Physiology of synapses, Physiology of synapses, interneuronal connectionsinterneuronal connections

What is a synapse?What is a synapse?

A A synapsesynapse is the junction between 2 is the junction between 2 neurones.neurones.

A specialized junction that transfers A specialized junction that transfers

nerve impulse information between nerve impulse information between

neuronsneurons

A junction that mediates information transfer from one A junction that mediates information transfer from one neuron:neuron:– To another neuronTo another neuron

Called neuro-synapses or just synapseCalled neuro-synapses or just synapse

– To an effector cellTo an effector cell Neuromuscular synapse if muscle involvedNeuromuscular synapse if muscle involved Neuroglandular synapse if gland involveNeuroglandular synapse if gland involve

Presynaptic neuron – conducts impulses toward the Presynaptic neuron – conducts impulses toward the synapsesynapse

Postsynaptic neuron – transmits impulses away from Postsynaptic neuron – transmits impulses away from the synapsethe synapse

Two major types:Two major types:– Electrical synapsesElectrical synapses– Chemical synapsesChemical synapses

SynapsesSynapses

Anatomical Types of SynapsesAnatomical Types of Synapses

Axo-dendriticAxo-dendritic – synapses between the axon of – synapses between the axon of one neuron and the dendrite of anotherone neuron and the dendrite of another

Axo-somaticAxo-somatic – synapses between the axon of one – synapses between the axon of one neuron and the soma of anotherneuron and the soma of another

Other types of synapses include:Other types of synapses include:– Axo-axonicAxo-axonic (axon to axon) (axon to axon)– Dendro-dendritic (Dendro-dendritic (dendrite to dendrite)dendrite to dendrite)– Dendro-somaticDendro-somatic (dendrites to soma (dendrites to soma))

Functional classificationFunctional classificationor Types of comnicationor Types of comnication

A.Chemical synapseA.Chemical synapse Almost all synapses used for signal transmission Almost all synapses used for signal transmission

in the CNS of human being are chemical in the CNS of human being are chemical synapses.synapses.

First neuron secretes a chemical substance First neuron secretes a chemical substance called neurotransmitter at the synapse to act on called neurotransmitter at the synapse to act on receptor on the next neuron to excite it, inhibit receptor on the next neuron to excite it, inhibit or modify its sensitivity.or modify its sensitivity.

The chemical synapseThe chemical synapse is a specialized junction that is a specialized junction that transfers nerve impulse information from a presynaptic transfers nerve impulse information from a presynaptic membrane to a postsynaptic membrane using membrane to a postsynaptic membrane using neurotransmitters.neurotransmitters.

Axo-dendritic synapse Axo-somatic synanpse Axo-axonic synapseAxo-dendritic synapse Axo-somatic synanpse Axo-axonic synapse

The Chemical SynapseThe Chemical Synapse

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NeurotransmittersNeurotransmitters Properties of neurotransmitters:Properties of neurotransmitters:

1) synthesized in the presynaptic neuron1) synthesized in the presynaptic neuron

2) Localized to vesicles in the presynaptic neuron2) Localized to vesicles in the presynaptic neuron

3) Released from the presynaptic neuron under 3) Released from the presynaptic neuron under physiological conditionsphysiological conditions

4) Rabidly removed from the synaptic cleft by uptake or 4) Rabidly removed from the synaptic cleft by uptake or degradationdegradation

5) Presence of receptor on the post-synaptic neuron.5) Presence of receptor on the post-synaptic neuron.

6) Binding to the receptor elicits a biological response6) Binding to the receptor elicits a biological response

R.E.B, 4MedStudents.com, 2003

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Neurotransmitters found in the nervous system

EXCITATORY Acetylcholine Dopamine Histamine

Nonepinephrine Epinephrine Glutamate Serotonin

INHIBITORY GABA Glycine

TThe he SSynapseynapse

Structure of a synapseStructure of a synapse

Excitatory postsynaptic potentialExcitatory postsynaptic potential

Single stimuli applied to the sensory nerves Single stimuli applied to the sensory nerves in the experimental situation described in the experimental situation described above characteristically do not lead to the above characteristically do not lead to the formation of a propagated action potential formation of a propagated action potential in the postsynaptic neuron. Instead, the in the postsynaptic neuron. Instead, the stimulation produces either a transient, stimulation produces either a transient, partial depolarization or a transient partial depolarization or a transient hyperpolarization.hyperpolarization.

