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Department of medical physiology1st week
Semester: summer
Study program: Dental medicineLecture: RNDr. Soňa Grešová, PhD.
Department of medical physiology1st week
1. General neurophysiology
2. Central nervous system synapses
1. General neurophysiology
NS
CNSPNS
Sensory PNS Motor PNS
Specialsensation
General sensation
Somaticmotor responces
Autonomicmotor responces
Somaticsensation
Visceralsensation
- Vision- Smell- Taste- Hearing- Equilibrium - Skin
- pain- temperature- touch
- Locomotor system- joints- ligaments- tendons
BrainSpinal cord
- Dull pain- Distension
SANS PANS
1. General neurophysiology
• NS
1. Neurons
2. Neuroglial cells
- Supporting Cells of CNS
- Supporting Cells of PNS
1. General neurophysiology1. Neuron
• ~1011 nerve cells in human brain
• 3 Regions:
1. Soma (cell body)
2. Dendrites
- Extensions of the cell body that repeatedly divide
- Increase surface area for synaptic connections
3. Axon
- Terminal end branches into numerous synaptic boutons
- Allows one neuron to make many contacts
1. General neurophysiology2. Supporting Cells of CNS
• Glial Cells1. Astrocytes
- Star-shaped cells- Envelop capillaries forming the Blood-Brain
Barrier- Form scars after an injury
2. Oligodendrocytes- Produce myelin in CNS
3. Microglia- Become active due to inflammation or injury- Phagocytose cellular debris
1. General neurophysiology2. Supporting Cells of PNS
• Schwann Cell
- Perform basic functions that are accomplished by 3 types of glial cells in CNS
Central nervous system
• contains more than 100 billion neurons
• Incoming signals• single axon leaving the
neuron• the signal normally passes
only in the forward direction (from the axon of a preceding neuron to dendrites on cell membranes of subsequentneurons)
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Sensory part of the nervous system-Sensory Receptors
• The nervous system are initiated by sensory experience exciting sensoryreceptors
• This information enters the central nervous system through peripheral nerves and is conducted immediately to multiple sensory areas in
• 1) the spinal cord at all levels; • 2) the reticular substance of the
medulla, pons, and mesencephalonof the brain;
• 3) the cerebellum; • 4) the thalamus; and • 5) areas of the cerebral cortex
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Motor part of the nervous system—Effectors
• The nervous system is to control the various bodily activities:
• 1) contraction of appropriate
skeletal muscles throughout
the body,
• 2) contraction of smooth muscle in the internal organs,
• 3) secretion of active chemical substances by both exocrine and endocrine glands in many parts of the body
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Processing of information—“Integrative” function of the nervous system
• more than 99 per cent of all sensory information is discarded by the brain as irrelevant and unimportant(clothing, seat pressure)
• important sensory information excites the mind this channeling and processing of information is called the integrative function of the nervous system
• some synapses transmit signals from one neuron to the next with ease (facilitatory signal), whereas others transmit signals only with difficulty (inhibitory signal)
• the storage of information is the process we callmemory, and is a function of the synapses
Major levels of centralnervous system function
• 1) the spinal cord level, – neuronal circuits (after the spinal cord has been cut in the high neck
region) in the cord can cause:• 1) walking movements, • 2) reflexes that withdraw portions of the body from painful objects, • 3) reflexes that stiffen the legs to support the body against gravity, • 4) reflexes that control local blood vessels, gastrointestinal movements, or urinary
excretion
• 2) the lower brain or subcortical level, – medulla and pons (subconscious control of arterial pressure and respiration)– the cerebellum and the reticular substance of the medulla, pons, and mesencephalon
(control of equilibrium)– the medulla, pons, mesencephalon, amygdala, and hypothalamus (feeding reflexes, such
as salivation and licking of the lips in response to the taste of food)– the cerebral cortex (anger, excitement, sexual response, reaction to pain, and reaction to
pleasure)
• 3) the higher brain or cortical level– the cortex never functions alone but always in association with lower centers of the
nervous system– the cortex opens a world of stored information for use by the mind
Central nervous systemSynapses
• Synaptic functions of neurons
– each impulse:
• 1) may be blocked in its transmission from one neuron to the next,
• 2) may be changed from a single impulse into repetitive impulses,
