Nervous System -1

Chapter 10Nervous SystemHuarong YuDepartment of Physiology,Chongqing Medical University

Section A Structure and function of neurons

The nervous system

Nerve cells and astrocytes

Neuronneuroglia

Structure and maintenance of neuronsSomaAxonDendrites AxonProcesses

Functional of Neuronal Compartments Dendrite receive and integrate the information Soma receive and integrate the information Axon conducts signals from the cell bodyAxon terminal transmits signals (releases neurotransmitters) from the neuron to other cells

The main function of neuron is to receive, integrate and transmit the electrical signals which carries information.

A typical motoneuron at the anterior horn of spinal cord

According to the numbers of processes Unipolar neuron, bipolar neuron, multipolar neuronClassification:

According to the function of neurons Sensory neuron, motor neuron, interneuron(99%)According to the released transmitters Cholinergic neuron, adrenergic neuron

Nerve fibers:Nerve fiber refers to axon and its sheath or neurilemma. There are myelinated fiber and unmyelinated fiber. They transmits the action potential or excitation.

Action potential propagationSaltatory conduction

Local current flow

Characteristics of Action Potential PropagationIntegrityInsulation (connective tissue, electrolytical solution)Propagation in two directions Relatively non-fatigue (less energy consumption, no transmitter exhaustion ).

Nerve fiber types and function

Fiber type Function Fiber diameter (m)Conduction velocity(m/s)Spike duration(ms)Absolute refractory period (ms)A Proprioception;somatic motor12-2070-120

0.4-0.5

0.4-1 Touch, pressure5-1230-70 Motor to muscle spindle3-615-30 Pain, cold, touch 2-512-30BPreganlionic autonomic 33-151.21.2C Dorsal root Pain, temperature, some mechanoreception, reflex responses 0.4-1.21.5-222SympatheticfiberPostganglionic sympathetic nerve0.3-1.30.7-2.322

Numerical classification used for sensory neurons

NumberOriginFiber Type IaIbMuscle spindle, annulospiral ending, Golgi tendon organ A AIIMuscle spindle, flowerspray ending, touch,pressureAIIIPain and cold receptors; some touch receptorAIVPain, temperature, and other receptorDorsal root C

Nerve fibers - Axoplasmic Transport Secretary granuleMitochondria

Section 2 neuroglia and its function classification PNS

Neuroglia and its function classification CNS

CNS

Characteristic of NeurogliaNeuroglia has processes, but no dendrites and axon.

There is no synapses, but gap junction.

There is changes of membrane potential, but no APs.

The function of neurogliaSupport the neuron: There is no connective tissue in CNS. The space is filled with astrocytes. Their long processes forms network to support neurons bodies and fibers.

2. Transport of substance and trophic action (astrocytes) astrocytes connect neuron and capillaries by processes and secret neurotrophins. 3. Insulation and barrier effect. (astrocytes)

4. Stable the extracellular K+ concentration. (astrocytes)

Epilepsy

5. Take part in the metabolism of some transmitters et al (intake, synthesis and secretion)6. Take part in the immunologic response mononuclear phagocyte system Antigen presenting cell: astrocytesMicroglial cells can be turned into phagocytes

7. Microglia clear the debris of neuronal tissue; astrocytes regenerate to replace the dead neurons.8.Oligodendrocytes form the myelin sheath by wrapping their processes around the axon.

Section B Synapses

Synapse is the specialized contact zone between neurons, where informations are transmitted from one neuron to another. the chemical synapsesthe electrical synapsesSynapsesClassification of synapses:

1.Electrical Synaptic transmissionAdjacent cells are electrically coupled through a channel.Examples:Smooth and cardiac muscle.Intermedia: local current

Electrical SynapseGap Junction=2 ConnexonsA connexon is made of 6 subunits (connexin)A connexon is semi-channel

Electrical SynapseSix connexin molecules form a poreIons and small molecules can pass in both directions through these channelsNo synaptic delay in transmission of current from cell to cell. Allows synchronization of many cells quickly

2. Chemical transmissionIntermedia: transmitters Synaptic chemical transmissionNon-Synaptic chemical transmissionStructureNot 1:1Diffusion distance

(1)CHEMICAL SYNAPSEA.Functional anatomy of chemical synapsesPresynaptic terminal (synaptic knob) synaptic cleftpostsynaptic membrane.

Anatomy of the synapse Presynaptic terminal that contains transmitter vesicles, mitochondria and voltage-gated calcium channelSynaptic cleft: a space between the presynaptic and postsynaptic endings. It has a width of 200-300 which is filled with extracellular fluids.3. Postsynaptic terminal that contains receptor proteins for neurotransmitters

Synapses-structure

small, clear synaptic vesicles that contain acetylcholine, glycine, GABA or glutamatesmall vesicles with a dense core that contain catecholamines large vesicles with a dense core that contain neuropeptides Synapses-structure

Classification of Chemical synapsesAxo-axonicAxo-dendriticAxo-somatic

synaptic transmissionAP at terminalsDepolarization of presynaptic membraneVDCC opensCa2+ influx movement of synaptic vescles Neurotransmitter release NT+receptor Opening of channels Changes of MP of postsynaptic neuronIt is a kind of electro chemo electro processes

Postsynaptic potential

Excitatory postsynaptic potentials (EPSP)

Inhibitory postsynaptic potentials (IPSP)

Excitatory postsynaptic potentials (EPSP)Na+, K+ , Ca2+

Inhibitory postsynaptic potentials (IPSP)Cl-, K+ , Na+, Ca2+

Na+Na+Ca2+Ca2+K+K+Slow EPSP

Na+Na+Ca2+Ca2+-70mVSlow EPSPK+K+xxSlow EPSP

Na+Na+Ca2+Ca2+Slow IPSP

Na+Na+Ca2+Ca2+K+K+Slow IPSP

Slow IPSPNa+Na+Ca2+Ca2+-70mVSlow IPSPK+K+

Summary of synaptic potentialsFast EPSPsIonotropic receptor opens Na+ channelsSlow EPSPsMetabotropic receptor closes K+ channelsFast IPSPsIonotropic receptor opens Cl- channelsSlow IPSPsMetabotropic receptor opens K+ channels

There are slow EPSP and slow IPSP, the latent period is around 100 -500 ms. The mechanism is related to the changes of K+ conductance. The excitation or inhibition of the postsynaptic neuron depends on the summation of postsynaptic potentials.

