Chapter 5: How Neurons Communicate and Adapt Flashcards
who was the first to isolate a chemical messenger in their successful heartbeat experiment?
Otto Loewi
first neurotransmitter discovered in the PNS and CNS; activates skeletal muscles in the SNS; either excites or inhibits internal organs in the ANS
acetylcholine (ACh)
ACh can ___ skeletal muscles in the somatic nervous system and may ___ various internal organs in the autonomic system
excite; excite or inhibit
Loewi stimulated ___ to the heart, resulting in the heart rate increasing, and identified the chemical that carries the message to speed up heart rate in frogs as ___
the accelerator nerve; epinephrine
chemical messenger that acts as a neurotransmitter in the CNS and as a hormone to mobilize the body for fight or flight during times of stress (aka adrenaline)
epinephrine
___ and ___ are the same substance, produced by the adrenal glands located ___
adrenaline + epinephrine; atop the kidneys
in mammals, the chemical that accelerates heart rate is ___
norepinephrine
Loewi’s experiments show that acetylcholine from the vagus nerve ___ heartbeat, and epinephrine from the accelerator nerve ___ it
inhibits; excites
neurotransmitter that accelerates heart rate in mammals; found in the brain and in the sympathetic division of the ANS; aka noradrenaline
norepinephrine
chemical messengers released by a neuron onto a target to cause an excitatory or inhibitory effect
neurotransmitters
outside the CNS, many of the neurotransmitters circulate the bloodstream as ___
hormones
under the control of the hypothalamus, the ___ releases hormones into the bloodstream to excite/inhibit targets
pituitary gland
why are hormones slower than CNS neurotransmitters?
they have to travel larger distances to get to their receptors
the confirmed # of transmitters is ___, with most of the work being done by ___
60; 10
disorder of the motor system correlated w/ a loss of dopamine from the substantial nigra and characterized by tremors, muscular rigidity, and a reduction in voluntary movement
Parkinson disease
who found that, in Parkinson disease, the substantial nigra had degenerated?
Constantin Treatikoff
chemical examination of the brains of Parkinson patients showed that disease symptoms appear when the level of ___ was reduced to ___ of normal in the basal ganglia
dopamine; less than 10%
Urban Ungerstedt found that injecting a neurotoxin called ___ selectively destroyed the dopamine-containing neurons and produced symptoms of Parkinson disease
6-hydroxydopamine
loss of dopamine-containing substantia nigra neurons has been linked to environmental factors such as ___
insecticides, herbicides, fungicides, flu virus, toxic drugs
some Parkinson patients who receive dopaminergic drugs as therapy have become ___, despite showing no such tendencies before treatment
shopaholics or compulsive gamblers
membranous compartment that encloses a fixed number (quantum) of neurotransmitter molecules
synaptic vesicles
a. microtubule
b. mitochondrion
c. synaptic vesicle
d. storage granule
e. postsynaptic receptor
f. presynaptic membrane
g. synaptic cleft
h. postsynaptic membrane
i. neurotransmitter
j. channel
transport structure that carries substances to the axon terminal
microtubule
organelle that provides the cell with energy
mitochondrion
round granule that contains neurotransmitter
synaptic vesicle
large compartment that holds synaptic vesicles
storage granule
site to which a neurotransmitter molecule binds
postsynaptic receptor
encloses molecules that transmit chemical messages
presynaptic membrane
small space separating presynaptic terminal and postsynaptic dendritic spine
synaptic cleft
contains receptor molecules that receive chemical messages
postsynaptic membrane
how does the astrocyte surrounding the synapse contribute to chemical neurotransmission?
