Exam 2 - BN SMU The Synapse

demonstrated synapse and leg flexion reflex in dogs
inferred several properties through experiement on the reflex arc
3 major conclusions

communication between one neuron and the next differs from communication along a single axon → inferred a specialized gap between neurons

measurement of time between stimulation of skin and response of muscle

purely behavioral observation: strapped a dog into a harness above the ground and pinched one of the dog's feet. After a fraction of a second, the dog flexed (raised) the pinched leg and extended the other legs → found that spinal cord controlled the flexion and extension reflexes
he isolated the reflex arc from the brain because it works purely on the level of the spinal cord

speed of conduction through the reflex arc was slower than the known speed of conduction along an interrupted → concluded that some process must be slowing conduction through the reflex → inferred that delay was where one neuron communicates with another (at the synapse)

the speed of conduction along an axon is about 40 m/s
the speed of conduction through a reflex arc is slower and more variable, sometimes 15 m/s or less -> DELAY HAPPENS AT SYNAPSE

repeated stimuli occurring within a brief time are cumulative and produce a reflex

pinching the leg once does not evoke a reflex -> no response
pinching the several times in fast succession → movement
conclusion: the more rapid the pinching, the greater the movement

the neron that delivers transmission

the neuron that receives the transmission

several synaptic inputs originating from separate locations at the same time are cumulative and produce a reflex -> concluded that pinching 2 points activated separate sensory neurons, whose axons converged into one neuron in the spinal cord → combination of excitations exceeded threshold and produced action potential

Pinching leg in one place → no response
Pinching leg in 2 different places → movement

sherrington's student, confirmed his findings
Single neuron recordings: graded depolarizations of the postsynaptic membrane (EPSP)
stimuli produce graded depolarizations, or EPSPs, on the membrane

also known as a graded depolarization -> results from a flow of sodium ions into the neuron
if an EPSP does not cause the cell to reach its threshold, the depolarization decays quickly

results from a flow of sodium ions into the neuron

Repeated stimuli generated EPSPs sufficient to cross the threshold → creates an action potential

Several stimuli at different locations generate EPSPs sufficient to produce action potential

typically occur together in one neuron -> a neuron might receive input from several axons in close succession
integrating these inputs provides complexity

when the flexor muscle of stimulated leg contracted (lifted the leg), the extensor muscle relaxed
at the same time: extensor muscles of the other 3 legs contract (to maintain balance), connection through interneuron

temporary hyperpolarization of the membrane, occurs when synaptic input selectively opens the gates for potassium ions to leave the cell, chlorine enters the cell

occurs when synaptic input selectively opens the gates for potassium ions to leave the cell
Inflow of negatively charged chloride ions into the cell as well, not just the outflow of potassium cells

IPSP increase negative charge on membrane, decreasing the probability of an action potential

when flexor muscles contract, interneuron in spinal cord generates graded hyperpolarizations, or IPSPs on the neuron that controls the extensor muscles

During an EPSP, sodium gates open. During an IPSP, potassium or chloride gates open.

No. Only action potentials propagate along an axon. Inhibitory messages (IPSPs), decay over time and distance

Neurons may have thousands of synapses along their membrane, some generating EPSPs others IPSPs
some synapses produce fast, brief effects while others produce slow, long-lasting effects
Extremely complex wiring, endless possibilities

Summation not always exactly additive (effect of 2 can be more or less than double)
Any behavior is a function of many, many neurons and synapses with variable properties

most neurons have this, a periodic production of action potentials even without synaptic input (when its not stimulated)

increase the frequency of action potentials above the spontaneous rate -> increases rate of firing

decrease the frequency of action potentials above the spontaneous rate -> decreases rate of firing

if the neuron's spontaneous firing rate is 10 action potentials per second, a stream of EPSPs might increase the rate to 15 or more, while IPSPs might decrease it to 5 or fewer

found that applying the hormone adrenaline directly to the surface of the heart and other organs produces the same affects as those of the sympathetic nervous system -> he concluded that the sympathetic nerves stimulate muscles by releasing adrenaline or a similar chemical and that synapses use chemicals to link neurons
KEEP IN MIND: NOT DEFINITIVE

Demonstrated for the first time the chemical nature of impulse transmission between neurons (nerves send messages by releasing chemicals)
before that, there was a firm belief in electrical transmission

repeatedly stimulated the vagus nerve (part of the parasympathetic ns) of a frog -> decreased the frog's heart rate
then, he collected the fluid around the heart and transferred it to another frog's heart -> second heart also decreased heart rate

there is something in the fluid that regulates how the heart beats, in exactly the way the nervous system does

When he stimulated a nerve that increased or decreased a frog’s heart rate, he could withdraw fluid from the area around the heart, transfer it to another frog’s heart, and thereby increase or decrease its rate also.