Presynaptic Processes /Postsynaptic Processes

Properties of the EPSP and IPSPThey are local potential(local responses);they possess all characteristics common for the local potentials:A.They are not all or none,but graded in magnitude.B.They can only passively(electrotonically) propagate along the cell for a short distance.the magnitude reduces rapidly with the increase in distance.C.They do not produce a refractory period,so that they can summate in a single cell.

3.Characteristics of chemical synaptic transmission Several distinct features exist in the synaptic transmission as compared with the conduction of the nerve fibers.

One-way conduction Synapses generally permit conduction of impulses in one direction only, from presynaptic to the postsynaptic neuron.

Synaptic delay1 synapse: 0.3-0.5msMultisynapse: 500ms

Summationspatial and temporal summation

Electrical StimulatorABBC-70 mVSpatial Summation

10 20 30 40 50 60Stimulate Neuron A only.Membrane Potential in Post Synaptic Neuron

10 20 30 40 50 60Stimulate Neuron B only.Membrane Potential in Post Synaptic Neuron

10 20 30 40 50 60Spatial SummationStimulate Neuron A and B simultaneouslyMembrane Potential in Post Synaptic Neuron

4-4synapses firing8-8synapses firing16-16synapses firing

Temporal SummationAdding together of EPSPs generated by firing of the same presynaptic terminal at high frequency to generate an action potential in the postsynaptic neuron.

10 20 30 40 50 60Membrane Potential in Post Synaptic NeuronStimulate Presynaptic Neuron every 20 msec

10 20 30 40 50 60Membrane Potential in Post Synaptic NeuronTemporal SummationStimulate Presynaptic Neuron every 5 msec

Susceptibility. Since the resynthesis of the transmitter substance is dependent on metablic processes, the synapse is more sensitive than the nerve fiber to asphyxia and ischemia.

Fatigue

The fatigue of synaptic transmission may be due to exhaustion of transmitters.

Inhibition and facilitation at synapsesSection 1 Synapses - synaptic transmissionInhibitory interneuronAxo-axonal synapse

postsynaptic inhibition: Inhibitory interneurons release inhibitory transmitter which induces IPSPAfferent collateral inhibitionRecurrent inhibitionSection 1 Synapses- synaptic transmission

Afferent collateral inhibition This type of circuit is characteristic for controlling all antagonistic pairs of muscle.

Knee reflex

Recurrent inhibitionThis type of circuit is also important in preventing overactivity in many parts of the brain. Renshaw cell

Presynaptic InhibitionABACB

Presynaptic Inhibition-Mechanism Axon B release GABA + GABAA receptor in the Axon ACl- conductance the size of action potential in Axon A Ca2+ entryamount of excitatory neurotransmitter releasing from Axon AEPSP in the motor neuron

Presynaptic InhibitionGABAB receptors are also present and mediate presynaptic inhibition via a G protein that produces an increase in K+ conductance. this allowing a large number of K+ efflux out. Ca2+ entryOther transmitters also mediate presynaptic inhibition by G protein-mediated effects on Ca2+ channels and K+ channels.

Presynaptic Inhibition Presynaptic inhibition occurs in many of the sensory pathways in the nervous system. That is, adjacent terminal nerve fibers mutually inhibit one another, which minimizes the sideways spread of signals in sensory tracts.

postsynaptic facilitationEPSP

Presynaptic facilitationCentral facilitation:

Presynaptic FacilitationAxo-axonalExcitatory synapse

AB

Axon B release serotonin + 5-HT receptor in the Axon AcAMP K+ channel close (slow repolarization) the duration of action potential in Axon A Ca2+ entryamount of excitatory neurotransmitter releasing from Axon A EPSP in the motor neuron

1. Release and clearance of transmitters The amount of released transmitter depends on the amount of influxed Ca2+; presynaptic receptor; proteins related to docking.

Factors that influence synaptic transmission

2. Influence postsynaptic receptors: Upregulation and downregulation of numbers and affinities of postsynaptic receptors; Foreign substances that enter into synaptic cleft (Antagonist, blocker or agonist). Tubocurarine, -bungarotoxin

Non-synaptic chemical transmission

Non-synaptic chemical transmissionThere are no recognizable postsynaptic specializations. The multiple branches of the noradrenergic are beaded with enlargements, they are called varicosities, which contain neurotransmitters. Varicosity permits one neuron to innervate many effector cells.

Differences :

Section 2 transmitters and receptors-tranmittersConcept: Neurotransmitter is the chemical substances released from presynaptic terminal(neurons) and that mediates the signal transmission between two neurons or between neuron and cell.