- supplying the building blocks for neurotransmitter synthesis
- confining the movement of neurotransmitters to the synapse
- mopping up excess neurotransmitter molecules
functional integration and physical proximity of the presynaptic membrane, postsynaptic membrane, and their intimate association w/ surrounding astrocytes
tripartite synapse
5 step process of neurotransmission
- the neurotransmitter is synthesized inside the neuron
- it’s packaged + stored within vesicles at the axon terminal
- it’s transported to the presynaptic membrane + released into the cleft in response to an action potential
- it binds to + activates receptors on the postsynaptic membrane
- it’s degraded or removed so it will not continue to interact w/ a receptor and work indefinitely
process that occurs when a neurotransmitter is released from a presynaptic neuron and binds to a receptor on the postsynaptic neuron
anterograde synaptic transmission
protein molecule that pumps substances across a membrane
transporter
___ transmitters are synthesized in the cell body, packed in membranes on the Golgi bodies, and transported on microtubules to the axon terminal
peptide
___ transmitters cannot be packaged/stored in vesicles, which are composed of lipids, but are rather synthesized “on demand” when an action potential reaches the axon terminal
lipid
___ transmitters are generated within the cells by enzymes, but they are able to permeate cell membranes and thus are not stored within the cell
gaseous
___ are not biochemically synthesized but are made in the hearts of dying stars, can be packed/stored in vesicles, and released into synaptic cleft
ion
neurotransmitters that are packaged into vesicles can be found at 3 locations at the axon terminal
- granules
- microfilaments
- presynaptic membrane
the presynaptic membrane is rich in ___ channels
voltage-activated Ca+ channels
3 steps of neurotransmitter release
- when an action potential reaches the voltage-sensitive terminal, it opens calcium channels
- incoming calcium ions bind to proteins, forming a complex
- this complex binds to vesicles, releasing some from filaments + inducing others to bind to the presynaptic membrane and to empty their contents by exocytosis
protein that has a binding site for a specific neurotransmitter and is embedded in the membrane of a cell
transmitter-activated receptors
embedded membrane protein; acts as
1. a binding site for a neurotransmitter
2. a pore that regulates ion flow to directly/rapidly change membrane voltage
ionotropic receptors
embedded membrane protein with a binding site for a neurotransmitter linked to a G protein; can affect other receptors or act with second messengers to affect other cellular processes, including opening a pore
metabotropic receptor
self-receptor in a neuronal membrane; that is, it responds to the same transmitter released by the neuron; part of a negative feedback loop allowing the neuron to adjust its output
autoreceptors
who concluded that the smallest postsynaptic potential is produced by the release of the contents of just 1 synaptic vesicle?
Bernard Katz
of neurotransmitter molecules, equivalent to the content of a single synaptic vesicle, that produces a just-observable change in postsynaptic electric potential
quantum
the # of quanta released from the presynaptic membrane in response to a single action potential depends on:
- the amt of Ca+ that enters the axon terminal in response to the action potential
- the # of vesicles docked at the membrane, waiting to be released
neurotransmitter inactivation can happen in 4 ways:
- diffusion
- degradation
- reuptake
- astrocyte uptake
7 types of synapses
- dendrodendritic
- axodendritic
- axoectracellular
- axosomatic
- axosynaptic
- axoaxonic
- axosecretory
dendrites send messages to other dendrites
dendrodendritic
axon terminal of one neuron synapses on dendritic spine of another
axodendritic
terminal with no specific target - secretes transmitter into extracellular fluid
axoextracellular
axon terminal ends on cell body
axosomatic
axon terminal ends on another terminal
axosynaptic
axon terminal ends on another axon
axoaxonic
axon terminal ends on tiny blood vessel and secretes transmitter directly into blood
axosecretory
which type of synapse is the most common in mammalian nervous systems?
chemical
area of contact between adjacent cells in which connexin proteins in each cell form connecting hemichannels, which, when open, allow ions to pass between the two cells (aka electrical synapse)
gap junction
gap junction
electrical synapses are ___ than chemical
faster
gap junctions allow ___ to exchange substances
glial cells + neurons
large biomolecules such as ___ cannot fit thru gap junctions
nucleic acids + proteins
gap junctions at axon terminal synapsing on dendrites and cell bodies allow for ___ transmission
dual chemical + electrical
why do mammals rely on chemical synapses more than gap junctions?
chemical synapses = plasticity, they can amplify/diminish a signal, and change with experience, mediating learning
gap junctions = speed + efficiency
neurotransmitters themselves do not determine excitation/inhibition, but ___ make the call
the ion channel associated w/ the receptor
- large active zone
- wide cleft
- dense material on membranes
- round vesicles
excitatory synapse
- small active zones
- narrow cleft
- sparse material on membranes
- flat vesicles
inhibitory synapse
the differing locations of excitatory and inhibitory synapses:
excitatory = dendritic tree
inhibitory = cell body/soma
the exocytosis mechanism for digestion in a single-celled organism is parallel to the ___ for communication in more complex creatures
release of a neurotransmitter
ionotropic receptor
metabotropic receptor
4 criteria for identifying neurotransmitters
- the transmitter must be synthesized in the neuron or otherwise be present in it
- when the neuron is active, the transmitter must be released and produce a response in some target
- the same response must be obtained when the transmitter is experimentally placed on the target
- a mechanism must exist for removing the transmitter from its site of action after its work is done
a suspect chemical that has not yet been shown to meet all the neurotransmitter criteria
putative transmitter
why is identifying chemical transmitters in the CNS hard?
