ICL 3.1: Synaptic Transmission Flashcards
how do neurons communicate with each other and other peripheral structures?
through the generation of chemical and electricalsignals
what is a synapse?
the junction point from one neuron to the next
what are the two types of synapses?
- chemical
- electrical
these can be either excitatory or inhibitory
how do electrical synapses work?
gap junction proteins (connexons) aggregate to form an aqueous channel
action potentials are then transmitted through gap junctions –> no synaptic vesicles of significant synaptic cleft
the molecules passing through could be ions like Ca+2 or other small molecules like ATP
signal transmission is bidirectional
electrical synapses are the fasts way neurons communicate with one another!
how do chemical synapses work?
this type of synapse is the most abundant in the human CNS
the way it works is that the presynaptic neuron secretes a neurotransmitter which then binds to receptor proteins in the membrane of the postsynaptic neuron
the NTs will either modulate, stimulate or inhibit the postsynaptic neuron
signal transmission is unidirectional
what are the basic components of a chemical synapse?
- synaptic cleft
- transmitter vesicles
- post synaptic neuronal membrane
- mitochondria
what is the synaptic cleft?
it separates the presynaptic terminal from the postsynaptic neuron
what is the function of the presynaptic terminal?
the terminal hastransmitter vesicles and themitochondria
transmitter vesicles contain neurotransmitters
what is the function of the postsynaptic neuronal membrane?
it containsexcitatory or inhibitory receptors
what is the function of mitochondria in a chemical synapse?
mitochondria provide ATP to use as an energy source for neurotransmitter synthesis
what are the events that happen at a chemical synapse?
- an action potential depolarizes the presynaptic membrane
- voltage gated Ca2+ channels on the presynaptic membraneopen and a large number of Ca2+ ions enter the presynaptic terminal
- Ca2+ entry leads to the exocytosis of synaptic vesicle contents
- NTs are released into the synaptic cleft
- NTs bind to receptors on post synaptic membrane
- brief opening of specific ion channels
- NTs are soon released and degraded or recycled
how much neurotransmitters are released at a chemical synapse?
Quantity of neurotransmitter released is directly related to the number of Ca2+ ions that enter the presynaptic neuron
after an event at a chemical synapse, how is the synaptic cleft cleared?
- Its can be returned to axon tmerinals for reuse or transported into glial cells
- enzymes can inactivate NTs
- NTs can diffuse out of the synaptic clef
what breaks down acetylcholine?
acetylcholinesterase
ACh is made from choline and acetyl CoA –> in the synaptic cleft, ACh is broken down by acetylcholinesterase and the choline is transported back into the axon terminal and used to make more ACh
how do synaptic vesicles in the presynaptic neuron exocytose their NTs into the synaptic cleft?
the synaptic vesicles dock at defined sites on the target plasma membrane –> the SNARE family of proteins is what mediates the docking of the transport vesicles with the target membrane
Ca2+ influx triggers the fusion leading to the opening of the pore
once the vesicles fuse with the membrane, NTs are related into the synaptic clef
what is the MOA of botulism?
Botulinum neurotoxins are synthesized primarily by different strains of the anaerobic bacteriaClostridium botulinum
botulinum toxin, or botox, is used in the therapeutic setting to reduce muscle tension, toreduce muscle spasticity
the botox injection work by weakening or paralyzing certain muscles or by blocking certain nerves
they do this by cleaving SNARE complex proteins which prevents the fusion of vesicles to the plasma membranes
what are the 2 major classes of neurotransmitters?
- small molecule transmitters
ionotropic receptors and metabotropic receptors
- peptide transmitters
metabotropic receptors
what are small molecule transmitters?
they’re the most acute and rapid responses
they’re used for the transmission of sensory signals to the brain and of motor signals back to the muscles
class I-IV: examples include ACh, epinephrine, serotonin, histamine, glycine, nitric oxide etc.
where are small molecule transmitters synthesized?
they’re synthesized in the cytosol of the presynaptic terminal and absorbed by active transport into transmitter vesicles
what are the 8 important small molecule neurotransmitters?