- Synthesis
- Transport
- Release and diffusion
- Activation of receptors (ionotropic - metabotropic)
- Inactivation / reuptake
- Negative feedback to presynaptic terminal

chemical that is released by neuron at the synapse that stimulates another neuron (chemicals that affect another neuron)
has major classes

glutamate (excitatory), GABA (inhibitory)

neuropeptide Y, substance P, endorphins

widely distributed neurotransmitter

dopamine, epinephrine (adrenaline), serotonin

adenosine (metabolic activity, regulating sleep)

nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S)

dopamine, epinephrine, norepinephrine

Neurons synthesize neurotransmitters from amino acids in the diet (milk, eggs, meat, nuts, seeds)
EX: choline: for acetylcholine (if you eat liver there is a lot of it)
EX: phenylalanine: for catecholamines (soy foods)

Presynaptic terminal (in vesicles) → produces smaller neurotransmitters (ex: acetylcholine)
Cell body → produces larger neurotransmitters (ex: peptides)

storage for neurotransmitters in the presynaptic terminal
Exception is gases: they are released as they are produced

[an enzyme, MAO (monoamine oxidase) found in neurons that release serotonin, dopamine, or norepinephrine] breaks down transmitters into inactive chemicals -> prevents the transmitters from accumulating to harmful levels

Large neurotransmitters, after synthesis in cell body, are transported to various cell locations (travel down axon)

release requires repeated stimulation, mainly released by dendrites
not released often, but when they do, they release substantial amounts
diffuse widely, slowly affecting many neurons in their region of the brain
important for hunger, thirst, and other long-term changes in behavior and experience

They are not reabsorbed and recycled like smaller neurotransmitters → they are exhausted quickly
Often also released by dendrites, cell body, or axon
Stimulate neighboring dendrites to release same peptide

release from presynaptic terminal:
Action potential (depolarization) causes calcium channels to open → inflow of Ca2+ -> causes exocytosis
Release of neurotransmitters through membrane (exocytosis within 1-2 ms)
Diffuses into synaptic cleft in about 0.01 ms and attaches to a receptor

bursts of release of neurotransmitter from the presynaptic neuron
duration of 1-2 ms

NO - an action potential often fails to release any transmitter, and even when it does, the amount varies

Usually 2 or more neurotransmitters are released from each neuron: always the same combination
Advantage: interaction of transmitters allows for greater variation (fine tuning of response)

Neurons are not specific to just one neurotransmitter, they may receive and respond to many different ones

the effect of the neurotransmitter depends on its receptor on the postsynaptic cell
either produces ionotropic effect or metabotropic effect

a specialized protein embedded in the membrane
Forms a lock for which the neurotransmitter is the key

when the neurotransmitter binds to an ionotropic receptor, it twists the receptor just enough to open its central channel, which has a shape that lets a particular type of ion pass through
controlled by transmitter gated/ligand-gated channels (NOT VOLTAGE)
immediately opens gate -> effects begin quickly with short duration

Used for quick transmission like in vision, hearing, muscle movements because it is an immediate effect

at these receptors, neurotransmitters initiate a sequence of metabolic reactions that start slowly (30ms), but last longer than ionotropic effects
activates G-protein inside membrane -> G-protein then activates second messenger system
important for aspects of arousal, attention, pleasure, emotion (functions that arise more slowly and last longer than a visual or auditory stimulus)

When a neurotransmitter attaches to a metabotropic receptor, it bends the receptor protein that goes through the membrane of the cell → detaches G-protein so it can take its energy elsewhere in the cell → leads to increased concentration of a second messenger
just as the first messenger (the neurotransmitter) carries information to the postsynaptic cell, the second messenger communicates to areas within the cell

it may open or close ion channels in the membrane or activate a portion of a chromosome
Widespread effects typical for other senses (taste, smell, pain), attention, emotion

ionotropic synapse: has effects localized to one point on the membrane
metabotropic synapse: by way of the second messenger, influences activity in much or all of the cell and over a longer time

neurotransmitters don't just linger at the post synaptic membrane, various neurotransmitters are inactivited in different ways
neurotransmitter is broken down by enzyme and parts are taken back

after acetylcholine activates a receptor, acetylcholinesterase breaks it into 2 fragments: acetate and choline
the choline diffuses back into the presynaptic neuron and is then combined again with acetate already in the cell to form acetylcholine again