there are thousands of synapses packed around every neuron, preventing easy access to a single synapse + its activities
all motor neuron axons leaving the spinal cord use ___ as a transmitter
acetylcholine
explain the Renshaw loop
- each axon has an axon collateral within the spinal cord synapses on a nearby CNS interneuron
- this interneuron synapses on the motor neuron’s cell body
what enables a motor neuron to inhibit itself from overexcitation?
the Renshaw loop
today, the term neurotransmitter applies to chemicals that:
- carry a message from the presynaptic membrane of one neuron to another by influencing postsynaptic membrane voltage
- change the structure of a synapse
- communicate by sending messages in the opposite direction
5 classes of neurotransmitters:
- small-molecule
- peptide
- lipid
- gaseous
- ion
quick-acting neurotransmitter synthesized in the axon terminal from products derived from the diet
small-molecule transmitters
how do small-molecule transmitters work?
- synthesized from dietary nutrients + packaged ready for use in axon terminals
- after released from a terminal button, it is quickly replaced at the presynaptic membrane
many neuroactive drugs are designed to reach the brain by the same route that ___ transmitters follow - the digestive tract
small-molecule
ACh molecules are synthesized from ___ by 2 enzymes, then broken down
choline + acetate
acetylcholine synthesis
- acetyl CoA carries acetate to the transmitter synthesis site
- ChAT transfers acetate to choline to form ACh
any chemical in limited supply that restricts the pace at which another chemical can be synthesized
rate-limiting factor
amine synthesis
tyrosine -> L-Dopa -> dopamine -> norepinephrine -> epinephrine
what enzyme is the rate-limiting factor in the production of dopamine, norepinephrine, and epinephrine?
the 2nd enzyme tyrosine hydroxylase
which neurologist administered L-dopa to a patient with Parkinson disease?
Oliver Sacks
by increasing the amount of dopamine in remaining synapses, L-dopa relieved the symptoms of ____
Parkinson disease
serotonin is synthesized from the amino acid ___
L-tryptophan
amine neurotransmitter; helps to regulate mood + aggression, appetite + arousal, perception of pain, and respiration
serotonin
amino acid neurotransmitter; typically excites neurons
glutamate (Glu)
amino acid neurotransmitter; typically inhibits neurons
gamma-aminobutyric acid (GABA)
structural difference between glutamate and GABA
they are the same except GABA does not have a carboxyl group on the bottom
glutamate is widely distributed in CNS neurons, but it becomes a neurotransmitter only if it is ___
appropriately packaged in vesicles at the axon terminal
___ is a much more common inhibitory transmitter in the brainstem and spinal cord, where it acts within the Renshaw loop
glycine (amino acid transmitter)
neurotransmitter that controls arousal + waking; can cause the constriction of smooth muscles; when activated in allergic reactions, constricts airway + contributes to asthma
histamine
histidine is converted by the enzyme ___ into histamine
histidine decarboxylase
the purine ___ consists of a molecule of adenine attached to a ribose sugar molecule and 3 phosphate groups
adenosine triphosphate (ATP)
a molecule that plays a central role in promoting sleep, suppressing arousal, + regulating blood flow to various organs thru vasodilation
adenosine
short, multifunctional amino acid chain (fewer than 100); acts as a neurotransmitter + can act as a hormone; may contribute to learning
neuropeptides/peptide transmitters
the process of neuropeptide synthesis/transport is relatively ___ compared to small-molecule neurotransmitters
slow
neuropeptides perform an enormous range of functions in the nervous system, acting as hormones that:
- respond to stress
- enable a mother to bond with her infant
- regulate eating + drinking, pleasure + pain
- contribute to learning
opium, morphine + related synthetic chemicals like heroin mimic the actions of endogenous brain opioid neuropeptides:
enkephalins, dynorphins, endorphins
___, released in response to exercise (runner’s high), has many times the analgesic potency of morphine
beta-endorphin
unlike many transmitters that bind to receptors associated w/ ion channel, neuropeptides are ___ and have no direct effects on ___
metabotropic; postsynaptic membrane voltage
peptide transmitters activate ___ that indirectly influence ___
synaptic receptors; cell structure + function
why can’t neuropeptides be taken orally as drugs like small-molecule transmitters?
digestive processes degrade neuropeptide amino acid chains
class of lipid neurotransmitters, including anandamide + 2-AG, synthesized at the postsynaptic membrane to act on receptors at the presynaptic membrane; affects appetite, pain, sleep, mood, memory, anxiety, and stress response
endocannabinoids
___ is the target of all cannabinoids, and are found at ___
CB1 receptors; both the glutamate and GABA synapses
___ act as neuromodulator to inhibit release of glutamate and GABA, thus dampening ___
cannabinoids; neuronal excitation/inhibition
3 gaseous neurotransmitters
- nitric oxide (NO)
- carbon monoxide (CO)
- hydrogen sulfide (H2S)
how do gaseous transmitters work?
