Download Synapses and Neurotransmitters

Synapses
synapses are the functional connection between neurons and a few other cells
(eg. muscles, glands)
CNS: neuron neuron
PNS:
neuron neuron
neuron muscle fiber [=neuromuscular junction]
neuron gland [=neuroglandular junction]
each neuron synapses with 1000 – 10,000 axonal terminals
10 Billion Neurons in NS 500 Trillion Synapses
presynaptic neuron vs postsynaptic neuron
two kinds of synapses:
1. electrical synapses
2. chemical synapses
1. Electrical Synapses
very common in embryonic brain,
much less common in adults;
get replaced by chemical synapses
cells are directly connected with each other
cytoplasm is continuous
impulses can go in either direction
eg. brain: rapid stereotyped eye movements
eg. rhythmic contractions of smooth muscle
eg. intercalated discs of cardiac muscle
chambers contract as single cells
2. Chemical Synapses
most common kind of synapse
actual gap or space between nerve cells
one direction only (= unidirectional)
prevents direct transmission of action potential
1
requires release of a chemical messenger =neurotransmitter
What Happens at Chemical Synapse:
1. AP travels down axon of presynaptic neuron to axonal end bulb
2. AP causes Ca++ gates to open and Ca++ enters presynaptic neuron
3. Ca++ activates enzymes in axonal end bulb which stimulates exocytosis of
neurotransmitter
[synaptic vesicles move to surface of cell and release NT]
4. NT diffuses across synaptic cleft
5. NT binds to specific receptor molecules in membrane of postsynaptic neuron
(dendrite or cell body)
6.
causes chemical gates to open allowing some ions in
can cause partial depolarization or hyperpolarization depending on gates
7. termination of NT occurs when:
a. it is degraded by enzyme on postsynaptic neuron or in synapse
b. it returns to presynaptic neuron and is reabsorbed
c. or it diffuses away from synapse
whole process takes 0.3 – 5.0 ms
Kinds of Chemical Synapses
Above is general idea of what happens at a synapse
There are different kinds of chemical synapses:
1. excitatory produce EPSP’s
2. inhibitory produce IPSP’s
1. Excitatory Synapses
NT binding causes partial depolarization of post synaptic membrane
Na+ and K+ ions diffuse simultaneously in opposite directions
but more Na+ in than K+ out
depolarization produces EPSP’s
2
lasts only a few milliseconds
then membrane returns to resting potential
2. Inhibitory Synapses
NT binding induces hyperpolarization of membrane:
becomes more permeable to K+ (out)
and/or more permeable to Cl- (in)
causes hyperpolarization
produces IPSP’s
Synaptic Interactions (Neural Circuits)
Remember, each postsynaptic neuron may synapse with 10,000’s of
presynaptic neurons (=neuronal pools)
some of these synapses are excitatory; some are inhibitory
sum of all EPSP’s and IPSP’s at a particular time determine whether
a neuron will generate an action potential or not
Summation:
1. Temporal summation
1 or more neurons transmit impulses in rapid sequence
2. Spatial summation
large # of terminals are stimulated at the same time
axonal hillock acts as a “bean counter”
it totals all the effects
may or may not trigger AP
Potentiation:
can also get potentiation (facilitation)
doesn’t fire but easier to fire next time.
Finally, there are literally 100’s of different kinds of
neurotransmitters;
some excitatory,
some inhibitory
bind to specific receptors in specific parts of nervous system
can produce a variety of effects on post synaptic neurons
3
also can get various additional modifications of synapse:
changes in the amount of NT released
changes in excitability of post synaptic neuron
presynaptic inhibition
neuromodulation
etc.
Neurotransmitters
neurotransmitters are the language of the nervous system
NT are released at chemical synapses
100’s have been identified
some are excitatory
some are inhibitory
the same NT may have different effects in different parts of body
eg. excitatory one place, inhibitory another
The effect of a NT on a postsynaptic neuron depends on
the properties of the receptor
not on the nature of the NT
some neurons produce and release a single NT
most make 2 or more and can release one or all
synapses in PNS release only a few different neurotransmitters
esp ACh, Epinephrine, NE
most of the diversity is in the CNS, esp the brain
a variety of different chemicals have been found to act as neurotransmitters:
1. acetylcholine
2. protein & amino acid derivatives
biogenic amines
amino acids
peptides
proteins
3. Inorganic gasses
4. ATP
Effects of Drugs on Nervous Transmission
4
Drugs generally interfere with key steps in synaptic transmission:
1. affect NT synthesis
2. alter rate of release
3. prevent binding to receptor
4. prevent NT inactivation
The end
1.
2.
