Chapter 3 Synapses

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Charles Scott Sherrington:

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: In 1906, he physiologically demonstrated that communication between one neuron and the next differs from communication along a single axon; coined the term synapse to describe the specialized gap that existed between neurons; conducted his research on reflexes

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Reflexes:

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automatic muscular responses to stimuli; in a leg flexion reflex a sensory neuron excites a second neuron, which in turn excites a motor neuron, which excites a muscle

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Reflex arc:

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the circuit from sensory neuron to muscle response

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Sherrington observed three points:

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- Reflexes are slower than conduction along an axon.
- Several weak stimuli presented at slightly different times or slightly different locations produces a stronger reflex than a single stimulus does.
- As one set of muscles relaxes, another set becomes excited.

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Speed of a reflex and delayed transmission at the synapse:

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- Sherrington observed 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

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Temporal summation:

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(summation over time) repeated stimuli within a brief time have a cumulative effect; repeated stimuli can have a cumulative effect and can produce a nerve impulse when a single stimuli is too weak; a light pinch of the dog's foot did not evoke a reflex, but a few rapidly repeated pinches did

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Postsynaptic neuron:

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the cell that receives the message

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Presynaptic neuron:

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the neuron that delivers the synaptic transmission

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Excitatory postsynaptic potential:

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a graded depolarization; occurs when sodium ions enter the cell; if is does not cause the cell to reach its threshold, the depolarization decays quickly; the cumulative effect of EPSPs are the basis for temporal and spatial summation

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Spatial summation:

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summation over space; synaptic inputs from separate locations combine their effects on a neuron; pinching two places at once; a combination of pinches exceeded threshold and produced an action potential

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Temporal vs spatial summation:

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Temporal summation is the combined effect of quickly repeated stimulation at a single synapse (location). Spatial summation is the combined effect of several nearly simultaneous stimulations at several synapses onto one neuron.

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Interneuron, intermediate neuron:

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Sherrington also noticed that during the reflex that occurred, the foot of a dog that was pinched retracted while the other three feet were extended.
He 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.

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Inhibitory postsynaptic potential:

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temporary hyperpolarization of the 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

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Sherrington's inference of inhibitory synapses:

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When a flexor muscle is excited, the probability of excitation decreases in the paired extensor muscle. Sherrington inferred that the interneuron that excited a motor neuron to the flexor muscle also inhibited a motor neuron connected to the extensor muscle.

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Spontaneous firing rate:

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refers to 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

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Otto Loewi:

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German physiologist; was the first to convincingly demonstrate that communication across the synapse occurs via chemical means (1920)

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Neurotransmitters:

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chemicals that travel across the synapse and allow communication between neurons

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Sequence of chemical events at a synapse: 1

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The neuron synthesizes chemicals that serve as neurotransmitters. It synthesizes the smaller neurotransmitters in the axon terminals and neuropeptides in the cell body.

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Sequence of chemical events at a synapse: 2

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The neuron transports the neuropeptides that were formed in the cell body to the axon terminals or to the dendrites. (Neuropeptides are released from multiple sites in the cell.)

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Sequence of chemical events at a synapse: 3

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Action potentials travel down the axon. At the presynaptic terminal, an action potential enables calcium to enter the cell. Calcium releases neurotransmitters from the terminals and into the synaptic cleft, the space between the presynaptic and postsynaptic neurons.

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Sequence of chemical events at a synapse: 4

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The released molecules diffuse across the cleft, attach to receptors, and alter the activity of the postsynaptic neuron.

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Sequence of chemical events at a synapse: 5

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The neurotransmitter molecules separate from their receptors. Depending on the neurotransmitter, it may be converted into inactive chemicals.

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Sequence of chemical events at a synapse: 6

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The neurotransmitter molecules may be taken back into the presynaptic neuron for recycling or may diffuse away

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Sequence of chemical events at a synapse: 7

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Some postsynaptic cells send reverse messages to control the further release of neurotransmitter by presynaptic cells.

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Major categories of neurotransmitters:

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Amino acids (NH2), Neuropeptides (chains of amino acids), Acetylcholine , Monoamines, Purines, Gases (nitric oxide)

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Acetylcholine

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neurotransmitter; similar to an amino acid, except the NH2 group has been replaced by an N(CH3)3 group; synthesized from choline found in milk, eggs, and nuts

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Neurotransmitters:

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at a synapse, one neuron releases chemicals that affect a second neuron -> these are neurotransmitters

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Nitric oxide:

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NO; a gas released by many small local neurons; many neurons contain an enzyme that can produce NO efficiently; nitric oxide can dilate nearby blood vessels -> increasing blood flow to that area of the brain

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Catecholamines:

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three closely related compounds: epinephrine, norepinephrine, & dopamine (all contain a catechol group and an amine group)

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Tryptophan:

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amino acid; precursor to serotonin; crosses the blood-brain barrier by a special transport system; serotonin levels rise after eating something rich in tryptophan (like soy)

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Small neurotransmitters:

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Smaller neurotransmitters are synthesized in the presynaptic terminal and held there for release; ie acetylcholine

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Large neurotransmitters:

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Larger neurotransmitters are synthesized in the cell body and transported down the axon; ie neuropeptides

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Vesicles:

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tiny spherical packets located in the presynaptic terminal where neurotransmitters are held for release; the presynaptic terminal also maintains much neurotransmitter outside the vesicles

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MAO:

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a chemical that breaks down excess levels of some neurotransmitters; neurons that release serotonin, dopamine, and norepinephrine contain this enzyme

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Exocytosis:

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refers to the excretion of the neurotransmitter from the presynaptic terminal into the synaptic cleft.
Triggered by an action potential arriving fro the axon.

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Neurotransmitter release:

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when an action potential reaches the end of an axon, the action potential itself does not release the neurotransmitter, rather, the depolarization opens voltage-dependent calcium gates in the presynaptic terminal; causes exocytosis. an action potential often fails to release any transmitter, and the amount varies

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After release:

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the neurotransmitter is released from the presynaptic cell and diffuses across to the postsynaptic membrane, where it attaches to a receptor (Transmission across the synaptic cleft by a neurotransmitter takes fewer than .01 microseconds)

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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.

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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.

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Proteins:

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tether neurons together and guide neurotransmitters to receptors

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Ionotropic effect:

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refers to when a neurotransmitter attaches to receptors and immediately opens ion channels; Most effects occur very quickly and are very short lasting.
Most ionotropic effects rely on glutamate or GABA.

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Metabotrophic effects:

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occur when neurotransmitters attach to a receptor and initiates a sequence of slower and longer lasting metabolic reactions.
Metabotropic events include such behaviors as hunger, fear, thirst, or anger.
When neurotransmitters attach to a metabotropic receptor, it bends the rest of the protein .
Bending allows a portion of the protein inside the neuron to react with other molecules

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G-protein:

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The portion inside the neuron activates a G-protein –one that is coupled to guanosine triphosphate (GTP), an energy storing molecule.
G-protein increases the concentration of a “second-messenger”

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Second messenger:

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communicates to areas within the cell; may open or close ion channels, alter production of activating proteins, or activate chromosomes

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Neuropeptides are often called neuromodulators (have several properties that separate them from other transmitters):

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Are released by cell bodies, dendrites, and sides of the axons; Release requires repeated stimulation; Released peptides trigger other neurons to release same neuropeptide; Diffuse widely and affect many neurons via metabotropic receptors

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Hormone:

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

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Endocrine glands:

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responsible for the production of hormones; hormones are important for triggering long-lasting changes in multiple parts of the body

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Protein hormones and peptide hormones:

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are composed of chains of amino acids and attach to membrane receptors where they activate second messenger systems; hormones secreted by the brain can control the release of other hormones

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Pituitary gland:

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is attached to the hypothalamus and consists of two distinct glands that each release a different set of hormones (anterior and posterior pituitary)

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Anterior pituitary:

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composed of glandular tissue and synthesizes six hormones

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Posterior pituitary:

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composed of neural tissue and can be considered an extension of the hypothalamus

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Oxytocin and vasopressin, antidiuretic hormones:

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Neurons in the hypothalamus synthesize these hormones, which migrate down axons to the posterior pituitary

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Releasing hormones:

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Secreted by hypothalamus; flow through the blood and stimulate the anterior pituitary to release a number of other hormones.

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The hypothalamus...

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maintains a fairly constant circulating level of hormones through a negative-feedback system.
Example : TSH- releasing hormone

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Inactivation:

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Neurotransmitters released into the synapse do not remain and are subject to either inactivation or reuptake; Some serotonin and catecholamine molecules are converted into inactive chemicals:
COMT and MAO are enzymes that convert catecholamine transmitters into inactive chemicals.

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Reuptake:

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refers to when the presynaptic neuron takes up most of the neurotransmitter molecules intact and reuses them; transporters are special membrane proteins that facilitate reuptake.
Example: Serotonin is taken back up into the presynaptic terminal. Acetylcholine is broken down by acetylcholinesterase into acetate and choline.

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Negative feedback:

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accomplished in two ways:
Autoreceptors are receptors that detect the amount of transmitter released and inhibit further synthesis and release.
Post synaptic neurons respond to stimulation by releasing chemicals that travel back to the presynaptic terminal where they inhibit further release.