- acetylcholine
- norepinephrine
- dopamine
- serotonin
- glutamate
- nitric oxide
- glycine
- GABA
what is the function of acetylcholine?
a small molecule neurotransmitter
it’s a majorexcitatory neurotransmitter of somatic motor neurons
it has some inhibitor effects like the inhibition of the heart by the vagus nerves
it also has a modulatory role in cognitive functions like paying attention
what is the function of norepinephrine?
a small molecule neurotransmitter
it’s mostly excitatory and is secreted in the brain stem and hypothalamus
it controls overall activity and mood of the mind – so your sense of feeling good or being alert
it also increases heart rate and BP
what is the function of dopamine?
a small molecule neurotransmitter
it’s released from the brain and it mediates various aspects of cognition
so it facilitates your sense of feeling good and your reward pathway
in Parkinson’s, there’s a loss of dopamine neurons in the midbrain-substantial nigra
what is Parkinson’s MOA?
in Parkinson’s, there’s a loss of dopamine neurons in the midbrain-substantial nigra
as the substantia nigra degenerates in Parkinson’s disease, the nigrostriatal pathway is disrupted, reducing striatal dopamine and producing PD symptoms
what is the function of serotonin?
a small molecule neurotransmitter
that’s released from the brain and it mediates various aspects of cognition
it’s an inhibitor of pain pathways in the spinal card
it also regulates endocrine activity aka hormonal controls!
its also involved in the mood of a person and controls sleep/wake cycles; it causes sleepiness
what happens if someone has inadequate serotonin levels?
- severe depression
- obsessive/compulsive disorders
- anger issues
- eating disorders
what is the function of glutamate?
a small molecule neurotransmitter that is secretes and concentrated in the brain
it’s the major excitatory neurotransmitter in the CNS
what is the function of nitric oxide?
a small molecule neurotransmitter that’s secreted by nerve terminals in areas of the brain responsible for long-term behavior and memory
it’s synthesized instantly as needed and diffuses out of the presynaptic terminals and then into postsynaptic neurons
it changes intracellular metabolic functions that modify neuronal excitability in the postsynaptic neuron
what is the function of glycine?
a small molecule neurotransmitter that is secreted mainly in the spinal cord
it is inhibitory*
it’s also a co-transmitter for some glutamate receptor (binding is important for the activity)
what is GABA?
a small molecule neurotransmitter secreted in the spinal cord and CNS
it’s the most important inhibitory transmitter int he brain!!!
it’s what inhibits NTs that cause anxiety
what are benzodiazepines? give examples
benzodiazepines are tranquilizers that are used for anxiety and insomnia
they work with GABA to limit anxiety
ex. valium (diazepam) and xanax (alprazolam)
what are peptide transmitters?
neuropeptides have slower but longer lasting effects (days, months or years)
they’re present in smaller quantities but are more potent
where are peptide transmitters synthesized?
they’re synthesized by ribosomes in the neuronal cell body
they undergo packaging in the ER and subsequently the golgi
then, vesicles are transported to the tips of the nerve fibers byaxonal streaming (slow process)
what are the two types of receptor proteins of a synapse?
the membrane of the postsynaptic neuron contains a large numbers ofreceptor proteins
- ionotropic receptors
- metabotropic receptors
each receptor has an extracellular components that protrudes into the synaptic cleft and binds the neurotransmitter
there’s also an intracellular component extending into the interior of the postsynaptic neuron
what are ionotropic receptors?
a type of receptor in a synapse that gates ion channels directlyand allows for passage of specific ions
so they’re membrane-bound receptor proteins that respond to ligand binding by opening an ion channel and allowing ions to flow into the cell, either increasing or decreasing the likelihood that an action potential will fire
there are both cation channels and anion channels
they’re fast and precise
what are metabotropic receptors?
a type of receptor in a synapse that activates “second messengers”
so there are molecules that activate other substances inside the cytoplasm of the postsynaptic neuron
prolonged postsynaptic neuronal excitation or inhibition (such as memory) is achieved by activating a “second messenger” chemical system inside the postsynaptic neuronal cell
ex. G proteins
what are cation channels?
