2 - Introduction to neurotransmission lecutre Flashcards
describe the cell body of a neuron
nucleus, stores DNA and rough ER, which builds protein and mitochondria
describe dendrites
- the input region
- have lots of receptors
- receive input from other neurons
describe the axon
- main conduction unit
- carries info in the form of electrical signal known as the action potential (AP can vary in length)
- surrounded by myelin sheath — speeds up conduction, insulator
describe axon terminals
- the output region
- release of neurotransmitter
- aka. synaptic terminals
- electrical —> chemical signal
how do neurons communicate with each other?
synapses
at the chemical synapse the pre and postsynaptic elements are separated by a gap called the ________?
synaptic cleft
what are subcortical nuclei in the basal ganglia?
collections of cell bodies/neurons that project from one region to another
what does the AP do at the presynaptic terminal?
the AP opens Ca++ channels and initiates neurotransmitter release
what results in release of neurotransmitter?
Ca++ influx
describe the events from an AP arriving at a presynaptic terminal to the recycling of the neurotransmitter
- when an AP arrives at the presynaptic terminal it causes the opening of voltage gated Ca++ channels and Ca enters the cell
- Ca causes the vesicles to bind to the presynaptic membrane
- neurotransmitter is released into the synapse by exocytosis
- the neurotransmitter binds to receptors on the postsynaptic membrane, and the receptor determines if an excitatory or inhibitory signal is passed on
- the neurotransmitter is then broken down or directly taken back up into the presynaptic terminal by transporters where it is recycled
describe exocytosis at the synaptic cleft
- presynaptic vesicles bind to the presynaptic membrane
- transmitter is then pushed out into the synaptic cleft
- in response to the arrival of the AP
what is an agonist?
a substance which stimulates the receptors and mimics the natural ligand (eg. neurotransmitter, hormone)
what is an antagonist?
substances that block the receptor and prevents/stops the effect of the natural ligands — no activation of receptor
what is a partial agonist?
- an agonist which is unable to induce maximal activation of a receptor population, regardless of the amount of drug applied
- not as much activation of receptor as full agonist
describe inotropic receptors
- receptor is part of a ligand-gated ion channel protein and activation results in ion conductance charges
- these receptors are opening by the transmitter to allow the passage of Na+ (excitatory) or K+/Cl- ions (inhibitory) and are involved in fast transmission
- involves conformational shift
- examples : Ach, Glu, GABA
how does a conformational shift cause release of an excitatory signal?
conformational shift — Na+ rushes in — depolarisation — excitatory signal
what is GABA and how does it cause an inhibitory signal?
= a major inhibitory neurotransmitter in the CNS
- ion channels might be specific for something like Cl-
- Cl- rushes in
- pushes cell further away from membrane threshold for the AP
- inhibitory signal
describe metabotropic receptors
- slower
- receptor protein in membrane is coupled to effector mechanism via G-proteins
- in this signalling mechanism, agonist molecule combines with receptor proteins in the membrane
- the resulting conformational change causes activation of a membrane-associated enzymes via G-protein
- the cellular effect is usually much slower than that associated with ionotropic receptors
describe dopamine synthesis
L-tyrosine —> L-dopa —> dopamine
- tyrosine hydroxylated for first arrow
- dopa decarboxylase (DDC) for second arrow
what is the rate-determining step in dopamine synthesis and why?
tyrosine hydroxylase (L-tyrosine —> L-Dopa) as it is normally saturated by substrate
describe dopa decarboxylase
- high activity
- non-specific
where is dopamine stored?
in synaptic vesicles in the axonal terminal
how is dopamine released?
- released into the synaptic cleft upon the arrival of an AP and influx of Ca++ by exocytosis
- released and binds to postsynaptic receptors:
D1 family (D1 + D5) = excitatory
D2 family (D2/3/4) = inhibitory
what are 2 methods of dopamine inactivation/reuptake?
1) metabolism by enzymes — break down dopamine
- catechol-O-methyltransferase (COMT)
- monoamine oxidase (MAO)
> both present in terminals + synapse
2) reuptake processes
- catecholamines have highly specific active transport mechanisms to remove transmitter from synapse into presynaptic terminal
directly take dopamine back out of terminal + recycle + repackage it into vesicles
DAT = dopamine transporter
what are the 4 dopamine pathways?
- nigrostriatal pathway
- mesolimbic pathway
- mesocortical pathway
- tuberoinfundibular pathway
summarise the dopamine pathways
why is l-tyrosine not given to people in Parkinson’s?
more L-dopa would not be made as the tyrosine hydroxylase (RDS) is saturated
what is glutamate?
the major excitatory neurotransmitter in the CNS
what neurotransmitter is released at the neuromuscular junction?
acetylcholine
what neurotransmitter is diminished in the substantia nigra in Parkinson’s disease?
dopamine
summarise the parasympathetic pathway
where do pain pathways cross the midline?
spinal cord
where do proprioceptive pathways cross the midline?
medulla
in pain processing, where do 2nd order neurons synapse?
thalamus
what are the 5 large subcortical nuclei that participate in the control of movement in the basal ganglia?
- caudate nucleus
- putamen
- globus pallidus
- subthalamic nucleus
- substantia nigra
where do dopamine cell bodies reside?
substantia nigra
what does the striatum consist of?
caudate nucleus + putamen
describe the direct pathway in the basal ganglia for movement
how can dopamine be inhibitory or excitatory?
depends on the receptor it activates — D1(E) or D2(I)
what are 4 important neurotransmitters in the basal ganglia? how do they interact to control movement?
1) GABA (throughout basal ganglia) (major inhibitory)
2) dopamine (projections from the SNc) (inhibitory or excitatory)
3) glutamate (from/to cortex and the subthalamic nucleus) (major excitatory)
4) acetylcholine (large interneurons in the neostriatum)
how does an increase in DA affect movement?
how is movement affected in parkinson’s?
- loss of 60-70% of the neurons in SNc
- less movement due to loss of dopamine
