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1、Cellular NeurobiologyNeuroscience Research InstitutePeking UniversityDepartment of NeurobiologyPeking University Health Science CenterAlbert Cheung-Hoi YU 于常海于常海北京大學神經科學研究所北京大學神經科學研究所One of the Cajals many drawings of Brain circuityThe letters label the different elements Cajal identified in an area

2、 of the human cerebral cortex that controls voluntary movement. Neurons: Excitable cells “wiring” “Signal Senders” Neuroglia: Support, Nurturing, InsulationCellular ComponentsNerve CellsNeuronsNeuroglia Cell body (soma; perikaryon) Axon : only one (branches are collaterals; terminals are end feet) D

3、endrites : much shorter; one or more than one; branch extensively into dendritic treesStructure of NeuronsAxon Hillock(Axonal end feet)The Axon and Axon Collaterals Cell Body (Soma): Life Support Protein Synthesis Single Nucleus, RER (Nissl Bodies) Axon: Longest process transmits messages away from

4、cell body Dendrites: Multiple processes off cell body receive messagesNeurons Structure & Function Neurons are similar to other cells in the body in some ways such as:1. Neurons are surrounded by a membrane. 2. Neurons have a nucleus that contains genes. 3. Neurons contain : What are inside of a

5、 neuron?Nucleus NucleolusMicrofilaments/NeurotubulesEndoplasmic Reticulum (ER) Mitochondria Golgi ApparatusNissl BodiesOthers Dendrites : dendrite tree Axon : axon hillock (axon origination) axonal transport system initial segment (first myelin sheath) action potential generation myelin sheath Axon

6、and DendritesAxonsDendritesTake information away from the cell bodyTake information to the cell bodySmooth surfaceRough surface (dendritic spines)Generally only 1 axon per cellUsually many dendrites per cellNo ribosomeHave ribosomesCan have myelinNo myelin insulationBranch further from the cell body

7、Branch near the cell bodyDifferences between Axons and DendritesNeuron Classification by ShapeMultipolar: “multi-” many processesMajority: Single axon, many dendrites (motor neuron and interneuron)Bipolar: “bi-” 2 processes Found in some sensory organs (retina, taste, smell, inner ear neuron) Unipol

8、ar (pseudo-unipolar): “uni -” 1 process (with branches)Sensory afferent neurons (dorsal root ganglia)Classification of Neurons by MorphologyClassification of Neurons by Axon Length1. Golgi type I NeuronsLong axons (longest from the cortex to the tip of spinal cord, 50-70 cm)2. Golgi type II NeuronsS

9、hort axons (shortest axons terminate only a few micron from cell body, interneurons)3. Amacrine NeuronsAn unusual cell type, lack axonsSensory neuron from receptor to CNS; receive stimuli and transmit afferent impulses to CNSInterneurons communicating between neurons; form circuits in the CNSMotor n

10、euron from CNS to effector cells; deliver efferent impulses out through the PNS to the effectors to carry out the actions directed by the CNSFunctional Classification of Neuron EXCITABLE Membrane: Able to regulate the movement of ions (charges) across and along membrane SIGNAL TRANSDUCTION DO NOT Re

11、plicate: Damaged cells cannot be replaced!Important Features of NeuronsAction PotentialFour Functional Regions of Model Neurons Impulse transmission : electrical chemical Morphology : axodendritic axonsomatic axoaxonic dendrodendriticClassification of Synapsessynapse4Vesicles release Neurotransmitte

12、rs Chemical synapse : presynaptic knob (presynaptic component) synaptic vesicles synaptic cleft postsynaptic membrane (postsynaptic component) Electrical synapse : gap junctionsSynapse Structures Types of synapseDis-tanceCytoplasmic continuityUltrastruct-ural componentAgent of trans-missionSynaptic

13、delayDirection of trans-missionElectrical3.5 nmYesGap-junction channelIon currentVirtually absentUsually bidirectionalChemical20-40 nmNoPresynaptic vesicle and active zone; postsynaptic receptorsChemical transmittersSignificant: at least 0.3 ms; usually 1-5 ms or longerUni-directional Distinguishing