- cells synthesize them on demand
- gas diffuses away, easily crossing cell membrane, immediately becoming active
gaseous neurotransmitter; acts to dilate blood vessels, aid digestion, & activate cellular metabolism
nitric oxide (NO)
gaseous neurotransmitter; activates cellular metabolism
carbon monoxide (CO)
gaseous neurotransmitter; slows cellular metabolism by preventing oxygen from binding in the mitochondria
hydrogen sulfide (H2S)
2 parts of an ionotropic receptor
- a binding site for a neurotransmitter
- a pore/channel
how does an ionotropic receptor work?
- neurotransmitter attaches to binding site
- receptor quickly changes shape, either opening the pore or closing it
ionotropic receptors are usually ___ because ___
excitatory; they bring about rapid changes in membrane voltage
ionotropic receptor
how does a metabotropic receptor work?
- transmitter binds to receptor
- triggers activation of a G protein
- affects ion channels or cells metabolic activity
metabotropic receptor
guanyl nucleotide-binding protein couples to a metabotropic receptor; binds to other proteins when activated
G protein
3 subunits of G protein
alpha, beta, gamma
what does the alpha subunit do on a G protein?
- detaches when a neurotransmitter binds to G protein’s receptor
- detached subunit can bind to other proteins within cell membrane or intracellular fluid
what happens when an alpha subunit binds to a nearby ion channel?
the channel structure changes, modifying the flow of ions (open/close) - this influences membrane’s electric potential
what happens when an alpha subunit binds to an enzyme?
second messenger is activated
metabotropic receptors allow for the possibility that a single neurotransmitter’s binding to a receptor can activate an escalating sequence of events called ___
an amplification cascade
the amplification cascade effect results in ___
many downstream proteins (second messengers, channels or both) being either activated or deactivated
ACh has an excitatory effect on skeletal muscles, where it activates an ___ receptor, and an inhibitory effect on heart rate, where it activates a ___ receptor
ionotropic; metabotropic
how is there variety of small-molecule neurotransmitter receptor subtypes?
alternative forms of each subunit can assemble in unique combinations to make a functional receptor
why does the brain contain so many receptor types for each neurotransmitter?
each subtype has slightly different properties which confer different activities
can different transmitters coexist in the same terminal or synapse?
yes
neurons that use acetylcholine as its main neurotransmitter
cholinergic neurons
at a skeletal muscle, cholinergic neurons are ___
excitatory, producing muscle contractions
the main transmitter-activated ionotropic channel receptor
nicotinic acetylcholine receptor (nAChr)
what happens when ACh or nicotine binds to the nAChr?
the pore opens, allowing simultaneous efflux of K+ and influx of Na+, depolarizing the muscle fibre
cholinergic neurons in the CNS synapse with ___ to prepare the body’s organs for fight or flight
sympathetic norepinephrine (NE) neurons
cholinergic neurons in the CNS synapse with ___ to prepare the body’s organs for rest and digest
parasympathetic acetylcholine (ACh) neurons
norepinephrine (NE) receptors on the ___ are excitatory, while NE receptors on the ___ are inhibitory
heart; gut
acetylcholine (ACh) receptors on the ___ are excitatory, while ACh receptors on the ___ are inhibitory
gut; heart
the ENS uses over __ neurotransmitters that are identical to those in the CNS
30
the 2 main small-molecule transmitters used by the ENS are:
serotonin + dopamine
neural pathways that coordinate brain activity thru a single neurotransmitter; its cell bodies lie in a brainstem nucleus; axons are distributed thru a wide CNS region
activating systems
the 4 activating systems
- cholinergic
- dopaminergic
- noradrenergic
- serotonergic
- active in maintaining attention + waking EEG pattern
- plays a role in memory by maintaining neuron excitability
- death of these neurons and decrease in this neurotransmitter in the neocortex are related to Alzheimer disease
cholinergic system (acetylcholine)
- this transmitter release causes repetition of behaviours
- the neurotransmitter system most affected by addictive drugs + behaviours
- increases in this transmitter activity may be related to schizophrenia
- decreases in this transmitter activity may be related to deficits of attention
mesolimbic pathways of the dopaminergic system
- active in maintaining normal motor behaviour
- loss of this neurotransmitter is related to muscle rigidity + dyskinesia in Parkinson disease
nigrostriatal pathways of the dopaminergic system
- active in maintaining emotional tone
- decreases in its neurotransmitter activity are related to depression
- increases in its neurotransmitter are related to mania
- decreased neurotransmitter activity is associated with hyperactivity and ADHD
noradrenergic system (norepinephrine)
- active in maintaining waking EEG pattern
- changes in its neurotransmitter activity are related to OCD, tics and schizophrenia
- decreases in its neurotransmitter activity are related to depression
- abnormalities in brainstem 5-HT neurons are linked to disorders like sleep apnea and SIDS (sudden infant death syndrome)
serotonergic system (serotonin)
in a rat brain, AChE permeates the cortex and is especially dense in the ___
basal ganglia
2 treatment strategies for Alzheimer disease
drugs that either
- inhibit enzyme acetylcholinesterase (raises levels of ACh)
- raise the # of nicotinic receptors
how can Parkinson disease be triggered by the ingestion of certain toxic drugs?
