Chapter 3: Chemical Signaling by Neurotransmitters and Hormones Flashcards
What is the direction of signal transmission in neuron communication?
from presynaptic cell to postsynaptic cell
Synaptic cleft:
gap between the terminal and dendrites of neighboring cells
Postsynaptic density:
dendrites facing the synaptic cleft are filled with neurotransmitter receptors
** this makes them appear darker and somewhat fuzzy
List the three types of synaptic clapses:
- axodendritic
- axosomatic
- axoaxonic
What is the most common synapse of the brain?
axodendritic
Presynaptic inhibition vs presynaptic facilitation:
reduction and enhanced release of transmitter release
Neuromuscular junction:
the connection point between a neuron and a muscle
Neurotransmitters:
chemical substances released by neurons to communicate with other cells
The major categories of neurotransmitters can be separated into which two groups?
- classical
2. nonclassical
What are the classical neurotranmitters?
Try to list examples of each!
- amino acids (GABA/glutamate)
- monoamines (Dopamine (DA)/Norepinephrine (NE)/ Serotonin (5-HT)/ Histamine (HA))
- acetylcholines (Adenosine triphosphate (ATP))
List the nonclassical neurotransmitters:
- neuropeptides
- lipids
- gases
What are some neuropeptides?
- endorphins and enkephalins
- corticotropin-releasing factor (CRF)
- Orexin/hypocretin
- Brain delivered neurotrophic factor (BDNF)
What are some examples nonclassical gas neurotransmitters?
- nitric oxide (NO
- carbon monoxide (CO)
- hydrogen sulfide (H2S)
T/F: A neuron can release more than one type of transmitter.
true
T/F: All NT are synthesized in the same manner.
false not neuropeptides
Typically NT are synthesized by […] that can occur […] in the cell.
enzymatic reactions; anywhere
Neuropeptides have a precursor of […] which can only be made in the […].
proteins; cell body (soma)
What else needs to be present in order to fully produce neuropeptides?
large vesicles to transport
What is the important site for NT synthesis?
axon terminals
Neuromodulators:
chemicals that don’t act like typical neurotransmitters
NM could […], enhance, or […] NT effectivness.
prolong; reduce
Volume transmission:
diffusion away from the site of release to influence cells more distant from the releasing cell than at the standard synapse
Criteria to determine if an endogenous substance is an NT (6)?
- SYNTHESIZED: presynaptic cell contains the chemical substance and a mechanism to synthesize it
- INACTIVATION: a mechanism for inactivating the actions of the chemical should be present
- RELEASED: the chemical released from axon terminals during neural stimulation
- RECEPTORS: receptors for the substance are present on the postsynaptic cell
- IDENTICAL PATHWAY: direct application of the chemical (or the agonist) has the same effect on the post-synaptic cell as if stimulating the presynaptic neuron
- AFFECTED BY ANTAGONIST: application of an antagonist that blocks the receptors inhibits both the chemical’s action and the effects of stimulating the presynaptic neuron
What are some of the characteristics of gaseous and lipid transmitters (5)?
- readily pass through membranes by simple diffusion
- cannot be stored in synaptic vesicles
- must be made “on demand”
- typically released by postsynaptic cells
- actions on presynaptic cells or adjacent axons or glial cells
Retrograde NT gas examples:
nitric oxide
Nitric oxide has a role as a […] it interacts with […] in both the […] and […] sites.
neuromodulator; 2nd messengers; presynaptic; postsynaptic
Retrograde NT lipid examples (2):
anandamide and 2-arachidonoylglycerol
Reticulum Theory:
Camillo Golgi proposed that the nervous system consisted of a series of vastly interconnected continuous networks
Neuron Doctrine:
Santiago Ramon y Cajal proposed the nervous system is composed by individual cells that are not physically connected
Reticulum theory is that information flow is in […]. Neuron doctrine is that information flow is mostly […].
any directions among elements; unidirectional from one cell to the other
Neurophysiologists argued that communication between neurons occurred by means of […] crossing the gap between axons and dendrites.
electrical currents
Pharmacologists in contrast argued that information between neurons is transmitted by releases of […]
neurotranmitters
Anterograde Transmission:
the main direction of most transmission in the brain from presynaptic to postsynaptic
Axodendritic synapses:
presynaptic axon terminals release NT to postsynaptic dendrites
Axosomatic synapses:
axon terminals makes synapses on the cell body (somata) of postsynaptic cells
Axoaxonic synapses:
axon terminals make synapses on axon terminals of other neurons
Presynaptic inhibition:
a mechanism that reduces transmitter release from the terminal
What is the prime example of presynaptic inhibition?
axoaxonic synapses
Presynaptic facilitation:
enhanced release of transmitter release
What are the two types of NT?
