were kept alive by artificial lungs until the curare dose wore off. The curare was used not as anesthetic but as a means of immobilizing the patient while the surgery took place.

      ---

       

    • Excess dopamine is converted into inactive chemicals

    • COMT: enzymes that convert the excess into inactive chemicals

• Stimulant Drugs

  • Amphetamine and cocaine

    • Stimulate dopamine synapses by increasing the release of dopamine from the presynaptic terminal

  • Methylphenidate (Ritalin)

    • Also blocks the reuptake of dopamine but in a more gradual and more controlled rate

    • Often prescribed for people with ADD; unclear whether Ritalin use in childhood makes one more likely to abuse drugs as an adult

• Negative Feedback from the Postsynaptic Cell

  • Negative feedback in the brain is accomplished in two ways (see figure below)

    • Autoreceptors: receptors that detect the amount of transmitter released and inhibit further synthesis and release

    • Postsynaptic neurons: respond to stimulation by releasing chemicals that travel back to the presynaptic terminal where they inhibit further release

• Cannabinoids

  • The active chemicals in marijuana that bind to anandamide or 2-AG receptors on presynaptic neurons or GABA

  • When cannabinoids attach to these receptors, the presynaptic cell stops sending

  • In this way, the chemicals in marijuana decrease both excitatory and inhibitory messages from many neurons

Effects of Some Drugs at Dopamine Synapses (p. 58)

• Electrical Synapses

  • A few special-purpose synapses operate electrically

  • Faster (and different) than all chemical transmissions

  • Gap junction: the direct contact of the membrane of one neuron with the membrane of another

  • Depolarization occurs in both cells, resulting in the two neurons acting as if they were one

A Gap Junction for an Electrical Synapse (p. 59)

• Hormones

  • Chemicals secreted by a gland or other cells that is transported to other organs by the blood where it alters activity

  • Produced by endocrine glands

  • Important for triggering long-lasting changes in multiple parts of the body

  • Slower acting integrative system

    • Days (e.g., 28) to years (0 to 18)

Location of Some Major Endocrine Glands (p. 60)

A Selective List of Hormones (p. 60)

• Proteins and Peptides

  • Composed of chains of amino acids

    • Proteins are longer chains; amino acids are shorter

  • Attaches to membrane receptors where they activate second messenger systems

• The Pituitary Gland and the Hypothalamus

  • Attached to the hypothalamus and consists of two distinct glands (aka the “master gland”

    • Anterior pituitary: composed of glandular tissue

    • Hypothalamus secretes releasing and inhibiting hormones that control anterior pituitary

    • Posterior pituitary: composed of neural tissue

    • Hypothalamus produces oxytocin and vasopressin, which the posterior pituitary releases in response to neural signals

Location of the Hypothalamus and Pituitary Gland in the Human Brain (p. 61)

Pituitary Hormones (p. 61)

Negative Feedback in the Control of Thyroid Hormones (p. 61)

• Maintaining Hormonal Levels

  • The hypothalamus maintains a fairly constant circulating level of hormones through a negative-feedback system

    • Example: TSH-releasing hormone and thyroid hormone levels.

    • Example: (use the Back button to return here) Keeping the house warm. Here, the thermostat plays the role of the pituitary gland, and the furnace the role of an endocrine gland. Note how negative feedback keeps the temperature of the house within a narrow range. The pituitary accomplishes the same pattern.

    • Positive feedback also occurs in behavior, economics, and house fires. In positive feedback the response grows and grows until it crashes. Example (use the Back button to return here)

    • Behavior: think of a concert and an encore. We saw Fleetwood Mac in N. Little Rock a few years ago. No one clapped strongly at the the end and the band did not play an encore. The NEXT night in Los Angeles, during the encore, Christine McVie, emerged through a trapdoor in the floor, and played. As you might imagine, the crowd went wild (aka, positive feedback). Eventually, though, the band has to leave and the audience has to go home.

    • Economics: think of a fad, Beanie Babies, baseball cards, or stock prices. When everyone wants to get one of those items, the price goes up and up. At some point, people begin to realize they are paying too much and the price crashes.

    • House fires: This is why there are no positive feedback thermostats! That thermostat would only say "make it hotter." You see the results. The house burns down and slowly cools.

    • Oh, btw, human sexual behavior often exhibits positive feedback. I'll let you figure that out for yourselves. Suffice it to say, there will be a point where "enough" will be heard.

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