3. Neuronal transmission Flashcards
Dendrites are the r____ of information from other n____. They have a l____ r____ f____
recipient, neurons
large receptive field
Soma (cell b____) contains the m____ that controls p____ in the cell and i____ information
body, machinery, processing, integrates
Axon carries information (a____ p____) from the s____ to the t____ b____ and once to other cells. Axons can b____ to c____ multiple neurons
action potential
soma
terminal boutons
branch, contact
Terminal boutons/a____ t____ are found at the e____ of the a____ (location of the s____), c____ point with other n____
axon terminals, end, axon, synapse, communication, neurons
Axons can i____ n____ neurons or neurons f____ a____
innervate neighbouring, far away
Neuronal membrane is the b____ of s____, d____, a____ and t____ b____. It separates the e____ environment from the i____ environment
boundary, soma, dendrites, axon, terminal boutons
extracellular, intracellular
(Membrane: Lipid bilayer (5nm))
Protein structures d____ substances o____ of the cell. They allow access of c____ s____ i____ the cell.
They can be gated c____ or e____ and are c____.
detect, outside
certain substances into
chemical or electrical
cytoskeletal
Certain proteins reside in the membrane called r____ that detect c____ m____. The t____ proteins respond to these messages, change c____ and then send signals to i____ the cells called m____ r____
receptors, chemical messangers
transmembrane, confirmation, inside, metabotropic receptors
I____ c____ have a p____ that allows certain i____ to pass through
Ion channels, pore, ions
What are the two types of synapse?
E____ synapses and c____ synapses
Electrical synapses, chemical synapses
Electrical synapses are very r____ in adult mammalian neurons. The j____ between the neurons is very s____. G____ are spanned by p____ which are used to c____ between the neurons (i____ move freely)
rare, junction, small, gap, proteins, communicate, ions
Chemical synapses are c____ in adult mammalian neurons. J____ between neurons is 20-50nm (compared to 3nm in electrical). Chemicals are released from the p____ neuron to communicate with the p____ neurons.
common, junctions, presynaptic, postsynaptic
Chemical transmission was first demonstrated by L____ in the 19__s. Application of f____ following v____ n____ stimulation s____ d____ heart rate. Substance was ‘s____’ to change heart activity.
Loewi, 1920s
fluid, vagus nerve, slowed down, ‘sufficient’
Acceptance as primary means of communication in the brain in ’60s
Overview of chemical transmission:
1. Neurotransmitter s____, t____ and s____
2. D____
3. Open v____-g____ __ channel
4. __ influx
5. Movement and docking of v____
6. E____-d____
7,8. I____ with r____, In/d____ of NTs
- Neurotransmitter (NT) synthesis, transport & storage
- Depolarization (action potential)
- Open voltage-gated Ca2+ channel
- Ca2+ influx
- Movement and docking of vesicles
- Exocytosis-diffusion
7,8. Interact with receptors
In/deactivation of NTs
Neurotransmitters are defined as a c____ that is used to t____ i____ from the p____ neuron to the p____ neuron
chemical, transmit information, presynaptic, postsynaptic
There are four criteria for neurotransmitters:
1. Chemical s____ p____
2. E____ stimulation leads to the r____ of the chemical
3. Chemical produces p____ effect
4. T____ activity
- synthesised presynaptically
- Electrical, release
- physiological
- Terminate
Neurotransmitter binds to receptors on the postsynaptic membrane, which affects the activity of the postsynaptic cell. The configuration of the receptors make them specific for different neurotransmitters.
