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 (2 nd messenger)

Synthesis and degradation of acytlcholine next slide

Acytylcholine

What acetylcholine excites

Two classes of monoamines Catecholamine neurotransmitters: dopamine (subtypes D 1, D 2, D 3, D 4, D 5 ) epinephrine norepinephrine Indoleamines neurotransmitters: melatonin serotonin

Synthesis of Epinephrine & Norepinephrine

Post synaptic effects of various agents