the drugs may act as selective neurotoxins that specifically kill dopamine neurons in the substantia nigra
how many people does Parkinson disease affect?
20 per 100,000
behavioural disorder characterized by delusions, hallucinations, disorganized speech, blunted emotion, agitation or immobility, + a host of associated symptoms
schizophrenia
how many people does schizophrenia affect?
1 in 100
mood disorder characterized by prolonged feelings of worthlessness and guilt, disruption of normal eating habits, insomnia, a general slowing of behaviour, frequent thoughts of suicide
major depression
disordered mental state of extreme excitement
mania
behaviour characterized by compulsively repeated acts and repetitive, often unpleasant, thoughts
obsessive-compulsive disorder (OCD)
___ brains with more ___ are more plastic, thus likely to show more alterations in neural organization
large; synapses
relatively persistent/permanent change in behaviour that results from experience
learning
when an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased
Hebb synapse
who described the synaptic basis of learning as: learning in which the conjoint activity of nerve cells serves to link them?
Eric Kandel
what happens when the marine slug, Aplysia californica, is threatened?
it withdraws its vulnerable body parts: the gill & siphon
habituation + sensitization are both ___ behaviours for humans
unconscious
learned behaviour in which the response to a stimulus weakens with repeated presentations
habituation
small, fast, random eye movements designed to keep photoreceptors exposed to ever-changing visual stimuli to prevent habitation
saccades
the marine slug, Aplysia californica, ___ to waves in the tidal zone where it lives
habituates
results of habituation
- influx of calcium ions in response to an action potential decreases
- less neurotransmitter released at presynaptic membrane
- less depolarization of postsynaptic membrane
conclusion of Eric Kandel’s experiment on the marine slug Aplysia californica
withdrawal response weakens with repeated presentation of water jet (habituation) due to decreased Ca2+ influx & subsequently less neurotransmitter release from the presynaptic axon terminal
can sensory/motor neurons generate action potentials after habituation?
yes
as habituation develops , the EPSP’s in the motor neuron become ___
smaller
how do the EPSPs in the motor neuron decrease in size as habituation develops?
the motor neuron is receiving less neurotransmitter from the sensory neuron across the synapse, indicating habituation is also taking place in the presynaptic axon terminal of sensory neurons
as habituation happens, the Ca2+ influx ___ in response to the voltage changes associated w/ an action potential
decreases
voltage-activated calcium channels during habituation become ___ responsive to voltage changes + more ___ to the passage of calcium ions
less; resistant
learned behaviour in which the response to a stimulus strengthens with repeated presentations
sensitization
neural results from sensitization
- serotonin reduces K+ efflux thru potassium channels, prolonging an action potential on the siphon sensory neuron
- the prolonged action potential results in more Ca2+ influx & increased transmitter release
- causes greater depolarization of the postsynaptic membrane after sensitization
sensitization vs. habituation
sensitization: influx of Ca2+, more neurotransmitter release, potassium channels
habituation: efflux of Ca2+, less neurotransmitter release, calcium channels
the # and size of synapses ___ in habituation, and ___ in sensitization
decreases; increases
what plays an important role in carrying instructions about structural changes during learning to nuclear DNA?
the second messenger cAMP
in the fruit fly Drosophila, the genetic mutation ___ lacks the enzymes necessary to degrade cAMP, resulting in abnormally high levels, while the other mutation ___ reduces levels of cAMP below the normal range
dunce; rutabaga
fruit flies with both mutations dunce or rutabaga are impaired in acquiring habituation/sensitized responses (learning) bc their levels of ___ cannot be regulated
cAMP