3.
result of these actions:
drugs mimic specific neurotransmitters
enhance the actions of a NT
block action of NT
1. Drugs with general effects on Synapses
a. Dilantin
used to treat epilepsy
epilepsy a too rapid firing of certain brain
cells
subsides only when NT supply runs out
dilantin increases effectiveness of Na+ active transport to
stabilize resting potential
b. Caffeine
stimulant
generally lowers threshold at synapses
2. Acetylcholine (ACh)
1st to be identified
at all NM jcts
also found in autonomic NS at some smooth and cardiac muscles
generally has stimulatory effect on skeletal muscles
in autonomic NS may have stimulatory or inhibitory effect
in CNS:
1. inadequate amt ACh correlated with Alzheimer’s
2. ACh receptors destroyed in Myasthenia gravis, an autoimmune
disease
in PNS: Acetylcholine at NM Jcts
1. Botulism Toxin
blocks release of ACh paralysis
2. Black Widow Toxin
stimulates massive releases of ACh
intense cramping & spasms
3. Nicotine
mimics ACh binds to receptor and activates it but no
enzyme to remove it
5
prolonged hyper activity
4. atropine, curare
binds to receptor but does not induce muscle contraction
since ACh cannot bind to receptors already bound
to curare muscle cells cannot be stimulated to contract
paralysis
in most synapses, once ACh binds to receptor and
initiates a response it is removed by enzyme acetylcholinesterase
nerve gas, malathion (=Cholinesterase inhibitors)
blocks breakdown of ACh
extended, extreme contractions
3. Protein & Amino Acid Derivatives
broadly distributed in brain
affect behavior, moods, sleep, thought
some examples:
a. dopamine
a catecholamine
synthesized from tyrosine
esp in substantia nigra of basal ganglia
(midbrain)
affects coordination of skeletal muscles
also a “feel good” NT
1. Parkinson’s Disease
deficiency
tremors (no inhibition of basal nuclei)
2. schizophrenia
correlated with excess of dopamine
3. amphetamines
enhance its feel good effects
4. cocaine
blocks its uptake
b. norepinephrin
esp in brain stem
another “feel good” NT
affects mood: arousal, dreaming
also released by some neurons in autonomic
NS (sympathetic branch)
6
1. generally excess mania
deficiency depression
2. Cocaine & amphetamines
prevents inactivation of norepinephrin
enhances its effect
amphetamines and cocaine have similar effect
as on dopamine
c. serotonin
indolamine
syn from tryptophan or histidine
in brain stem (reticular system)
induces sleep, temp regulation, appetite,
affects mood and aggression
1. LSD
binds to serotonin receptors
prevents its effect or counteracts its
function in brainstem (RAS)
2. Prozac
prevents its uptake
relieves anxiety and depression
3. linked to migraine headaches
d. histamine
produced in hypothalamus
in immune system is powerful vasodilator
e. aspartate
amino acid
only in CNS
excitatory
f. glutamate
amino acid
only in CNS
excitatory
important in learning and memory
1. released in large quantities after stroke
increases damage to nervous tissue
g. glycine
amino acid
in spinal cord
inhibitory
7
strychnine blocks receptors
causes convulsions
h. GABA
modified amino acid
most abundant inhibitory NT in brain
(~1/3rd of all)
inhibits skeletal movements
1. deficiency: Huntington’s disease
jerky movements
2. alcohol
enhances its inhibitory effects
slowed reflexes
reduced coordination
also affects mood
excess:
less anxiety
deficiency: more anxiety
1. Valium
binds to GABA receptors
mimics or enhances its effects
less anxiety
i. Substance P
peptide (chain of amino acids)
mediates pain transmission in PNS
in CNS affects mood
also involved in respiratory and cardiovascular
control
j. endorphins & enkephalins
peptides
in limbic system and related structures
natural opiates
reduces pain perception
“runners high”
1. morphine, heroin, methadone
binds to enkephalin receptors
mimicks effecs of endorphins
k. cholecystokinin
peptide
8
may be related to feeding disorders
4. Inorganic Gasses
a. NO (nitric oxide)
toxic gas
short lived
is synthesized on demand
not stored in axonal vesicles
in CNS may be involved in learning and memory
in PNS causes relaxation of smooth muscle
b. CO (carbon monoxide)
in CNS
similar physiology as NO
5. ATP
now recognized as a major neurotransmitter in both CNS and PNS
produces fast excitatory response at certain receptors
Neuromodulators
other chemicals can be released at synapse in addition to neurotransmitters:
=neuromodulators
neuromodulators can influence the release of NTs or the post synaptic
neuron’s response to the NT
NM are usually peptides = neuropeptides
a chemical may be both a NT and NM
neuromodulators function in 3 different ways:
1. have direct effect on membrane potential by opening and closing
chemical gates
2. have indirect effect on membrane potential thru “second messenger”
eg. receptor on cm
adenylate cyclase
cyclic AMP
3. gasses are lipid soluble and diffuse into post-synaptic cell to activate
enzymes and second messengers
9