I____ receptors = opening of an i____ channel
M____ receptors = activates more m____ (s____ m____) in neuron and a____ the s____
Ionotropic, ion
Metabotropic, molecules, second messangers, amplifies, signal
Receptors vary in their p____ - what transmitter b____ to the receptor and how d____ i____
pharmacology, binds, drugs interact
Agonists are drugs (or endogenous ligand/neurotransmitter) that can c____ with a r____ on a cell to produce c____ r____
combine, receptor, cellular reaction
Antagonists are drugs that r____ or c____ b____ the activity of the a____ or endogenous ligand, no c____ e____ after interacting with receptor
reduces, completely blocks, agonist, cellular effect
Receptors vary in their:
1. K____ - r____ of transmitter b____ and channel g____ determine the d____ of effects
2. S____ - what ions are f____
3. C____ - the r____ of f____
- Kinetics, rate, binding, gating, duration
- Selectivity, fluxed (Na+, Cl-, K+ and/or Ca2+)
- Conductance, rate, flux
Ionotropic receptors have fast t____ - ion movement leads to an i____ c____ in the p____ cell
transmission, immediate change, postsynaptic
Excitatory fast transmission:
I____ channel opens
Movement of p____ ions into the neurone
D____
Excitatory p____ s____ p____
Ion channel opens
Movement of positive ions into the neurone (Na+)
(e.g. Glutamate receptors)
Depolarisation
Excitatory post synaptic potential (EPSP)
Inhibitory fast transmission:
I____ channel opens
Movement of n____ ions into the neuron
H____
Inhibitory p____ s____ p____
Ion channel opens
Movement of negative ions into the neurone (Cl-)
(e.g. GABAA receptors)
Hyperpolarisation
Inhibitory post synaptic potential (IPSP)
Activation of a G-protein coupled receptor:
1–N____ b____ to receptor and a____ the G-protein (exchange GDP for GTP)
2–G protein s____ and activates other m____
3–Series of c____ r____ that leads to an a____ of the signal – s____ m____ system
1 - Neurotransmitter, binds, activates
2 - splits, molecules
3 - chemical reactions, application, second messenger
Neurotransmitters must be i____ after use to r____ them from the s____ c___-
inactivated, remove, synaptic cleft
Autoreceptors are located on the p____ t____. They respond to neurotransmitter in the s____ c____. Generally they are G-protein coupled - don’t d____ open i____ channels. They regulate the i____ p____ controlling s____ and r____ of neurotransmitter. N____ f____ mechanism
presynaptic terminal
synaptic cleft
directly, ion
internal process, synthesis, release
negative feedback
Four categories of neurotransmitter:
1. A____ a____ - FAST transmission
2. M____
3. A____
4. N____
- Amino acids - FAST transmission (e.g. GABA, glutamate)
- Monoamines (e.g. dopamine, serotonin)
- Acetylcholine
- Neuropeptides (e.g. endorphin)
Classical neurotransmitters (Amino acids, monoamines, acetylcholine) are synthesised l____ in p____ terminal, stored in s____ v____ and released in response to local increase in__
locally, presynaptic
synaptic vesicles
Ca2+
Neuropeptides are synthesised in the cell s____ and transported to the t____, stored in s____ g____ and have a more i____ stimulation required to release them, hence a more global increase in __
soma, terminal
secretory granules
intense, Ca2+
In excitatory fast synaptic transmission, g____ inotropic receptors in general flux __ which causes an e____ p____ s____ p____ (EPSP) d____ the postsynaptic neuron
glutamate, Na+, excitatory post synaptic potential, depolarising
In inhibitory fast synaptic transmission, G____ inotropic receptors flux __, which causes an i____ p____ s____ p____ (IPSP), h____ the postsynaptic neuron
GABA, Cl-, inhibitory post synaptic potential, hyperpolarising
A____, s____ and A____ activate ionotropic receptors
Acetylcholine, serotonin and ATP
Glutamate is a major f____ e____ neurotransmitter in the CNS and is very w____ through the CNS
fast excitatory, widespread
Activates different types of receptors: mGluR, NMDA, AMPA, Kainate
Glutamate is:
1 synthesised in nerve t____ from g____ or g____
2 loaded and stored in v____ by v____ g____ t____
3 released by e____
4 acts at glutamate r____ on postsynaptic membrane
5 reuptake by e____ a____ a____ t____ in the p____ membrane of presynaptic cell and surrounding g____
1) synthesized in nerve terminals from
glucose or glutamine
2) loaded and stored in vesicles by
vesicular glutamate transporters
3) released by exocytosis (Ca2+ dependent mechanism)
4) acts at Glutamate receptors on postsynaptic membrane
5) Reuptake by excitatory amino acid transporters (EAATs) in the plasma membrane of presynaptic cell and surrounding glia
Based on their pharmacology, three types of ionotropic receptor have been described that respond to glutamate
N____, A____ and K____
NMDA, AMPA and Kainate.
They are named based on the agonists selective for them
AMPA receptor is an i____ receptor. Binding of g____ leads to the opening of a __ channel and hence d____
Ionotropic receptor
Binding of glutamate leads to the opening of a Na+ channel (slight K+ permeability) and hence depolarisation
Selective agonists: A____
antagonists: C___, D___
Selective agonists: AMPA
antagonists: CNQX, DNQX
NMDA receptor is an i____ receptor, permeable to __, __ and __. Upon the binding of glutamate, n____ h____.