Section 2 transmitters and receptors-tranmittersCriteria for identification: 1. There exists a system in the pre-synaptic neuron synthesizing the pre-cursors of transmitter and enzymes 2. Transmitter must be stored in the vesicle and released when terminal becomes stimulated and the release must be calcium-dependent

Section 2 transmitters and receptors-tranmittersCriteria for identification: 3. The transmitter released must act on the receptor in the postsynaptic membrane and external application of transmitter to postsynaptic neurons or nearby neurons can exert the same effect as natural released transmitter does

Section 2 transmitters and receptors-tranmittersCriteria for identification:4. There exists mechanisms by which the transmitter substances are inactivated , such as enzymatic degradation and reuptake

5. There exists special agonists and antagonists for the receptors which can mimic or block the action of transmitter

Section 2 transmitters and receptors-tranmittersClassification of neurotransmitters:Small molecule, rapidly acting transmitters:cause most of the acute responses of nervous system

neuropeptides , slowly acting transmitters or growth factors: cause more prolonged actions

Section 2 transmitters and receptors-tranmittersClassification of neurotransmitters:

Class I: Acetylcholine Class II: Norepinephrine Epinephrine Dopamine Serotonin HistamineClass III: Amino Acids Gama-aminobutyric acid (GABA) Glycine Glutamate AspartateClass IV Nitric oxide (NO)Small molecules

Section 2 transmitters and receptors-tranmittersClassification of neurotransmitters:

NeuropeptidesHypothalamic-releasinghormonesThyrotropin-releasing hormone (TRH)Luteinizing-releasing hormone(LRH)SomatostatinPeptide that act on gut and brainGastrin, sustance P,CCK etcFrom other tissueAngiotensin etcPituitary peptidesAdrenocorticotropic hormone (ACTH)Beta-endorphinAlpha-melanocyte-stimulating hormone ProlactinLuteinizing hormoneThyrotropinGrowth hormoneVesopressinOxytocin

Section 2 transmitters and receptors-receptorsConcept of receptor: The specific protein molecules in the cell membrane that can specifically bind with hormones or transmitters and induce trans-membrane signal transduction.

Section 2 transmitters and receptors-receptorsConcept:The substances that bind with receptors and cause the same effect as transmitters do are called agonist.The substances that bind with receptors but block the action are called antagonist.Both of them are called ligand.

Section 2 transmitters and receptors-receptorsConcept:Receptors located in the presynaptic membrane is known as presynaptic receptor. Presynaptic receptor usually modulates the release of transmitter from the presynaptic terminals.(adrenergic 2 receptor)Receptors located in the postsynaptic membrane are called postsynaptic receptors. Postsynaptic receptor mediates the transmission of information.

Section 2 transmitters and receptors-receptorsClassification:Ionotropic receptors are chemically-gated ion channels. When ligand binds with ionotropic receptors, the channels open and allow the ions to diffuse through the membrane, causing the membrane potential to alter

Section 2 transmitters and receptors-receptorsClassification:Metabotropic receptor is the receptor that signals through G-protein. So the receptor is called G-protein coupled receptor too.

ReceptorsIonotropicChemical-gated ion channel MetabotropicG-protein coupled receptor Directly coupled to ion channelsIndirectly coupled to ionchannelsFast effects (msec)Not so fast (100msec-sec)Several subunits (4-5)1 SubunitnAChmAChGABAAGABABGlycineDopamineGlutamate (AMPA/NMDA)Peptides5-HT35-HT*AspartateAdrenergic receptor

Section 2 transmitters and receptors-receptorsRegulation of receptors:Up-regulation: The number of receptor or the affinity of receptor for the transmitters increaseDown-regulation: The number of receptor or the affinity of receptor for the transmitters decrease

Section 2 transmitters and receptors- neurotransmitters and their receptors systemsAcetylcholine Amines Norepinephrine Dopamine Serotonin Amino acids Neuropeptide: opioid peptidesPurinergic transmittersOthers

Cholinergic system:Section 2 transmitters and receptors-transmitter and receptor systemmetabolism

Cholinergic system:Section 2 transmitters and receptors-transmitter and receptor systemN2N1Distribution PNSM

Cholinergic system:Section 2 transmitters and receptors-transmitter and receptor systemMotor nerve fibers that innervate skeletal muscles (neuromuscular junction)

All preganglionic autonomic nerve fibers

Most postganglionic parasympathetic endings

A few postganglionic sympathetic endings: sweat gland and muscle vasodilator endings

Cholinergic system:Section 2 transmitters and receptors-transmitter and receptor systemDistributionNeurons from specific projection system at thalamusReticular formation of brain stemBasal gangliaArea related to learning and memory (limbic system)Sensation, movement, learning and memory

Cholinergic system:Section 2 transmitters and receptors-transmitter and receptor systemDistribution of receptorsN type receptors: N1, N2M type receptors: M1-M5N2N1M

Cholinergic system:Section 2 transmitters and receptors-transmitter and receptor systemPhysiologic effects Muscarine-like action:Inhibition of cardiac activity; constriction of smooth muscle of bronchus, GI tract, bladder(detrusor), pupil, secretion of digestive glands; vasodilation. Muscarine is an agonist for cholinergic M-receptor Atropine is an antagonist for M- receptor GI tract convulsion

GiAC cAMP PKA Ca 2+(M2)

GqPLC IP3+DGCa2+(M1, M3, M4, M5)

Cholinergic system:Section 2 transmitters and receptors-transmitter and receptor systemPhysiologic effects Nicotine-like action: Stimulation of postganglionic neuron; constraction of skeletal muscles; Nicotine is an agonist for N-type (N1 and N2) receptorTubocurarine is an antagonist for N-type (N1 and N2) receptorHexamethonium is an antagonist of neuronal type receptorDecamethonium is an antagonist of muscle-type receptor.Sarin, organophosphorus poisoning

Amines-norepinephrine: metabolismSection 2 transmitters and receptors-transmitter and receptor system

Section 2 transmitters and receptors-transmitter and receptor systemReticular formation of mesencephalonLocus ceruleus of ponsReticular formation of medulla projection nerve fibers from these neurons has ascending parts,descending parts and parts innervating lower brain stemAmines-norepinephrine:distribution CNSawakeness, sleeping, emotion

Section 2 transmitters and receptors-transmitter and receptor systemNorepinephrine is secreted by most sympathetic postganglionic endings. Epinephrine, which is norepinephrine methyl derivative, is secreted by the adrenal medulla. By far it is not found that the postganglionic sympathetic endings secret epinephrine. Amines-norepinephrine:distribution PNS

Section 2 transmitters and receptors-transmitter and receptor systemreceptor: 1, 2 receptor: 1, 2, 3Affinity of NE with receptors: > NE+ excitable effectNE+ 1 excitable effectNE+ 2 inhibitory effectAmines-norepinephrine: receptors

Section 2 transmitters and receptors-transmitter and receptor systemAmines-DA:Nigra, striatumLimbic system at midbrain Tuberomammillary

Section 2 transmitters and receptors-transmitter and receptor systemAmines-DA: receptors (metabotropic receptor)D1-D5It is related to movement, emotion, endocrine and cardiovascular activity.

