Transcript The synapse.

The synapse.
Coined by Charles Sherrington, 1898
Eccles work
• See slide below
Two views of Eccles’ double-barrel electrode
Advantages of the double-barrel electrode.
The preceding slide was a drawing of the
electrode tips. Real tips of the two barrels
is not likely to be of the same length. The
drawing at the right is more likely to occur.
What this allows is to record differentially
where the longer electrode is intracellular
and the shorter electrode is extracellular.
This is how the axon hillock was shown to
be more sensitive than the rest of the
soma.
A. Stretch reflex for the knee (man or cat)
Circuit for understanding chemical synapses (Squires et.
al.)
A of previous slide
• The afferent neurons of the quadriceps muscles
make an excitatory connection with the motor
neurons innervating this same muscle group (the
extensor motor neurons). They also make an
excitatory connection with an interneuron. This
interneuron, in turn, makes and inhibitory
connection with the motor neurons innervating the
antagonist biceps muscles group (the flexor motor
neurons).
Idealized Experimental Set Up
Monsynaptic and disynaptic connection to ventral horn
cells (Squires et.al)
Excitatory Post Synaptic Potential (EPSP)
IS and SD effects by antidromic vs
orthodromic stimulation.
The principles of neural coding
• The primary coding mechanism of the nervous
system is , frequency code, that is to say the
greater the intensity of the stimulus the
greater the number of action potentials per
unit time (frequency) elicited in a sensory
neuron. Thus the greater the stretch (slide 6),
the greater the number of AP elicited in the
stretch receptors in a given interval and the
greater the number of EPSPs produced in the
motor neuron.
Types of summation
• The effects of activating multiple stretch receptors
and together (spatial summation) and the effects of
multiple EPSPs by activation of a single stretch
receptor (temporal summation).
• Both of these processes add algebraically to
depolarize the postsynaptic cell body to reach a level
at which an AP is generated.
Assume the following cell arrangement
Summation based on time (Squires et. al.)
(cont.)
Summation, spatial(cont.)
Assume the following stimulation of neuron 1 and 2 on
to a postsynaptic neuron (Squires, et. al)(cont.)
Two types of EPSP generated, fast EPSP and slow EPSP
(cont.)
Inhibitory Post synaptic Potential (IPSP)
Another Look at Summation
Inhibition is the lowering of the potential below the
resting membrane potential
The cell integrates all EPEPs and IPSPs. If the
sum of the potentials gets above threshold, an
AP is generated
Gap Junction = elctricall synapse
In the slide above look for the A and D
• The dendrite D pictures an axon A (to the left
of D) with a series of ovals that define a
chemical synapse.
• On the right of D arrows depict electrical
synapses (gap junctions).
Chemical synapse – to read the legend, change
the level of magnification
Five arguments for and against
chemical synapses
• 1) Conduction velocities are far to quick
for ordinary metabolic activity (against).
• Loew’s study with the two hearts
showing some substance transferred
from the first to the second heart to slow
the heart down – “Vaga-stoff”
• 2) When comparing orthodromic to
antidromic stimulation there is an irreducible
delay in the former and not the latter.
• Adherents of the electrical synapse have no
circuit of neurons, in real anatomy, that can
account for the irreducible delay.
• 3) Anatomically, where one can impale the
presynaptic side with electrodes and read the
postsynaptic change (neuromuscular
junction), there is no relationship between the
form, or magnitude of the presynaptic
potential relative to the post synaptic
potential. There need not be if it is chemical
change,
• There should be if there was an electrical
synapse
• 4) It is difficult to see how both excitatory and
inhibitory potentials are designed for the
same cell if the synapse is electrical.
• Different chemicals could be used for different
types of potentials needed.
• 5) the fourth arguments runs into Dales
hypothesis: If a neuron is sensitive to a
neurotransmitter it should make that
neurotransmitter.
Criteria necessary for a molecule to be considered a
neurotransmitter (Patton’s requirements)
• 1) A neurotransmitter must be synthesized by and
released from neurons. The presynaptic neuron must
contain a transmitter and the appropriate enzymes
needed to synthesize that neurotransmitter.
• 2) The substance must be released from
neuron terminals by the activity of the AP.
Further that released should be in an
identifiable chemical/pharmacological form.
• 3) A neurotransmitter should reproduce at the
postsynaptic cell the specific events (such as
changes in membrane properties) that are
seen after stimulation of the presynaptic
neuron.
• 4) the effects of the putative neurotransmitter
should be blocked by competitive antagonists
of the receptor for the transmitter in a dose
dependent manner. In addition, treatments
that inhibit synthesis of the transmitter
candidate should block the effects of
presynaptic stimulatation.
• 5) There should be active mechanisms to
terminate the action of the putative
neurotransmitter. Among such mechanisms
are uptake of the transmitter by the
presynaptic neuron or glial cell through
specific transport molecules, or alternatively
enzymatic inactivation of the chemical
messenger.
• The following slide show the schematic
representation of Patton’s criteria over a
symbolic synapse (form Squires et. al.).
• Make sure you increase the magnification
level and read the figure legend.
Patton’s Five Criteria in Action
• The following slide shows the 5 processes that
Patton requires for a substance to be
considered a neurotransmitter. Increase the
magnification such that you can read the
boxes within the picture.
Neurotransmitters bind to receptors on the
postsynaptic membrane: two types
• Ionotropic receptors: opens ion channels
• Metatropic receptors: activate G proteins
(binds guanosine phosphate [GDP], guanosine
triphosphate [GTP] and other guanine
nucleotides).
• If the neurotransmitter is the first messenger,
the G protein is the second messenger.
Ionotropic Ach receptor
Metatropic receptor (2nd messenger)
• Synthesis and degradation of acytlcholine next
slide
Acytylcholine
What acetylcholine excites
Two classes of monoamines
• Catecholamine neurotransmitters:
•
dopamine (subtypes D1, D2, D3, D4, D5)
•
epinephrine
•
norepinephrine
• Indoleamines neurotransmitters:
•
melatonin
•
serotonin
Synthesis of Epinephrine & Norepinephrine
Post synaptic effects of various agents