If positive ion gates open (which allow more If positive ion gates open (which allow more Na+ and Ca2+ to enter than K+ to exit), the Na+ and Ca2+ to enter than K+ to exit), the membrane becomes depolarized, which results in membrane becomes depolarized, which results in an excitatory postsynaptic potential (EPSP). If an excitatory postsynaptic potential (EPSP). If the threshold potential is exceeded, an action the threshold potential is exceeded, an action potential is generated.potential is generated.

If K+ or chlorine ion (Cl−) gates open (allowing If K+ or chlorine ion (Cl−) gates open (allowing K+ to exit or Cl− to enter), the membrane K+ to exit or Cl− to enter), the membrane becomes more depolarized (hyperpolarized), becomes more depolarized (hyperpolarized), which results in an inhibitory postsynaptic which results in an inhibitory postsynaptic potential (IPSP). As a result, it becomes more potential (IPSP). As a result, it becomes more difficult to generate an action potential on this difficult to generate an action potential on this membrane.membrane.

Summary of Synaptic

Transmission

Chemical SynapseChemical SynapseEvents at a chemical synapse1. Arrival of action potential on

presynaptic neuron opens volage-gated Ca++ channels.

2. Ca++ influx into presynaptic term.3. Ca++ acts as intracellular messenger stimulating synaptic vesicles to fuse

with membrane and release NT via

exocytosis.4. Ca++ removed from synaptic knob by mitochondria or calcium-pumps.5. NT diffuses across synaptic cleft and binds to receptor on postsynaptic

membran6. Receptor changes shape of ion

channel opening it and changing membrane

potential7. NT is quickly destroyed by enzymes

or taken back up by astrocytes or

presynaptic membrane.Note: For each nerve impulse reaching

the presynaptic terminal, about 300 vesicles are emptied into the cleft. Each vesicle contains about 3000 molecules.

NT affects the postsynaptic membrane potentialNT affects the postsynaptic membrane potential Effect depends on:Effect depends on:

– The amount of neurotransmitter releasedThe amount of neurotransmitter released

– The amount of time the neurotransmitter is The amount of time the neurotransmitter is bound to receptorsbound to receptors

The two types of postsynaptic potentials are: The two types of postsynaptic potentials are:

– EPSP – excitatory postsynaptic potentials EPSP – excitatory postsynaptic potentials

– IPSP – inhibitory postsynaptic potentialsIPSP – inhibitory postsynaptic potentials

Postsynaptic PotentialsPostsynaptic Potentials

Neurotransmitter binding to a receptor at Neurotransmitter binding to a receptor at inhibitory synapses: inhibitory synapses: – Causes the membrane to become more permeable to Causes the membrane to become more permeable to

potassium and chloride ions potassium and chloride ions – Leaves the charge on the inner surface more negative Leaves the charge on the inner surface more negative

(flow of K+ out of the cytosol makes the interior more (flow of K+ out of the cytosol makes the interior more negative relative to the exterior of the membranenegative relative to the exterior of the membrane

– Reduces the postsynaptic neuron’s ability to produce Reduces the postsynaptic neuron’s ability to produce an action potentialan action potential

Inhibitory SynapsesInhibitory Synapses

Electrical SynapsesElectrical Synapses Pre- and postsynaptic Pre- and postsynaptic

neurons joined by neurons joined by gap gap junctionsjunctions – allow local current to flow allow local current to flow

between adjacent cells. between adjacent cells. ConnexonsConnexons: protein tubes in : protein tubes in cell membrane.cell membrane.

Rare in CNS or PNSRare in CNS or PNS Found in cardiac muscle and Found in cardiac muscle and

many types of smooth many types of smooth muscle. Action potential of muscle. Action potential of one cell causes action one cell causes action potential in next cell, almost potential in next cell, almost as if the tissue were one cell.as if the tissue were one cell.

Important where contractile Important where contractile activity among a group of activity among a group of cells important.cells important.

The SynapseThe junction between two neurons is termed a synapse(synapsis = point of contact)

The narrow gap between the two neurons at the synapse is the synaptic cleft; the cleft is filled with extracellular fluid and spans an area of approximately 20 nm

A neuron that conducts impulses toward a synapse is called a pre-synaptic neuron

A neuron that conducts impulses away from a synapse is called a post-synaptic neuron

= synapse

The Synapse

synapticknob

axon terminal

mitochondrion

pre-synapticmembrane

synapticcleft

post-synaptic membrane (with receptors for neurotransmitter)

A single neuron may have many thousands of synaptic junctions on its dendrites and cell body

synaptic vesicle(contains neurotransmitter)