Section 2 transmitters and receptors-transmitter and receptor systemAmines-5-HT:Gastrointestinal tractnuclei of median raphe Various functions

Section 2 transmitters and receptors-transmitter and receptor systemAmines-Histamine:tuberomammillary nuclei Arouse, sexual behavior, endocrine,BP, pain sensation, drink

Section 2 transmitters and receptors-transmitter and receptor systemAminoacids Glutamate, aspartate(E) GABA,glycine(I)Metabotropic receptor: GP-PLC-IP3/DG-cAMPIonotropic receptor: KA/AMPA/NMDA receptor

Section 3 reflex-generals Classification:

Conditioned reflexA conditioned reflex is a reflex response to a stimulus that did not previously elicit the response, and is acquired by repeatedly pairing the stimulus with another stimulus that normally does produce the response. Unconditioned reflex

Section 3 reflex-generals

Unconditioned R Conditioned R exist after birth developed several unlimited number fixed form changeable centers below cortex cortex

Section 3 reflex-generals Structure basis:

Section 3 reflex-generalsMonosynaptic reflex: one synapse between afferent neuron and efferent neuron

Section 3 reflex-generalsPolysynaptic reflex:One or more than one interneuron in reflex arc

Section3 reflex-connetion of neuron in CNSDivergent connectionConvergent connectionChain connectionRecurrent connection

Divergent connection

Convergent connection

Chain CircuitRecurrent CircuitNegative feedbackPositive feedback(after discharge)

chapter 3 sensory function Section 1 somatic and visceral sensation Section 2 vision Section 3 hearing Section 4 sense of balance Section 5 taste and smell

Section 1 somatic and visceral sensation-final common pathways of the somatosensation1. The dorsal column system

2. The anterolateral systemspinothalamic tract (anterior and lateral STT)

1st order neurones The signals of dorsal-column, after entering the spinal cord from the dorsal spinal roots, ascend in the same side of spinal cord 2nd order neurones then, after the signals synapse and cross to the opposite side in the medulla, they ascend through medial lemnicus 3rd order neuronsFurther integration in the thalamus & 3rd order neurones project to the cortex.Dorsal column system

1st order neurones The signals of anterolateral systemafter entering the spinal cord from the dorsal spinal rootssynapse in the dorsal horns of the spinal gray matter 2nd order neurones then the signals cross to the opposite side of the cord and ascend through the anterior and lateral white columns of the cord 3rd order neurons Further integration in the thalamus & 3rd order neurons project to the cortex.Anterolateral system

Visceral sensation

Thalamus-generals:All sensory signals are transmitted to the thalamus except for the smell signal.Usually, the second-order neurons terminate at the third-order neurons in the thalamus. Therefore, thalamus is the principal relay station for sensory impulses that reach the cerebral cortex from the spinal cord, brain stem, cerebellum and other parts of the cerebrum.Section 1 somatic and visceral sensation-final common pathways of the somatosensation

Thalamus-generals:Section 1 somatic and visceral sensation-final common pathways of the somatosensation

Thalamus-classification of nuclei:Section 1 somatic and visceral sensation-final common pathways of the somatosensation Group I Specific sensory relay nuclei the nuclei receive direct projections from the second-order neurons and project to the sensory area of the cortex

Group I Specific sensory relay nuclei the medial geniculate body relays auditory impulses the lateral geniculate body relays visual impulses the ventral posterolateral nucleus relays impulses of somatic sensations from the body the ventral posteromedial nucleus relays impulses of somatic sensations from the head and faceVPMVPL

Thalamus-classification of nuclei:Section 1 somatic and visceral sensation-final common pathways of the somatosensationGroup II (associated nuclei):The nuclei receive nerve fibers from group I nuclei and other subcortical center and project to specific area of cerebral cortexthe anterior nucleus which receive afferents from the hypothalamus mammillary bodies and project to the limbic cortex is concerned with visceral function;

the ventral lateral nucleus which receives impulses from the cerebellum, basal ganglia and VP, and project to motor cortex is concerned with motor function.Section 1 somatic and visceral sensation-final common pathways of the somatosensation the pulvinar nuclei which receives impulses from LGB and MGB project to association area for specific sensation.

Thalamus-classification of nuclei:Section 1 somatic and visceral sensation-final common pathways of the somatosensationGroup III (intralaminar nuclei; non-specific projection nucleus):The nuclei receive nerve fibers from reticular formation of brain stem and projects diffusely to widespread areas of the cortex through multiple synapses. It plays a key role in maintaining the awakening or excitability of the animal

Sensory projection systems1. Specific projection system Both the group I nuclei project to the specific sensory area of the cortex in a way called point to point projection. The specific projection system makes synapse with large pyramidal cells in layer IV. Its function is to induce excitation, specific sensation and induce the cortex to send output signals.Section 1 somatic and visceral sensation-final common pathways of the somatosensation

2. Non-specific projection system This system is the group III nuclei which receive the indirect projections (multiple synapses) from the reticular formation of brain stem which receives the collaterals from the second-order neurons, and project diffusely to the widespread areas of the cortex via multiple synapses. It loses function of specific sensation. But it keeps the arousal and excitability of the cortex which is essential for the induction of specific sensation of cerebral cortex.Section 1 somatic and visceral sensation-final common pathways of the somatosensation

Sensory projection system

Specific projection system Nonspecific projection system Causes specific sensekeeps the arousal and excitability of the cortexPoint to point projectionNot point to point projectionSpecific and association thalamic nucleiNonspecific thalamic nucleiSpecific projection system causes the specific sense and response which require the wakefulness of the cortexThe collaterals of specific system provide the excitatory signals when it courses through the reticular formation of the brain stem

Ascending Reticular Activating System Stimulation of reticular formation of the mesencephalon awakens the animals and electroencephalogram(EEG) shows the asynchronous fast waves. Conversely, section of reticular formation at the rostral end causes the animals to sleep deeply and EEG shows the synchronous slow waves.