although the recycling process is efficient, it is sometimes not fast enough so the presynaptic neuron does not reabsorb every moleule it releases

the presynaptic neuron takes up much or most of the released neurotransmitter molecules intact and reuses them
neurotransmitters detach from the receptor, then are taken back up (often by membrane proteins called transporters)
any transmitter molecules that the transporters do not take are broken down by an enzyme called COMT -> breakdown products are washed away and eventually show up in blood and urine

common mechanism: inhibition of acetylcholine esterase → breakdown of acetylcholine in synaptic cleft → leads to overactivity at acetylcholine synapses
symptoms: small pupils, muscle spasms, vomiting excessive salivation
treated by anticholinergics

receptors that detect and respond to released transmitter quantities by inhibiting further synthesis and release
provide negative feedback to the presynaptic terminal

someone sends you an email and then, worried that you might not have received it, sends it again and again
to prevent cluttering your inbox, you add a system that provides an automatic answer; "yes i got you message, don't send it again"

some postsynaptic neurons respond to stimulation by releasing chemicals that travel back to the presynaptic terminal to inhibit further release of transmitter
ex: nitric oxide

Synapses are the major gateway for modulating our nervous system by drugs: all drugs that affect behavior act on synapses
Neurotransmitters effects on receptors mediate behavior such as learning, anxiety, and depression

asylums
straight jackets
ECT
psychosurgery -> lobotomies

not all synapses are chemical! a few special purpose synapses operate electrically when exact coordination is needed
because electrical transmission is faster than chemical transmission, electrical synapses have evolved in cases where exact synchrony between 2 cells is important (ex: cells that control rhythmic breathing)

at an electrical synapse, the membrane of one neuron comes into direct contact with the membrane of another
1. ion channels line up between presynaptic terminal and post-synaptic membrane
2. Free flow of ions (and thus depolarizations) between neurons
3. as a result, the two neurons act as if they were a single neuron

chemicals secreted by glands in one part of the body and transported by the blood to influence other organs
support basic functions: regulation of feedings, reproduction, wakefulness and sleep, mobilization of resources in stress
produced by endocrine glands → endocrine system
Coordinate long lasting changes

protein and peptide hormones, thyroid hormones, monoamines, steroid hormones

composed of chains of amino acids (proteins are longer, peptides are shorter)
bind to membrane receptors and activate second messengers within the cell (exactly like a metabotropic synapse)

increase metabolic rate, growth, maturation
contain iodine, such as thyroxine, from thyroid gland

effects similar to sympathetic nervous system; mobilization of organism for fight-flight
ex: epinephrine, norepinephrine; from adrenal gland (medulla)

secreted in stress, increase breakdown in fat and proteins into glucose
ex: cortisol, corticosterone; from adrenal gland (cortex)

neurotransmitters are like a telephone signal: conveys a message from the sender to the intended receiver
hormones are like a radio station: they convey a message to any receiver tuned to the right station

a network of glands and organs that produce hormones that regulate many of the body's functions
major glands:
pineal gland -> melatonin
pituitary gland -> adrenocorticotropic hormone (ACTH), oxytocin
adrenal gland -> cortisol, epinephrine
pancreas -> insulin, glucagon

"the master gland"; variety of hormones that control other glands, overall control by hypothalamus (attached to hypothalamus)
has 2 parts: anterior pituitary and posterior pituitary which release DIFFERENT sets of hormones

composed of neural tissue, can be seen as an extension of the hypothalamus
secretes hormones produced by the hypothalamus then releases them into the blood
neurons in the hypothalamus synthesize the hormones oxytocin and vasopressin, which migrate down axons to the posterior pituitary

hormone that constricts blood vessels, raises blood pressure; decreases urine volume

hormone that controls uterine contractions, milk release, parental behavior ("love hormone")

composed of glandular tissue
synthesizes hormones but controlled by releasing hormones from the hypothalamus
examples: ACTH and TSH

secreted by the hypothalamus, flow through the blood to the anterior pituitary
either stimulate or inhibit the release of other hormones

adrenocorticotropic hormone (ACTH): controls secretions of the adrenal cortex

thyroid-stimulating hormone (TSH): controls secretions of the thyroid

the hypothalamus maintains constant circulating levels of certain hormones through a negative feedback system

ex: when the level of thyroid hormone is low, the hypothalamus releases TSH- releasing hormone, which stimulates the anterior pituitary to release TSH -> causes the thyroid gland to secrete more thyroid hormones