- classical
2. nonclassical
List the 3 main classical NT:
- AA
- monoamines
- ACh
List the 3 main nonclassical NT:
- neuropeptides
- lipids
- gaseous transmitters
T/F: A neuron can release more than one type of transmitter.
true
What is the one NT that is synthesized by a unique mechanism?
neuropeptides
Typically, NT are synthesized by […] that can occur […] in the cell.
enzymatic reactions; anywhere
Required parts for NT synthesis are shipped in large quantities to the…
axon terminals
What is the important site for NT synthesis?
axon terminals
Neuropeptides have a precursor of […] which can only be made in the […].
proteins; cell body
What else has to be present for neuropeptide synthesis (besides proteins)?
large vesicles in order for proteins to be transported down to the axon terminals
Neuromodulators (NM):
chemicals that don’t act like typical NT
NM could […], enhance, […] a NT […].
prolong; reduce; effectiveness
NM could interact through […].
volume transmission
Volume transmission:
diffusion away from the site of release to influence cells more distant from the releasing cell than is the case at a standard synapse
Classical transmitter release involves […] and […] of synaptic […].
exocytosis; recycling; vesicles
Step of NT release from the terminal (5):
- action potential
- depolarization wave
- Ca2+ ion voltage channels open
- rapid influx of Ca2+ ion in the terminal
- NT release
Active sites:
specialized regions near the postsynaptic cell that are release site for NT
Synaptobrevin: […] that plays a key role in helping the vesicle […] with the […] during […].
protein; fuse; axon terminal membrane; exocytosis
If the synaptobrevin mechanism were to be negatively affected by toxins, what could occur?
paralysis: no muscle contraction due to no exocytosis
Vesicle recycling: What is it and what does it cause?
synaptic vesicle fusion causes it’s membrane to be temporarily part of the terminal membrane
What are the 2 benefits of vesicle recycling?
- prevents depletion of synaptic vesicles (neuron is firing rapidly and many vesicles are releasing their contents into the synaptic cleft
- prevents accumulation of vesicle membrane within the membrane of the nerve terminal
Clathrin: a […] that forms a coating on the […] that is needed for […] and vesicle […].
protein; membrane; invagination; retrieval
Ultrafast endocytosis:
vesicle retrieval occurs extremely quickly in an area close to the release site
Ultrafast endocytosis is completed with the help of…
endosomes
Endosomes:
intracellular organelles that join in vesicle retrieval during ultrafast endocytosis
Kiss-and-run:
vesicle fuses with the nerve terminal membrane merely to allow the NT molecules to escape the vesicle interor
Bulk endocytosis:
used to retrieve large amounts of vesicle membrane that have fused with the nerve terminal membrane
What are some types of endocytosis?
- clathrin-mediated endocytosis
- ultrafast endocytosis
- kiss-and-run
GABAergic cells typically release…
- parvalbumin (PV)
- somatosin (SOM, SST)
- cholecystokinin (CCK)
- vasoactive intestinal peptide (VIP)
How can you reduce presynaptic activity?
reduce AP
Autoreceptors:
receptor for the same kind of transmitter that has been released
Autoreceptors provide a […] to inhibit/control NT release.
NFB
What are the two types of autoreceptors?
- terminal AR
2. somatodendritic AR
Terminal AR is located at […] terminals to […] NT release.
presynaptic; inhibit
Somatodendritic AR is located at […], when activated by […] NT release, it […] the rate of NT release.
cell bodies/dendrites; local; slows down
Heteroreceptors provide…
presynaptic release-modulating effects
What are 2 mechanisms for NT inactivation?
- heteroreceptors
2. autoreceptors
At axonal synapses, these receptors can inhibit the release of other NTs.
heteroreceptors
T/F: Heteroreceptors only inhibit NT release.
false; they hold modulating effects, thus, they can enhance as well
Mechanisms for NT removal from the synaptic cleft:
- enzymatic breakdown
- reuptake transporters
- uptake transporters
NT removal: What is the most common mechanism for neuropeptides, lipids, and NO?
enzymatic breakdown
NT removal: Reuptake transporters move NT molecules […]. An example of this is the […] transporter.
back to the axon terminal; serotonin
NT removal: Uptake transporters move NT molecules […] into nearby […] cells.
away from the synaptic cleft; glial
NT removal: What is the most common mechanism for glutamate and GABA?