These two experimental results demonstrate that there is an ascending system in the reticular formation in the mesencephalon which arouse the the cortexascending reticular activating System. Destruction of this system, the animal comes to dope off. Ascending Reticular Activating System

Somatosensory cortex: Section 1 somatic and visceral sensation-neuronal pathways of the somatosensory system1. primary somesthetic sensory area somatic sensory area I somatic sensory area

Representations of the different parts of the body in separate regions of Somatic sensory area I

Somatosensory cortex: Section 1 somatic and visceral sensation-neuronal pathways of the somatosensory systemCharacteristics of somatic sensory area I1) Each side of the cortex receives sensory information exclusively from the opposites side of the body (with the exception of a very small amount of sensory information from the same side of the face)2) The size of the representation area is related to sensitivity of the area of the body (the size of these areas is directly proportional to the number of receptors in the area3) The head is represented in the most lateral portion of somato-sensory area I and the lower part of the body is represented medially.

Somatosensory cortex: Section 1 somatic and visceral sensation-neuronal pathways of the somatosensory systemCharacteristics of somatic sensory area II Very little is know about the function of somatosensory area II and localization is between precentral gyrus and insula. It maybe is related to pain sensation, if this area is damaged, there is no sensory disturbance.

Section 1 somatic and visceral sensation- sensation and receptorsClassification: Touch-pressure sensation thermal sensation Pain sensation Proprioception

Section 1 somatic and visceral sensation-somatic sensationPain sensation: Perception of pain is important for protecting the body from injury

Section 1 somatic and visceral sensation-somatic sensationPain sensation:Classification: fast pain and slow pain Fast pain is felt within about 0.1 second after a pain stimulus is applied, and is also described by alternative names, such as sharp pain, pricking pain, acute pain, and electric The fast pain always occur in skin and is not felt in most of deeper tissues pain of the body.

Section 1 somatic and visceral sensation-somatic sensationPain sensation:Classification: fast pain and slow pain Slow pain begins only after 1 second or more and then increases slowly over many seconds and sometimes even minutes. It is also known as slow burning pain, aching pain, throbbing pain, chronic pain, nauseous pain. It can occur both in the skin and almost any deep tissue or organ.

Dual transmission of pain signals into the CNSPeripheral pain fibers fast and slow fibers1. The fast-sharp pain signals in the peripheral nerves are transmitted to the spinal cord by small type A fibers at velocities between 6 to 30m/sec.2. Slow-chronic type of pain is transmitted by type C fibers at velocities between 0.5 and 2m/sec

Dual pain pathways in the cord and brain stem the neospinothalamic tract:fast pain

the paleospinothalamic tract: slow pain

The neospinothalamic tract A few fibers of the neospinothalamic tract terminate in the reticular areas of brain stem, but most pass all the way to the thalamus terminating in the ventral posterior nuclei. From these thalamic areas, the signals are transmitted to other basal areas of the brain and to the somatosensory cortex.Dual pain pathways in the cord and brain stem

Dual pain pathways in the cord and brain stemThe paleospinothalamic tract This pathway terminates widely in the brain stem. Only one tenth to one fourth of the fibers pass all the way to the thalamus. In stead, they terminate principally in the reticular system, which projects to the midline and intralaminar nonspecific projection nuclei of the thalamus and from there to many different parts of the cortex.

The fast-sharp type of pain can be localized much more exactly in the different parts of the body than can slow- chronic pain.Dual pain pathways in the cord and brain stem

Because of double system of pain innervation, a sudden painful stimulus often gives a double pain sensation: The sharp pain apprises the person rapidly of a damaging influence and therefore, plays an important role in making the person react immediately to remove himself or herself from the stimulus. Dual transmission of pain signals into the CNS

The slow pain tends to become greater over time and even gives one the intolerable suffering of long continued pain and makes the person continue to try to relieve the cause of the pain.Dual transmission of pain signals into the CNS

Section 1 somatic and visceral sensation-somatic sensationPain sensation:Receptor: Pain receptors are free nerve endings that are widespread in the superficial layers of the skin as well as in certain internal tissues. Most other deep tissues are sparsely supplied. Pain receptor are specific, but they are not as specific as others, because they can be activated by a variety of strong stimuli: 1) Mechanical stimuli; 2) Thermal stimuli; 3) Chemical pain stimuli.

Such as bradykinin, serotonin, histamine, potassium ions, acids, acetylcholine, proteolytic enzymes, Prostaglandins and substance P enhance the sensitivity of pain ending but do not directly excite themSection 1 somatic and visceral sensation-somatic sensation

Section 1 somatic and visceral sensation-visceral sensation Visceral sensation (visceral pain):The pain induced by visceral inflammation, sudden distention or mechanical stretch of viscera, ischemia, hyperkinesia is called visceral pain. When a disease affects a viscus, the disease process often spreads to the parietal peritoneum, pleura, or pericardium. The pain from parietal peritoneum, pleura, and pericardium is called parietal pain. For the parietal pain, the localization is accurate.