usually for Na+ ions but can also be for K+ or Ca+2
the channels are lined with negative charges to attract positively charged Na+ ions –> negative chargesrepel Cl- ions and other anions& prevent their passage
ions will enter when the channel diameter > size of the hydrated Na+ ion
what are anion channels?
they mainly allow Cl- ions to pass but also minute quantities of other anions
Na+, K+ and Ca2+ ions are blocked because of the size of their hydrated ions
how do G proteins work?
they’re a type of metabotropic receptor system
the inactive G protein complex is free in the cytosol but it undergoes a conformation change when a receptor is activated by a neurotransmitter
this leads to a series of cellular events via secondary messengers including the opening of ion channels
what different things can secondary messengers in a metabotropic receptor system do?
- opening specific ion channels – often stays open for a prolonged time unlike ion channels
- activation fo cAMP or cGMP which then in turn activate highly specific neuronal metabolic machinery and initiate any one of many chemical results
- activation of one or more intracellular enzymes – the enzymes in turn can cause any one of many specific chemical functions
- activation of gene transcription – this can lead to formation of new proteins which in turn changes nruronal metabolic machinery or structure
what’s the resting membrane potential of a spinal motor neuron?
the soma of a spinal motor neuron has aresting membrane potentialof ~ − 65 mV
synaptic potentials arise when neurotransmitters activate ion channels
what 2 synaptic potentials are there?
- excitatorypostsynaptic potential (EPSP)
opening of Na+ or Ca2+ channels leads to depolarization of the membrane
- inhibitorypostsynaptic potential (IPSP)
opening of K+ or Cl- channels leads to hyperpolarization of the membrane
what are excitatorypostsynaptic potentials?
they arise at synapses where the transmitter depolarizes the synaptic membrane
opening of Na+ or Ca2+ channels leads to depolarization of the membrane
however, a single EPSP cannot induce an action potential – EPSPs added together can reach the threshold and trigger a postsynaptic cell
what are inhibitory postynspatic potentials?
they at synapses where the transmitter hyperpolarizes the synaptic membrane
opening of K+ or Cl- channels leads to hyperpolarization of the membrane
so the excitatory neurons have to have a higher potential than the inhibitory neuron for an action potential to happen
what is summation in neurons?
one synapse is not strongenough to reach the threshold potential in the post synapticneuron
instead, multiple inputs summate their post-synaptic potentials inthe same region of the dendrite at the same time to generate an action potential
generation of an action potential depends on the summation of EPSPs and IPSPs
so ultimate, the algebraic sum of all the EPSPs and IPSPs has to raise the membrane potential to the threshold potential for an action potential to occur
however, if the IPSPs prevail, then the post-synaptic cell will be “silent”
what is spatial summation?
many presynaptic terminals when stimulated at the *same time *can add up to exceed the threshold potential
so it is the effect of triggering an action potential in a neuron from one or more presynaptic neurons
what is temporal summation?
rapidsuccessive discharges from a single presynaptic terminal can add up to exceed the threshold potential
what are modulatory transmitters?
modulatory transmitters alter the response of fast ionotropic transmitter actions
they mediate by altering the opening states of K+ or Ca2+ channels by altering membrane potential and the refractive period
so they can keep the membrane depolarized or hyperpolarized even after the initial impulse ends
ex. excitatory synaptic inputs from cerebral cortex to motor neuron are modulated by slow modulatory synaptic inputs from brain stem (degree of motivation) determining the speed of the movement
what is the function of inhibitory synapses?
they maintain homeostasis!!
they dampen the excitation that could lead to neuronal damages
they’re important for streamlining relevant and precise sensory information
they’re also important for locomotion
note: drugs against epilepsy usually targets inhibitory transmitters and increase their effect
what is disinhibition?
when 2 inhibitory neurons coupled in series increase the activity of an excitatory neuron
what is strychnine?
it blocks inhibitory glycinergic synapses and causes life threatening muscle spasms
what is synaptic plasticity?
life experiences change the nervous system!
the brain can change and adapt to new information and also there is the basis of memory, acquisition of motor and cognitive skills
plasticity is broadly categorized into short and long term plasticity
what is the mechanism of synaptic plasticity?