• 3) may be integrated with impulses from other neurons to cause highly intricate patterns of impulses in successive neurons
Types of synapses—Chemicaland Electrical
• 1) the chemical synapses (neurotransmitter)– transmitter in turn acts on receptor proteins in the
membrane of the next neuron to excite the neuron, inhibit it, or modify its sensitivity in some other way
– e.g. acetylcholine, norepinephrine, epinephrine, histamine, gamma-aminobutyric acid (GABA), glycine, serotonin, and glutamate
– they always transmit the signals in one direction fromthe neuron = principle of one-way conduction : theneuron that secretes the transmitter substance, called the presynaptic neuron, to the neuron on which the transmitter acts, called the postsynaptic neuron
Types of synapses—Chemicaland Electrical
• 2) the electrical synapses
– are characterized by direct open fluid channels that conduct electricity from one cell to the next
– most of these consist of small protein tubular structures called gap junctions that allow free movement of ions from the interior of one cell to the interior of the next
– often transmit signals in either direction
Physiologic anatomy of the synapse
• Anterior motor neuron in the anterior horn of the spinal cord– the soma, which is the main body of the
neuron; – a single axon, which extends from the
soma into a peripheral nerve that leaves the spinal cord;
– the dendrites, which are great numbers ofbranching projections of the soma that extend as much as 1 millimeter into the surrounding areas of the cord
– synaptic knobs called presynaptic terminals lie on the surfaces of thedendrites (80-95%) and soma (5-20%) of the motor neuron• Excitatory presynaptic terminals• Inhibitory presynaptic terminals
• Neurons in other parts of the cord and brain differ from the anterior motor neuron (perform many differentfunctions) Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Presynaptic terminals
• Terminal knobs (boutons, end-feet, or synaptic knobs)
• Synaptic cleft• the transmitter vesicles with the
transmitter substance• the mitochondria (ATP) supplies the
energy for synethesizing new transmitter substance
• the postsynaptic neuron—excites if the neuronal membrane contains excitatory receptors, inhibits if the membranecontains inhibitory receptors
• The action potential causes a small number of vesicles to empty into the cleft
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Presynaptic terminals—role of Calcium ions
• the presynaptic membrane contains large numbers of voltage-gatedcalcium channels
• an action potential depolarizes thepresynaptic membrane, calcium channels open and allow large numbers of calcium ions to flow into the terminal, they bind with special protein molecules on the insidesurface (release sites), this binding in turn causes the release sites to open through the membrane, allowing a few transmitter vesicles to releasetheir transmitter into the cleft after each single action potential
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Action of the transmitter substanceon the postsynaptic neuron
• The membrane of the postsynaptic neuron contains large numbers of receptor proteins with twocomponents:– 1) a binding component (outward into
the synaptic cleft—here it binds the neurotransmitter)
– 2) an ionophore component (that passes all the way through the postsynaptic membrane to the interior of the postsynaptic neuron), two types:• 1) an ion channel that allows passage of
specified types of ions through the membrane
• 2) a “second messenger” activator that is not an ion channel but instead is a molecule that protrudes into the cellcytoplasm and activates one or more substances inside the postsynapticneuron
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Function of “Receptor proteins” Ionophore component
• 1) Ion Channels– 1) cation channels (sodium,
potassium, calcium ions)• A transmitter substance that
opens cation channels is called an excitatory transmitter
– 2) anion channels (mainly chloride ions, but also minute quantities of otheranions)• A transmitter substances that
open anion channels are called inhibitory transmitters
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Function of “Receptor proteins” Ionophore component
• 2) “second messenger” system - several types:– 1) G-proteins (components α, β, γ)
• 1. Opening specific ion channels through the postsynaptic cell membrane• 2. Activation of cyclic adenosine monophosphate (cAMP) or cyclic
guanosine monophosphate (cGMP) in the neuronal cell• 3. Activation of one or more intracellular enzymes• 4. Activation of gene transcription
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Excitatory or Inhibitory receptors in thepostsynaptic membrane
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