Section 1 somatic and visceral sensation-visceral sensation characteristics of visceral pain: 1. Poor localization 2. Slow-chronic type of pain 3. The pain receptors in the viscera are sensitive chemical damage, excess distention, stretching, not sensitive to cut, electrical stimulus. 4. Unpleasant emotional reaction and associated with nausea, vomiting and autonomic symptoms. 5. Referred pain and parietal pain

Section 1 somatic and visceral sensation-visceral sensationReferred pain: The pain felt in a part of one`s body that is considerably remote from the tissue causing the pain is called referred pain.

groin

Mechanism of Referred Pain

*Corpus callosum pons medulla cerebral cortex cerebral hemisphere gyrusspecific methods distinguishmore and short few and longProcess Integrate: analyze synthesize

Pyrimidal adj. in addition Sensory Neurons:Their peripheral ends terminate at receptors and central ends terminate at inter- or motor-neurons. These neurons serve to carry information from receptors into brain or spinal cord. Motor Neurons. They transmit the final integrated informations from the CNS out to the effector organs (muscles or glands). Interneurons: They lie within the CNS where they originate and terminate. Of all neurons 99% belong to this category. The number of interneurons in the pathway between the afferent and efferent neurons varies with the complexity of the action. Only one type of reflexes, the stretch reflex, possesses no interneuron, whereas complex reflexes may involve many interneurons. histaminergic transsection cross-section magnify neurilemma[,njuri'lem] :,Steady -70mv level. Inside of the cell negatively charged with respect to the outside is called polarization. These ions have a 10:10 fold difference in concentration between the inside and the outside of the cell.Sheath is an insulator() ,there is not sheath coating.:mode form The fashion of action potential propagation is local current flow .electronIntegrity: Impulse can conduct along the nerve only if the nerve is complete. Insulation: interfere with each other . non-fatigue :In one experiment, a sciatic nerve was stimulated at one end and action potential recorded at the other end and displayed on a computer. The stimulation, at the rate of 50 to 100 c/s, was maintained for several hours, and the action potentials as shown on the computer remained no significant decrease either in amplitude or in conduction velocity. Dorsal root anterior root Proprioception

Annulo-spiral:, correspond to

*Anterograde retrograde Cytoskeleton:, extend;extension;lasting;prolong; prolongation; to lengthen lyssa virus, mad dog bite limbs. tetanus() neurotrophin kinesin: dynein ATPase (adenosine triphosphatase)() Is correlated with

In the central nervous system,there are about 9 times more neuroglial cells than neurons.Ependymal cellsProcess: discriminate we can not discriminate these processesStable the extracellular K+ concentration: astrocytes can increase Na-K pump activity of itself,and make more K pump into the cells,and maintain normal electrocal activity.Lumen: pericyte layer zoom in Epilepsy , appear intensively()convulsion[kn'vln] ()of mouth and limbs The cause: ability of pump is weakened ,high concentration of K make depolarization of cells,excitability increase,form Epilepsy. symptom Debris: Microglia are capable of acting as phagocytes: regenerate*The most characteristic morphological feature of the electrical synapse is the closeapposition between the neuronal membranes. cardiac muscle has intercalated disc zoom in ,zoomed picture,figurezoom out district section ,part,portion zoom outConnexons connexin basic lipid bilayer the gap junctions represent low-resistance pathways for the direct conduction of electrical activity from one cell to another. Thereby they provide for a more rapid transmission of electrical signals between cells than at most chemical interspace Two connexons from adjacent cells form a docking()and are made up of a whole channel. The Diameter of the pore is 1.5-2nm.so only Ions and small molecules can pass through the channel.The gap junctions represent low-resistance pathways for the direct conduction of electrical activity from one cell to another. Thereby they provide for a more rapid transmission of electrical signals between cells than at most chemical synapses.so there is not synaptic delay. Synchronization: Because there is an intercalated disc between cardiac muscle cells,it is a gap junction ,so whole cardiac muscle almost contract as an entirety .and so it form a maximal contraction force . synchronize :varicosity. There are many small vesicles with a dense core in the varicosity. there are a lot of norepinephrine in these vesicles.NE can release from varicosity and diffuse to the receptors on the postsynaptic membrane.So it is not 1:1.

Angstroms mitochondria can provide energy for the cell.it is a place where energy form.CA:catecholamine neuropeptide small, clear synaptic vesicles means fluid in the vesicle is clear.gamma-aminobutyric acid:- catecholamines: neuropeptide:Postsynaptic memebrane is thickened,it is different from other parts of the cell.VDCC:voltage dependent calcium channel() concentration of calcium Each vesicle contains one quantum (several thousand molecules) of transmitter .The vesicles can fuse to the inner surface of the presynaptic terminal at specific release sites. The membrane then opens transiently so as to allow the vesicle to extrude its entire contents into the synaptic cleft by a process of exocytosis. This is in an all-or-none fashion. It might be that Ca2+ facilitates the transient fusion of the vesicular membrane with the presynaptic membrane, thereby enhancing the probability of the vesicle to release its contents. . be concerned with the number of Ca2+ influx affect the number of Neurotransmitter release.the type of NT determine Changes of MP of postsynaptic neuron.

the excitatory transmitters open up chemically gated channels. These chemically gated channels allow both Na+ and K+ to pass simultaneously. However, because of the large electrochemical gradient that tends to move sodium inward and because the potassium concentration gradient is not far from equilibrium with the electrical potential, this large opening of the membrane pores mainly allows sodium ions to rush to the inside of the membrane. The net effect()is the movement of ( + ) ions into the neuron, consequently, the postsynaptic cell is depolarized and thereby generates the EPSP. A single action potential usually leads only to an excitatory postsynaptic potential (EPSP) in the postsynaptic cells. This is an inadequate level of depolarization to fire the postsynaptic cell. However,The summation of EPSPs will reach its firing level and lead to an AP in postsynaptic cell.