An action potential travels downthe axon of the neuron to the synaptic knob and depolarises

the pre-synaptic membrane

Events at the synapse

post-synapticmembrane calcium ions

in theextra-cellular

fluid

Voltage-gated calcium ionchannels open in the

pre-synaptic membrane

Calcium ions diffuseinto the synaptic knob

An action potential travels downthe axon of the neuron to the synaptic knob and depolarises

the pre-synaptic membrane

post-synapticmembrane

Voltage-gated calciumchannels open in the

pre-synaptic membrane

Calcium ions diffuseinto the synaptic knob

Events at the synapse

The uptake of calcium ions triggers the fusion of

the synaptic vesicles with the pre-synaptic membrane

Neurotransmitter is releasedinto the synaptic cleft

by EXOCYTOSIS

post-synapticmembrane

Voltage-gated calciumchannels open in the

pre-synaptic membrane

Calcium ions diffuseinto the synaptic knob

The uptake of calcium ions triggers the fusion of the synaptic vesicles with the pre-synaptic membrane

Events at the synapse

Neurotransmitter diffuses across the cleft

and binds to specific protein receptors embedded in the

post-synaptic membrane

receptors in the post-synaptic

membrane

Depolarisation of the post-synaptic membrane

post-synapticmembrane

Events at the synapse Neurotransmitter diffuses across the cleft and binds to specific

protein receptors embedded in the

post-synaptic membrane

Binding of neurotransmitter opens Na+ gates in the membrane and there is an influx of Na+ into the

post-synaptic neuron

sodium ions

An excitatory post-synaptic potential (EPSP) buildsup across the membrane

and if this reachesthreshold, an action

potential is triggered inthe post-synaptic neuron

Depolarisation of the post-synaptic membrane

post-synapticmembrane

Events at the synapse The neurotransmitter, acetylcholine,is hydrolysed by the enzyme acetylcholinesterase, which islocated at the surface of the

post-synaptic membraneFollowing activation of thepost-synaptic membrane,

neurotransmitter is removed from the synaptic cleft to enablefurther stimulation to occur

sodium ions

The neurotransmitter, noradrenaline, is actively

transported back intothe axon terminals

Unidirectionality

post-synaptic membrane (with receptors for neurotransmitter)

Unidirectionality describes the one-way transmission of nerve impulses between neurons

Neurotransmitter is stored and released only on the pre-synaptic

side of the synaptic cleft

This arrangement allows for the transmission of

impulses between neurons in one direction only

synaptic vesicle(contains neurotransmitter)

Receptors for neurotransmitter are only located on the

post-synaptic membrane

Inhibition occurs at synapses where transmitter

release results in the hyperpolarisation of the

post-synaptic membrane

During hyperpolarisation, the post-synaptic membrane

potential becomes more negative than its resting potential and

results from either the efflux of positive charge or the influx

of negative charge

The nature of the neurotransmitter determines

the response of thepost-synaptic membrane

OcclusionOcclusion On account of divergence one neuron may pass excitive On account of divergence one neuron may pass excitive

signals on the other neurons. Another neuron may excite signals on the other neurons. Another neuron may excite several neurons. But if from both neurons which is several neurons. But if from both neurons which is divergented excitement will be simultaneously the total divergented excitement will be simultaneously the total quantity of excited neurons will be decrease.quantity of excited neurons will be decrease.

Opposite inhibitionOpposite inhibition

Lateral inhibitionLateral inhibition If in a neurons' chain, which secure opposite inhibition If in a neurons' chain, which secure opposite inhibition

collaterals of axons of inhibition neurons form synaptic collaterals of axons of inhibition neurons form synaptic connection with neighboring excitive cells in these cells connection with neighboring excitive cells in these cells develop lateral inhibition develop lateral inhibition

Spatial summation

The adding together of EPSPs The adding together of EPSPs

generated simultaneously at generated simultaneously at

many different synapses on a many different synapses on a

dendrite.dendrite.

Two or more presynaptic inputs Two or more presynaptic inputs

are active at the same timeare active at the same time A space (spatial) dependent A space (spatial) dependent

process.process. Occurs in a Convergent SynapseOccurs in a Convergent Synapse

Temporal summationTemporal summation

The adding together of EPSPs The adding together of EPSPs

generated at the same synapse if generated at the same synapse if

they occur in rapid succession, they occur in rapid succession,

within 1-15 msec of one another.within 1-15 msec of one another.

The same presynaptic fiber fires The same presynaptic fiber fires

AP in quick successionAP in quick succession

A Time (Temporal) dependent A Time (Temporal) dependent

processprocess

Occurs in a Divergent SynapseOccurs in a Divergent Synapse