Ionotropic receptor
Permeable to Na+, K+ and Ca2+
Binding of glutamate – nothing happens
Voltage dependent blockade in NMDA receptor:
At Resting membrane potential (-65mV):
g____ binds
channel o____
blocked by __
Depolarised membrane (-30mV):
__ pushed out of p____
channel is o____
i____ movement
further d____
*Different ‘ki____’ from AMPA receptor (open
much longer)
At Resting membrane potential (-65mV):
glutamate binds
channel opens
blocked by Mg2+
Depolarised membrane (-30mV):
Mg2+ pushed out of pore
channel is open
ion movement
further depolarisation
*Different ‘kinetics’ from AMPA receptor (open
much longer)
AMPA and kainate receptors: f____ o____ channels permeable to __ and __
Fast opening channels permeable to Na+ and K+
NMDA receptos: s____ o____ channels, permeable to __, __ and __
Also requires g____ as a cofactor and gated by m____ v____.
NMDA receptors are only activated in an a____ d____ m____ in the presence of g____
Slow opening channels – permeable to Ca2+ as well as Na+ and K+
Requires glycine as a cofactor (no glycine, no activation!) And gated by membrane voltage
NMDA receptors are only activated in an already depolarized membrane in the presence of glutamate
Glutamate excitotoxicity is caused by e____ __ i____ into the cell which activates c____ d____ p____ and p____ that damage the cell. This kind of cell damage occurs after s____ and c____ s____
Caused by excessive Ca2+ influx into the cell which activates calcium dependent proteases and phospholipases that damage the cell.
This kind of cell damage occurs after stroke and chronic stress (next lecture)
GABA (g____ a____ a____) is a major i____ neurotransmitter that activates an i____ receptor which opens a c____ channel leading to h____
gamma aminobutyric acid
inhibitory
ionotropic, chloride, hyperpolarisation
1) GABA is synthesized from g____
2) GABA is loaded and stored into
synapses by a v____ GABA
t____
3) GABA released by e____ (Ca2+ dependent mechanism)
4) GABA acts at i____ GABAA and m____ GABAB receptors on postsynaptic membrane
5) GABA cleared from synapse by r____ using t____ on g____ and neurons including non-GABAergic neurons
1) GABA is synthesized from glutamate
2) GABA is loaded and stored into
synapses by a vesicular GABA
transporter
3) GABA released by exocytosis (Ca2+ dependent mechanism)
4) GABA acts at ionotropic GABAA and metabotropic GABAB receptors on postsynaptic membrane
5) GABA cleared from synapse by reuptake using transporters on glia and neurons including non-GABAergic neurons
There are two main families of GABA receptors:
1. GABA_ i____ receptors:
- L____ gated Cl- channel, fast I____
2. GABA_ m____ receptors:
- G protein coupled receptors, i____ coupled to __ or __ channel through s____ m____, slow I____
- GABAA ionotropic receptors
Ligand gated Cl- channel
Fast IPSPs - GABAB metabotropic receptors
G protein coupled receptors
Indirectly coupled to K+ or Ca2+ channel through 2nd messengers (opens K+ channel, closes Ca2+ channel)
Slow IPSPs
Too much GABA leads to s____/c____. AT the right rose, drugs which increase GABA transmission can be used to treat e____
sedation/coma, epilepsy
GHB gamma-hydroxybutyrate is a d____ r____ d____
date rape drug
a GABA metabolite that can be converted back to
GABA by transamination
Increases amount of available GABA
Moderate dose like alcohol, but too much leads to unconsciousness and coma
GABAA is a complex receptor with m____ b____ s____
Two drugs that bind at GABA binding site:
M____ = agonist
B____, p____ = antagonist
Complex receptor with multiple binding sites
Drugs binding at GABA binding site:
Muscimol – agonist
Bicuculine, picrotoxin – antagonist
Drugs increasing GABA activity r____ a____ and drugs decreasing GABA activity i____ a____. These drugs all act at the GABA_ i____ receptor
reduce anxiety
increase anxiety
GABAA ionotropic
Benzodiazepines were discovered in the 19__s. First was c____, shortly after that d____ became the major treatment for anxiety disorders
60s
chlordiazepoxide
diazepam (valium)
Drugs act at the GABAA receptor by changing the k____
kinetics
The two primary neurotransmitters are g____ and G____. They directly m____ the t____ of information between neurons either via a____ or i____ of post-synaptic targets
Glutamate and GABA
mediate, transmission, activation, inactivation
Some neurotransmitters are n____. They affect the response p____ of a neuron.