Uptake transporters
Receptors:
membrane proteins that bind NT
Presynaptic Receptors are…
autoreceptors or heteroreceptors
Postsynaptic receptors main role:
pass signal to the postsynaptic cell
Postsynaptic receptors are activated by […].
NT
After activation of postsynaptic receptors, what can result in regards to the environment?
- inhibition or excitation
2. neuromodulation
After activation of postsynaptic receptors, what can result in regards to the NT?
- disengage and activation of other receptors until inactivated
- degraded or reabsorbed
Receptor subtypes example…
GABA binds on GABAa and GABAb
Receptor subtypes can be located in different…
- compartments of neurons (somata vs. dendrites)
- side of the synapse (pre vs. post-synaptic)
- neuron types
- brain regions
Drugs that are designed to affect specific subtypes result in…
fewer side effects
Ionotropic receptors have a […] but […] response.
fast; short
Ionotropic consists of […] subunit(s) with an […].
4-5; ion channel in the center
If an NT binds to an ionotropic receptor, what occurs?
channel opening for flow of ions
Ionotropic receptors are referred to as […].
ligand-gated channel receptors
Na+ = […] K+ = […] Cl- = […] Ca2+ = […]
depolarizes; hyperpolarizes; hyperpolarizes; depolarizes
Metabotropic receptors have a […] but […] response.
slow; prolonged
Metabotropic receptors consist of […] subunit(s) that has […].
one; 7 transmembrane domains
Metabotropic is coupled with…
2nd messengers
Metabotropic receptors respond to NT binging by work via […], and are typically referred to as […] receptors.
G-proteins; G-protein-coupled
G-protein stands for…
guanine nucleotide-binding proteins
Gs = […] Gi = […] Gq = […]
stimulation; inhibition; activation
In neurons, G-proteins can act via…
- ion channels
2. effector enzymes
Metabotropic receptors: Where are effector enzymes located?
on the membrane just like ion channels
Gs example = […]
Gi example = […]
Gq example = […]
increase cAMP; decrease cAMP; via PLC and IP3
Effector enzymes and second messengers.
EE can synthesize or break them down
Allosteric sites on receptors:
additional binding sites on ionotropic or metabotropic receptors
Allosteric receptors function ONLY when there’s a presence of…
agonist (or NTs) in the main binding site
[…] are allosteric modulators and are engineered to bind to alter […].
drugs; receptor function
If an allosteric modulator is given alone, what is the resulting signal?
nothing; there needs to be a presence of an agonist
Agonist alone = […]
Agonist + PAM = […]
Agonist + NAM = […]
PAM or NAM alone = […]
normal signal; increase in signal; decrease in signal; no signaling
First messengers:
NTs
Second messengers:
intracellular molecules or ions that keep carrying out signals from the first messengers
Second messengers activate […], which in turn activate other proteins via […].
protein kinases; phosphorylation
Kinases can trigger many other […] to activate various […].
proteins; molecular cascades
Activation of nuclear proteins leads to…
changes in gene expression
Common 2nd messengers (4):
- cAMP
- cGMP
- Ca2+
- IP3/DAG
cAMP = stimulates […] cGMP = stimulates […] Ca2+ = stimulate […] IP3/DAG = result from […]
protein kinase A (PKA); protein kinase G (PKG); protein kinase C (PKC); breakdown of phosphoinositide
Calcium/calmodulin kinase (CaMK):
mediates Ca2+ activation of protein kinases (phosphoinositide)
What is synaptic plasticity?
changes in structural/functional features of synapses (leads to synaptic strength)
What causes synaptic changes?
sensory experience, learning, memory formation, and psychoactive drug use
What kind of changes occur to synaptic plasticity?
- formation of new synapses
- adjustments in existing synapses (protein pools, molecular machinery, receptor densities)
- growth of spines, dendrites, axon terminals
What are examples of molecular cascades (5)?
- mitogen-activated protein kinase system (MAPK)
- Ca2+ dependent molecules (calcium calmodulin)
- cAMP, PKA, PKC, etc.
- actin and myosin
- gene expression and synthesis of new proteins
Spines are somewhat pruned during […] but retain […] ([…]).
adolescence; plasticity; memory
Spines play an important role in […].
long-term memory
Neurological disorders are associated with […].
abnormal levels of spines
Key players in synaptic plasticity:
- molecular cascades
2. spines
