Topic 3: Neurotransmitters and psychopharmacology Flashcards
The life-cycle of a NT/steps in synaptic transmission:
1 Synthesis.
2 Storage.
3 Release.
4 Diffusion across the synaptic cleft.
5 Binding to receptor.
6 Release.
7 Inactivation by enzymes (e.g. acetylcholinesterase cleaves acetylcholine into acetate and choline OR reuptake.
8 With re-uptake, inactivation OR re-storage in synaptic vesicles.
neurotransmitter V neuropeptide V hormone
neuropeptides (or ‘neuromodulators) are a special kind of NT that are synthesized in the cell body
neuropeptides are released through the dendrites and soma walls and all parts of the cell, and need multiple activation’s to be released, and when one cell fires the surrounding ones are encouraged to do so, and it diffuses widely, its more similar to a hormone, a spilling. Does gene altering stuff and last 20mins or longer, more for long term behavioral changes, and things like thirst hunger
e.g. oxytocin, vasopressin, insulin, glucagon
neuropeptides do not get re-uptook they diffuse away (and these large molecules are hard to make, bug influxes can temporarily exhaust supplies)
NT synthesized and released from the axon terminal, released by a single AP, doesn’t diffuse widely (just to those directly ahead), doesn’t change the genes of others, is very fast
hormones are like radio signals, anyone tuned in can pick it up, NT are like a phone call, only goes to one phone line, and NP are like a zoom call, go to a big area but still select (goes to specific areas of the brain, whereas hormones can go anywhere blood can carry them)
Sherrington
After Cajal discovered seperate neurons,
Sherrington showed that internal communication of a neuron was different to the kind of communication going on externally (e.g neurotrasmitter stuff in the synapses) which certainly confirmed Cajals hypothesis
together these two nearly simultaneous discoveries are the fathers of neuroscience
Main function of glutamate, GABA, ACh, dopamine, norepinephrine/epinephrine serotonin
glutamate, excitation
GABA, inhibitory
ACh, mainly excitation
dopamine,
norepinephrine/epinephrine
serotonin
Sherrington
After Cajal discovered separate neurons,
Sherrington showed that internal communication of a neuron was different to the kind of communication going on externally (e.g neurotransmitter stuff in the synapses) which certainly confirmed Cajals hypothesis
together these two nearly simultaneous discoveries are the fathers of neuroscience
how did sherrington show there was different communication inside and outside
testing dog relex to leg flexion reflex
he tapped and measured time
they already knew axon transmission goes at 40m/s
but the response went at 15m/s
it must have been slowed by the slower process of synaptic transmission.
a reflex arc goes from sensory neuron (afferent) to intrinsic neuron (within the spine - doesn’t go to brain -he tested by severing the dogs spinal chord-) to efferent motor neuron.
those three passes slowed it down
what is temporal summation, how did sherrington figure it out, and how does it relate to EPSP ex pos syn pot
the threshold of excitation for a postsynaptic neuron might not be reached (and is quickly decayed) but many quick simulations can trigger it (pinching the dog many times quickly)
this is temporal summation
excitatory post synaptic potential is this, the graded polerisation (partial polerisation) which can either increase or decrease the chances of an action potential with more stimulation it could be depolarising (sooner to activate - excitatory) or hyperpolerising (harder to activate - inhibitory)
sherringtons student Eccles measured this with electrodes on axons
IPSI is inhibitory postsynaptic potential
spatial summation and eccles finding about direction of stimulation
many stim at different places needed to cause AP
Eccles found direction matters if its going away from the cell body triggering dendrites in that direction it may not trigger AP where the other direction triggering dendrites one by one in the direction of the soma would aid AP activation
both spatial and temporal summation are about multiple stim on one neuron
IPSP how it works biologically confirmed by newer physiological studies
how sherrington showed this in the oldem days
inhibitory post synaptic potential is acheived by opening cloride ion channels or potassium ion channels, hyperpolerising the cell
(Cl- goes inside making it more -, K+ goes outside making it more neg inside, faster than the sodium potassium pump can normally bring leaky K+ in to keep it at -70mV, so it goes to below that, hence inhibitory)
sherrington saw the dogs alternate muscles extending when the reflex muscles flexed (and also the other three legs doing the opposite, necessary for the dogs balance)
he suggested there must be something inhibiting those alternate muscles while the reflex muscles were getting activated
IPSP’s dont propergate along an axon like AP does, they decay over time and distance always
maths of the nerous system, EPSP and IPSP
AP gets triggered when the summation at the axon hillock reaches -55mV/-50mV (about 20mV difference from normal)
more than just the summation of ESPS minus IPSP determine AP’s
some summate more or less readily
some have constant AP flow and EPSP just speed it up and IPSP just slow it down
some have multiple inputs at different places closer/furthur from the cell body affecting results
its a complex symphony boolean logic (ridgid true false statements, if A fires or B fires C fires but only if not D etc)
how neurotrasmitters are related to EPSP and IPSP
NT attach to proteins on the postsynaptic terminal which triggers the opening of sodium cloride or potassium channels, hence beginging the EPSP or IPSP process.
propergating channels are voltage opened
terminal channels at NT opened
how neurotrasmitters are related to EPSP and IPSP
NT attach to proteins on the postsynaptic terminal which triggers the opening of sodium cloride or potassium channels, hence beginging the EPSP or IPSP process.
propergating channels are voltage opened
terminal channels at NT opened
calcium as a unique extracellular ion
Ca2(+) acts similarly to sodium outside the cell, but does a 2nd messenger system
AP opens voltage opened Ca2 channels
Ca+ enters cell within 1-2ms vesicles open EXOCYTOSIS (endocytosis is where the left over vesicle bits of membrane are re used)
calcium also binds with and activates enzymes
these impact 2nd messengers which change the structure and function of cells
exocytosis
NT leaving presynaptic button
the vesicle binds to the presyn membrance and splits open release the NT into the cleft
1 Synthesis.
neuropeptides (“peptide NT”) synthesized in the cell body requiring mRNA then transported via FAST axoplasmic transport
stored in dense core vesicles. released like hormones, diffused from everywhere
smaller molecule neurotransmitters are made in the button.
(pre-curses and things needed for vesicles still made in cell body and transported by SLOW axo to the terminal button, where the smaller molecules are made package and stored)
stored in clear core vesicles
2 Storage.
in vesicles (all but NO get stored) stored in the terminal buttons
- Release
AP causes calcium channels to open and influx into the cell near the button
calcium binds with protein causing vesicles to DOCK and create a fusion pore openin in the membrane, releases the NT out via diffusion
4 Diffusion across the synaptic cleft.
super fast, picked up by dendrites
5 Binding to receptor.
this is where the magic happens, could be excititory or inhibitory, binds to a receptor site on the dendrites, casuing the opening of its sodium (of cloride, potassium or calcium) channels
sodium excitatory
cloride inhibitory
potassium inhibitory (more goes out)