Some neurotransmitters are ‘Neuromodulators’
Affect the response properties of a neuron (e.g. release, excitability)
-do not carry primary information themselves.
e.g. dopamine, serotonin
(others: histamine, neuropeptides)
The Diffuse Modulatory Systems are specific p____ of neurons that project d____ and m____ the activity of glutamate and GABA neurons in their t____ areas
populations
diffusely, modulate, target
Cell bodies of dopamine neurons are in the m____ and project into the f____
midbrain, forebrain
Within the dopaminergic system, the n____ system has a role in m____
Nigrostriatal system (substantia nigra projections to neostriatum (caudate and putamen))
role in movement.
dysfunction:
Parkinson’s disease - destruction of DA projections from SN to basal ganglia
Huntington’s disease - destruction of DA target neurons in striatum
Within the dopaminergic system, the m____ Systemj has a role in r____
Mesolimbic system (ventral tegmental area projections to nucleus accumbens (NAcc))
role in reinforcement (reward)
dysfunction:
Addiction - most drugs of abuse lead to enhanced DA release in the NAcc
Within the dopaminergic system, the m____ system has a role in functions such as w____ m____ and p____
Mesocortical system (VTA projections to prefrontal cortex)
role in functions such as working memory and planning.
dysfunction: Schizophrenia
Dopamine synthesis:
T____ -> (catalysed by tyrosine hydroxylase (TH), called the r____ l____ step) L____ -> (catalysed by dopa decarboxylase) D____
Catecholamine storage - loaded into v____
Dopamine synthesis:
Tyrosine (essential amino acid obtained in diet)
catalyzed by tyrosine hydroxylase (TH)
RATE LIMITING STEP (or slowest step)
–> L-Dopa
catalyzed by dopa decarboxylase
–> Dopamine
Catecholamine storage
Loaded into vesicles
Drugs that affect dopamine synthesis and storage modulate behaviour:
1. R____ impairs storage of m____ in s____ v____
2. L____, the precursor of dopamine, is used as a treatment for P____ disease
- Reserpine impairs storage of monoamines
in synaptic vesicles. (The vesicles remain empty
resulting in no transmitter release upon activation) - L-DOPA, the precursor of dopamine, is used as a treatment for Parkinson’s disease. (Bypasses rate-limiting TH step – Dopa decarboxylase converts it into dopamine increases the pool of releasable transmitter)
Dopamine release:
1. D____ of presynaptic membrane
2. Influx of __ through v____ g____ __ channels
3. __ dependent v____ d____ and release
- depolarization of presynaptic membrane
- influx of Ca2+ through voltage gated Ca2+
channels - Ca2+ dependent vesicle docking and Release
(Ca2+ dependent exocytosis)
Dopamine reuptake/metabolism:
- Signal terminated by r____ into the axon terminal by t____ powered by e____ g____
- In cytoplasm dopamine is:
. r____ back into vesicles
. e____ d____ by m____ o____
- Signal terminated by reuptake into the axon terminal by transporters powered by electrochemical gradient (Dopamine transporters (DATs))
- in the cytoplasm dopamine is:
. reloaded back into vesicles
. enzymatically degraded by Monoamine oxidases (MAOs)
The Serotonergic system is nine r____ n____ (in brain stem) with d____ projections, each projects to a different part of the brain. D____ projections to c____ and s____ c____. Dorsal and medial r____ project throughout c____ c____
raphe nuclei
diffuse
Descending, cerebellum, spinal cord
raphe, cerebral cortex
Serotonin synthesis:
T____ -> (r____ l____ step) 5-h____ -> s____
Tryptophan (essential amino acid obtained in
diet)
RATE LIMITING
–> 5-hydroxytryptophan (5-HTP)
–>Serotonin (5-hydroxytryptamine, 5-HT)
Serotonin storage = loaded into v____
Serotonin release = __ dependent e____
Serotonin reuptake/metabolism = signal terminated by r____ by Serotonin t____ on presynaptic membrane, degraded by M____ in the c____
vesicles
Ca2+, exocytosis
reuptake, transporters, MAOs, cytoplasm