- presynaptic terminal releases more/less neurotransmitter in response to an action potential
OR
- postsynaptic neuron increases/decreases its response to the transmitter
what is short term plasticity?
changes in synaptic strength that occur on a sub-second time scale and reverts to “normal” soon afterwards
- facilitation
- potentiation
- short term depression
what is facilitation?
increased transmitter release by presynaptic neuron
what is potentiation?
increased synaptic efficiency even after the stimulation ends
what is short term depression?
weaker post-synaptic response
what is long term plasticity?
it can last anywhere from minutes to hours, days, or years
this is the dominant model for how the brain stores information!
- long term potentiation
- long term depression
what is long term potentiation?
persistent strengthening of a synaptic connection
what is long term depression?
long-term weakening of a synaptic connection
what are the steps in long-term potentiation?
- glutamate is released from the presynaptic neuron and acts on two receptors: AMPA and NMDA
- Na+flows into the postsynaptic neuron only through the AMPA receptor (since Mg2+blocks NMDA receptor )
- depolarization of the postsynaptic cell removes Mg2+block on NDMA receptor
- Na+and Ca2+ flow through NMDA receptor into postsynaptic neuron
- [Ca2+] initiates activation of protein kinase-mediated signaling cascades
- this increases the number and sensitivity of AMPA receptors
what is late phase long-term potentiation?
when sustained activation of the early phase kinases initiates signal cascades leading to protein synthesis, morphological changes of the neuron, and gene expression
this includes both postsynaptic changes and presynaptic changes
- postsynaptic changes = increased dendritic area and spines which increase postsynaptic sensitivity or increase in AMPA receptors inserted in the postsynaptic membrane
- presynaptic changes = increased binding and release of neurotransmitter vesicles from the presynaptic membrane or increase in the total number of presynaptic neurotransmitter vesicles
these are the underlying mechanisms for learning and addiction!
what is long term depression?
long term depression decreases the efficacy of a synapse
observed in cerebellum (motor learning), hippocampus (memory decay),the visual cortex, and the prefrontal cortex
mechanism proceeds due to low frequency stimuli and a slow rise in postsynaptic [Ca2+]
example:activation of phosphatase-mediated signaling resulting in the internalization of AMPA receptors
what is the MOA of lead poisoning?
Blocks NMDA receptors limiting synaptic plasticity and memory
lead accumulates around nerves causing them to degenerate and demyelinate. It also inhibits heme synthesis pathway leading to the build up of substrate δ-Aminolevulinic acid (ALA)which is directly toxic to neurons. Thirdly it blocka NMDA receptors. Effects are particularly potent among children since it interferes with normal neurologic development.
this causes acute encephalopathy through multiple mechanisms
what is the correct order in a normal flexion reflex?
- AP in sensory afferent neuron
- EPSP in interneuron
- AP in interneuron
- EPSP in motor neuron
- AP in motor neuron
- AP in flexor muscle
- contraction of flexor muscle
at the negative resting membrane potential, the NMDA receptors little ionic current because…..
they are blocked with Mg+2
what creates the barrier that is the reason for chemical synapse discontinuity?
the synaptic cleft
what is the most direct cause for the presynaptic vesicles to fuse with the presynaptic membrane and release a neurotransmitter into the synaptic cleft?
release of calcium ions into the presynaptic neuron terminal
______ receptor has a direct, mechanical response to the binding of a neurotransmitter?
ionotropic
_____ is the major inhibitory neurotransmitter in the CNS
GABA
when would you expect to see an increase in Cl- ions in the neurons? during EPSP or IPSP?
IPSP
when Cl- enters the neuron, it hyperpolarizes the neuron and it’s inhibitory
long term depression involves…..
protein phosphatase mediated internalization of the AMPA receptors