• Excitation– 1. Opening of sodium channels to
allow large numbers of positive electrical charges to flow to theinterior of the postsynaptic cell
– 2. Depressed conduction through chloride or potassium channels, or both
– 3. Various changes in the internal metabolism of the postsynaptic neuron to excite cell activity or, insome instances, to increase the number of excitatory membrane receptors or decrease thenumber of inhibitory membrane receptors
Excitatory or Inhibitory receptors in thepostsynaptic membrane
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
• Inhibition– 1. Opening of chloride ion
channels through thepostsynaptic neuronalmembrane
– 2. Increase in conductance of potassium ions out of theneuron
– 3. Activation of receptor enzymes that inhibit cellularmetabolic functions that increase the number ofinhibitory synaptic receptors or decrease the number of excitatory receptors
Chemical substances that functionas synaptic transmitters
• 1. small-molecule, rapidly actingtransmitters
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Chemical substances that functionas synaptic transmitters
• 2. large - moleculeof neuropeptides , slowly actingtransmitters
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Electrical events duringneuronal excitation
• Resting membrane potentialof the neuronal soma
• Non – conducting plasmamembrane (-65mV spinalmotor neuron, -90mV largeperipheral nerve fibers and sceletal muscle fibers)
• Ion transport• Selective permeability• Sodium-potassium pump
– Sodium (Na+) and Potassiumtransport direction and rate
– Imbalance of + ions Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Effect of synaptic excitation on the Postsynaptic Membrane— Excitatory postsynaptic potential,
Inhibitory postsynaptic potential
• The resting membranepotential everywhere in the soma is -65 millivolts
• The positive increase in voltage above the normal resting neuronal potential—that is, to a less negative value—is called the excitatory postsynaptic potential (or EPSP)
• An increase in negativity beyond the normal resting membrane potential level is called an inhibitory postsynaptic potential (IPSP).
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
1. General neurophysiologyAction potencial
• Stimulus-gated Na+ channels open allowing Na+ to diffuse in
• Voltage-gated Na+ channels open
• The membrane depolarizes even further
• AP peaks (+30mV) when voltage-gated Na+
channels close
• Repolarisation begins
• Brief hyperpolarization and return of ion channelsto resting
1. General neurophysiology Refractory period
• Absolute
• Relative
General neurophysiologyAction potential
Action potential
• Propagated (all or none)
• Always stereotypical
• Has no phenomenon of sumation
• All or none principle:
- Subtreshold – no AP
- Treshold - AP
General neurophysiologyNeural Synapses
• Spatial sumation
- increasing signal in greater numbers of
fibers (threshold for firing)
• Temporal sumation
- increasing frequency of nerve impulses in each fiber
Simultaneous summation of Inhibitory and Excitatory postsynaptic potentials
• if a neuron is beingexcited by an EPSP, an inhibitory signal from another source can often reduce the postsynaptic potential to less than threshold value for excitation, thus turningoff the activity of the neuron
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
General neurophysiologyNeural Synapses
• Facilitation
- membrane potential is nearer the threshold for firing then normal, but not yet at the firing level
- the neurons so that they can respond quickly and easily to signals arriving fromother sources
Decrement of electrotonic conduction in the dendrites— greater Excitatory (or Inhibitory) effect by
synapses located near the soma
• decremental conduction - isdecrease in membranepotential as it spreads electrotonically along dendrites toward the soma
– before the excitatory potentials can reach thesoma, a large share of the potential is lost by leakagethrough the membrane
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Relation of state of excitation of theneuron to rate of firing
• Different neurons respond differently, have differentthresholds for excitation, and have widely differingmaximum frequencies of discharge
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Fatigue of synaptic transmission
• when excitatory synapses are repetitively stimulated at a rapid rate, the number of discharges by the postsynaptic neuron is at first very great, but the firing rate becomes progressively less in succeeding milliseconds or seconds
The fatigue process:• 1) progressive inactivation of many of the
postsynaptic membrane receptors • 2) slow development of abnormal concentrations
of ions inside the postsynaptic neuronal cell