Chlorine At the postsynaptic membrane of inhibitory synapses, the binding of the inhibitory transmitter to the receptors leads to a sudden increase in the membrane permeability to C1-or K+ ions.the inhibitory transmitter increases the postsynaptic cells permeability to both K+ and C1-. Consequently K+ ions move out of cell and C1- ions move into the cell. Both movements increase the membrane potential and hyperpolarize the postsynaptic membrane. The IPSP is thereby generated. :bind to effluxconductance, , graded in magnitude means the magnitude of local potential can increase with number of neurotransmitters.B. But the magnitude of an action potential do not reduce with the increase in distance.*But characteristic of propagation of AP: Integrity Insulation Propagation in two directions Relatively non-fatigue (less energy consumption, no transmitter exhaustion ). Only Axon terminal of presynaptic neuron release neurotranmitter .Receptors only exist on the membrane of postsynaptic neuron. *When an impulse reaches the presynaptic terminal, there is an interval of at least 0.5ms. This delay is due to the time it takes for the release of neurotransmitter and its action on the postsynaptic membrane. and then cause ions channel open()*The EPSP due to the activity in one synaptic knob by one action potential is too small to reach the firing level of postsynaptic neuron, but the EPSP produced by each of the active knobs may be summated. Summation may be spatial or temporal. When activity is present in more than one synaptic knob at the same time, spatial summation occurs and activity in one synaptic knob is said to facilitate the activity in another to approach the firing level.

generate ,evoke initiate

overlying build up summate fireTemporal summation occurs if repeated afferent stimuli cause new EPSPs before the preceeding( ones have decayed.When the frequency is low(50Hz). the preceeding local potential has decayed when the next stimulus is given.So they cannot summate.Frequency increase(200Hz) .Spatial and temporal facilitation are not an all or none response but is proportionate in size to the strength of the afferent stimulus. If the firing level of the cell is reached, a full-fledged() action potential is produced.Susceptibility asphyxia ischemiaWhen excitatory synapses are repetitively stimulated at a rapid rate, the number of discharges by the postsynaptic neuron is at first very great,but it becomes progressively less in succeeding milliseconds or seconds. This is called fatigue of synaptic transmission, which may be due to exhaustion of transmitters. *The importance of inhibitory processes for normal function of the CNS can be illustrated clearly by the following experiment. Strychnine() is a drug that blocks inhibitory synapses. If several milligrams of it is injected into an animal, severe convulsions set in within a few minutes, which finally lead to death. Inhibition is a fundamental process of central nervous activity and is just as important as excitation. The inhibitory effects may be either postsynaptic or presynaptic .*In this kind of inhibition, the excitability of the postsynaptic membrane is reduced due to generation of IPSP. The hyperpolarization caused by the IPSPs moves the membrane potential away from the firing level, thereby reduces or inhibits the effect caused by a simultaneous arrival of excitatory impulses. The inhibitory effect depends on the respective() magnitudes of the IPSPs and the EPSPs and their time course. There are two mainly types of it in the CNS. As mentioned previously, the afferents of muscle stretch receptors(spindles) form excitatory synapses at their homonymous motoneurons and inhibitory synapses with antagonistic() motoneurons. In the later case, the pathway is indirect because an inhibitory interneuron must be interposed to bring about a change from excitation to inhibition. This inhibition is called reciprocal inhibition() or antagonistic inhibition(). It is a widespread phenomenon in the CNS between antagonistic centers and very important for coordinating reflex activity. Flexor muscle extensor muscle Hammer knock; beat quadriceps muscle tendon leg extend (thigh)Neurons may also inhibit themselves in a negative feedback fashion (recurrent inhibion ). The motoneurons provide a particularly clear example of such a feedback inhibition. As shown in Fig. 12-7, the moto axons give off collaterals (to excite the inhibitory interneurons whose axons in turn form inhibitory synapses on the motoneurons. These inhibitory interneurons are called Renshaw cells. As the motoneurons become more excited, the Renshaw cells also become strongly excited, resulting in greater inhibition of the motoneurons. This slows or stops the discharges of the motor neurons. Similar inhibition via reccurrent collaterals is seen in the cerebral cortex and limbic system. In presynaptic inhibition, there is no change in the postsynaptic membrane, but a reduction in the release of transmitters at the presynaptic terminal of the excitatory synapse. Presynaptic inhibition is induced by an activation of axo-axonic synapses. As shown in Fig. 12-8, axon A forms a axon-somatic synapse with neuron C, while axon B forms an axo-axonal synapse with axon A. According to the arrangement of synaptic vesicles and the thick portions of the post-synaptic membrane, axon A is presynaptic to neuron C and axon B is presynaptic to axon A. Activation of the synaptic ending A (arrow in Fig 12-8A) induces an EPSP of approximately 10 mV in neuron C. The axo-somatic synapse is thus an excitatory synapse. If axon B is activated before axon A (arrows in Fig 12-8B), the amplitude of the EPSP is only 5 mV, although no IPSP occurs at the postsynaptic membrane of cell C. This form of EPSP inhibition without any change in the properties of the postsynaptic membrane is called presynaptic inhibition. It is not exactly clear what postsynaptic changes in permeability are triggered by activation of the axo-axonal synapse. But that activation of the axo-axonal synapse reduces the amount of transmitter substance released at the axo-somatic synapse is true. This is probably brought about by a reduction in the amplitude of the presynaptic action potential in ending A. Depolarization of axon A can in fact be observed during presynaptic inhibition. Since depolarization of the membrane potential leads to a reduced action potential amplitude, and since the release of transmitter substance is partly dependent on this amplitude, an action potential invading A during presynaptic inhibition will release less transmitter substance and thus induce a small EPSP.Presynaptic inhibition exists mainly at the excitatory synapses that are formed by the endings of afferent fibers in the spinal cord or thalamus. couplemutually, sideways spread*Serotonin5-affinity Tubocurarine -bungarotoxin:

recognizable beaded innervate dominatediffuseCriteria posses provided with the following item. pre-cursorsexternal application naturalReuptake:,, mimic Small molecule, rapidly acting transmitters: such as: Acetylcholine prolonged action such as :growth hormonetype of choline type of amines type of amino acids aspartate type of gas NO: Viagraexpand vessel penile erection CCK:Cholecystokinin Angiotensin origin from Angiotensinogen renin Negromodulate, ; decompose subunit make other channel activtedopenAcCoA:acetylcoenzyme A A choline CAT:choline acetyltransferase AChE:acetylcholinesterase acetate:The autonomic nervous system is made up of two neurons in series that connect the central nervous system and the effector cells.the first neuron has its cell body in the central nervour system.the synapse between the two neurons is outside the central nervous system in a cell cluster called an autonomic ganglion.the neuron passing between the central nervous system and the ganglion are called preganglionic neurons.the neurons passing between the ganglion and the effector are called postganglionic neurons.the two divisions also differ in the location of ganglion .the sympathtic ganglion lie close to spinal cord,In constract,the parasympathtic ganglion lie within or very close to the organs that postganglionic neurons innervate. *sympathetic chain sympathetic ganglion Form Synapselimbic systemNicotine,Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. MuscarineA toxic alkaloid found in Amanita muscaria (fly fungus). It is the first parasympathomimetic substance ever studied and causes profound parasympathetic activation that may end in convulsions and death. The specific antidote is atropine. *Arteriole bronchi bladder penis ejaculationMuscarine bronchus GI tract :gastrointestinal tract Adenylyl cyclase cAMPcyclic adenosine monophosphate=cyclic AMPEndoplasmic reticulum PLC:phospholipase c c IP3:inositol triphosphate DG:diacylglycerol PKC:protein kinase CPIP2:phosphatidylinosital biphosphate Tubocurarine Nicotine, hexamethonium decamethonium Sarin:An organophosphorous ester compound that produces potent and irreversible inhibition of cholinesterase,causing a buildup of Ach in the synaptic cleft. It is toxic to the nervous system and is a chemical warfare agent. organophosphate poisoningTyrosine dopa dopamine tyrosine hydroxylase aromatic amino acid decarboxylase dopamine hydroxylase catalysis catalyse*mesencephalonmidbrain Locus ceruleus of pons*Derivative adrenal medulla*3-R exist in fatty tissue and make fat decompose*: sphincter muscle of pupil arterioles :bronchi stomach motility( : pupil penis ejaculation uterus bladder digestive system urinary system*tuberomammillary nucleus Limbic system A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion).**nuclei of median raphe Serotonin5-HTR: 5-HT1~ 5-HT7 7*tuberomammillary nuclei .. its function is concerned with Arouse, sexual behavior, endocrine,BP, pain sensation, drink

*aspartate*In Pavlovs classical experiments, the salivation normally induced by placing meat in the mouth of a dog was studied. A bell was rung just before the meat was placed in the dogs mouth, and this was repeated a number of times until the animal would salivate when the bell was rung even though no meat was placed in its mouth. In this experiment, the meat placed in the mouth was unconditioned stimulus (US), because it normally produces secretion of saliva.The conditioned stimulus (CS) was the bell-ringing. After the CS and US had been paired a sufficient number of times, the CS produced the response originally, , evoked only by the US. An immense number of conditioned somatic, visceral, and other neural changes can be produced. indifferent stimulus Before the CR is formed,the CS is indifferent stimulus for secretion of saliva.because only the bell ringing cannot produce secretion of saliva. For example sucking reflex A person can suck the breast after birth.gradually unlimited( immense number changeable : maybe a song /call /and even a action paired with meat can produce secretion of saliva.*we can shrink our hand from the harmful stimulus quickly (draw back ones hand) nail puncture prick into not to scale arm***Divergence serves to make afferent information accessible to many neurons that are distributed in different parts of the CNS ,and thereby to expand the rang of action. Divergence connections allow activity at one site to influence many other sites. Several thousand axon collaterals converge to one motoneuron. Whether or not a motoneuron discharges a propagated action potential depends on the sum of the synaptic processes effective at any one time.promote reinforce inhibit collateralChain Circuit: Many interneurons are intercalated between afferent neuron and efferent neuron. Only interneurons can change the signal from facilitatory to inhibitory. Recurrent Circuit: In the excitatory recurrent circuit, the interneuron is excitatory and the activity produced by afferent signal may be greatly prolonged. In the inhibitory recurrent circuit, the interneuron is inhibitory and transmission will be shortened or stopped. dorsal column system Anterolateral system

Dorsal column system 1st order neurones medial lemnicusAnterolateral system

Visceral sensation coarse touchprincipalOlfactory bulb to be in charge of smell.MGB:medial geniculate body LGB:lateral geniculate body ventral posterolateral nucleus ventral posteromedial nucleus part; place; positionmammillary bodiesthe ventral lateral nucleus the pulvinar nucleiasynchronous fast waves synchronous slow waves

perception, , Example: a Canadian woman who was born with inability to sense pain died by age 28 from progressive damage to her joints, vertebrae, and effects of infection.

sharp pain pricking pain acute pain electric pain burning pain aching pain throbbing pain nauseous ,neospinothalamic tract paleospinothalamic tract seldomapprise; intolerable,, relieve,superficial layerbradykinin proteolytic enzymes prostaglandinsHyperkinesia , ischemia parietal peritoneum ,Distention , Nausea Vomiting parietal pain Irritation of a viscus frequently produces pain which is felt not in the viscus but in some somatic structures that may be a considerable distance away(Fig. 13-6). Such pain is said to be referred to the somatic structure. The best-known example is cardiac referred pain which is often refered to the inner side of the left arm. groin gallbladder diaphram

Convergence theory: There is a convergence of the visceral and somatic on the same spinothalamic neurons. Facilitation theory:The impulses from visceral structures reduce the threshold of spinothalamic neurons receiving afferents from somatic areas, so that minor activity in the pathway from the somatic areas excites the spinothalamic neurons, then passes into the brain.