14、 Properties of Electrical and Chemical SynapsesAt a chemical synapse, neurons transmit information across a cleft.1. Small Molecule Neurotransmitter SubstancesAcetylcholine (ACh); Dopamine (DA); Norepinephrine (NE); Serotonin (5-HT); Histamine2. Amino AcidsGamma-aminobutyric acid (GABA); Glycine; Gl

15、utamate; Aspartate3.Neuroactive Peptides - partial list!Bradykinin; beta-endorphin; calcitonin; cholecystokinin; enkephalin; dynorphin; insulin; gastrin; substance P; glucagon; secretin; vasopressin; oxytocin, etc. List of Some Neurotransmitters Axonal transport : intracellular communication Bidirec

16、tional mechanism : anterograde transport retrograde transport Classified by transport rates : slow transport system (0.2 to 1 mm/day) fast transport system (200 to 400 mm/day)Axonal Transport SystemsHitching a Ride on “Retrorail”Membranes of organelles involved in synaptic transmission are returned

17、to the cell body for reuse or degradationNucleusCytoskeleton(Anterograde transport)ComponentRate (mm/day)Structure and compositionFast transport Anterograde 200-400Small vesiculotubular structures, neurotransmitters; membrane proteins and lipidsMitochondria50-100MitochondriaRetrograde 200-300Lysosom

18、al vesicles and enzymesSlow transport SCb2-8Microfilaments, metabolic enzymes, clathrin complexSCa0.2-1Neurofilaments and microtubulesMajor Rate Components of Axonal Transport1. Neurons have specialized projections called dendrites and axons. Dendrites take information to the cell body and axons tak

19、e information away from the cell body2. Neurons communicate with each other through an electrochemical process3. Neurons contain some specialized structures (like synapses) and chemicals (like neurotransmitters)4. Nissl Bodies 5. DO NOT Replicate: Damaged cells cannot be replaced!Neurons differ from

20、 Other Cells Neuron : Supporting cells : CNS : neuroglia (glia) PNS : Schwann cells and satellite cells Functions : physical support electrical insulation metabolic exchange blood-brain barrierComposition of Nervous TissueTypes and Functions of GliaName of Glial CellFunctionAstrocyte (Astroglia)Star

21、-shaped cells that provide physical and nutritional support for neurons: 1) clean up braindebris; 2) transport nutrients to neurons; 3) hold neurons in place; 4) digest parts of dead neurons; 5) regulate content of extracellular space MicrogliaLike astrocytes, microglia digest parts of dead neurons.

22、Oligo-dendrogliaProvide the insulation (myelin) to neurons in the central nervous system.Satellite CellsPhysical support to neurons in the peripheral nervous system.Schwann CellsProvide the insulation (myelin) to neurons in the peripheral nervous system.Neuroglia in the CNSAble to replicate!Importan

23、ce in nervous system function is VASTLY underestimated!Evidence is mounting: 1. Nurturing role2. Signaling role (Memory?)3. Inflammation4. Pain5. Many more to come!Neuroglia: Distinguishing Features1. Presence of tight junctions between the endothelial cells2. One of the notable features of endothel

24、ial cells in comparison to other cell is the lack of pinocytic vesicles3. Selective permeability to molecules based on their molecular weight and lipid solubility4. Presence of specific markersRich in two enzymes: gamma glutamyl transpeptidase (GGTP) (for amino acid transport) and alkaline phosphata

25、se (transport of phsopahte ions) used as marker for BBB.Others: glucose transporter (GLUT-1); endothelial barrier antigen (EBA; unknown function) and antigen recognized by the MRC OX-47 monoclonal antibody (important for cell-to-cell adhesion); transferrin receptor (transport of ferric ions).Propert

26、ies of Blood Brain BarriersBBB1. Neurons have TWO processes called axons and dendrites. Glial cells only have ONE. 2. Neurons CAN generate action potentials. Glial cells CANNOT, however, do have a resting potential. 3. Neurons HAVE synapses that use neurotransmitters. Glial cells do NOT have chemica

27、l synapses. 4. Neurons do NOT continue to divide. Glial cells DO continue to divide. 5. There are many MORE (10-50 times more) glial cells in the brain compared to the number of neurons.Glia are different from neurons:Nerve CellsNeurons, Glia, Extracellular Space, and BloodBidirectional Communication Partners in the CNSReceiving signals from neighboring neurons and responding to them wi

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