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Transcript of Chapter 10
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Chapter 10Chapter 10
Human Anatomy & Physiology I
Overview of the Nervous SystemOverview of the Nervous System
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Organization of the Nervous SystemOrganization of the Nervous System
Peripheral nervous system - PNS
Paired Spinal and Cranial nerves
Carries messages to and from the spinal cord and brain – links parts of the body to the CNS
Central nervous system - CNS
Brain and Spinal Cord (in dorsal body cavity)
Integration and command center – interprets sensory input and responds to input
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• Central Nervous System• brain• spinal cord
• Peripheral Nervous System• peripheral nerves
• cranial nerves• spinal nerves
Divisions of the Nervous SystemDivisions of the Nervous System
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Nervous SystemNervous System
Sensory Input – monitoring stimuli occurring inside and outside the body
Integration – interpretation of sensory input
Motor Output – response to stimuli by activating effector organs
Functions:
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Divisions Nervous SystemDivisions Nervous System
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Levels of Organization in the Levels of Organization in the Nervous SystemNervous System
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Sensory Division• picks up sensory information and delivers it to the CNS
Motor Division• carries information to muscles and glands
Divisions of the Motor Division• Somatic – carries information to skeletal muscle• Autonomic – carries information to smooth muscle, cardiac muscle, and glands
Divisions of Peripheral Nervous SystemDivisions of Peripheral Nervous System
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Sensory Function• sensory receptors gather information• information is carried to the CNS
Integrative Function• sensory information used to create
• sensations• memory• thoughts• decisions
Motor Function• decisions are acted upon • impulses are carried to effectors
Functions of Nervous SystemFunctions of Nervous System
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PNS - Two Functional DivisionsPNS - Two Functional DivisionsSensory (afferent) Division
Somatic afferent nerves – carry impulses from skin, skeletal muscles, and joints to the CNS
Visceral afferent nerves – transmit impulses from visceral organs to the CNS
Motor (efferent) Division
Transmits impulses from the CNS to effector organs, muscles and glands, to effect (bring about) a motor response
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Sensory Neurons• afferent• carry impulse to CNS• most are unipolar• some are bipolar
Interneurons• link neurons• multipolar• in CNS
Motor Neurons• multipolar• carry impulses away from CNS• carry impulses to effectors
Classification of NeuronsClassification of Neurons
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Motor Division: two subdivisionsMotor Division: two subdivisionsSomatic Nervous System (voluntary)
Somatic motor nerve fibers (axons) that conduct impulses from CNS to Skeletal muscles – allows conscious control of skeletal muscles
Autonomic Nervous System (ANS) (involuntary)
Visceral motor nerve fibers that regulate smooth muscle, cardiac muscle, and glands
Two functional divisions – sympathetic and parasympathetic
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Levels of Organization in the Nervous SystemLevels of Organization in the Nervous System
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Histology of Nerve TissueHistology of Nerve TissueTwo principal cell types in the nervous system:
Neurons – excitable nerve cells that transmit electrical signals
Supporting cells – cells adjacent to neurons or cells that surround and wrap around neurons
Cell Types of Neural Tissue• neurons• neuroglial cells
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Neurons (Nerve Cells)Neurons (Nerve Cells)Highly specialized, structural units of the nervous system – conduct messages (nerve impulses) from one part of the body to another
Structure is variable, but all have a neuron cell body and one or more cell projections called processes.
Long life, mostly amitotic, with a high metabolic rate (cannot survive more than a few minutes without O2)
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Generalized NeuronGeneralized Neuron
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Neuron StructureNeuron Structure
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Nerve Cell Body (Perikaryon or Soma)Nerve Cell Body (Perikaryon or Soma)
Contains the nucleus and a nucleolus
The major biosynthetic center
Has no centrioles
Has well-developed Nissl bodies (rough ER)
Axon hillock – cone-shaped area where axons arise
Clusters of cell bodies are called Nuclei in the CNS and Ganglia in the PNS
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ProcessesProcesses
Extensions from the nerve cell body. The CNS contains both neuron cell bodies and their processes. The PNS consists mainly of neuron processes.
Two types: Axons and Dendrites
Bundles of neuron processes are called Tracts in the CNS and Nerves in the PNS
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Dendrites Dendrites Short, tapering, diffusely branched processes
The main receptive, or input regions of the neuron (provide a large surface area for receiving signals from other neurons)
Dendrites convey incoming messages toward the cell body
These electrical signals are not nerve impulses (not action potentials), but are short distance signals called graded potentials
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AxonsAxonsSlender processes with a uniform diameter arising from the axon hillock, only one axon per neuron
A long axon is called a nerve fiber, any branches are called axon collaterals
Terminal branches – distal ends are called the axon terminus (also synaptic knob or bouton)
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Axons: FunctionAxons: FunctionGenerate and transmit action potentials (nerve impulses), typically away from the cell body
As impulse reaches the axon terminals, it causes neurotransmitters to be released from the axon terminals
Movement of substances along axons:
Anterograde - toward axonal terminal (mitochondria, cytoskeletal, or membrane components)
Retrograde - away from axonal terminal (organelles for recycling)
Anterograde →
←Retrograde
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Myelin SheathMyelin Sheath
Whitish, fatty (protein-lipoid), segmented sheath around most long axons – dendrites are unmyelinated
•Protects the axon
•Electrically insulates fibers from one another
•Increases the speed of nerve impulse transmission
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Myelin Sheath Myelin Sheath Formed by Schwann cells in the PNS
A Schwann cell envelopes and encloses the axon with its plasma membrane.
The concentric layers of membrane wrapped around the axon are the myelin sheath
Neurilemma – cytoplasm and exposed membrane of a Schwann cell
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Nodes of Ranvier (Neurofibral Nodes)Nodes of Ranvier (Neurofibral Nodes)
Gaps in the myelin sheath between adjacent Schwann cells
They are the sites where axon collaterals can emerge
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White Matter• contains myelinated axons
Gray Matter• contains unmyelinated structures• cell bodies, dendrites
Myelination of AxonsMyelination of Axons
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Axons of the CNSAxons of the CNSBoth myelinated and unmyelinated fibers are present
Myelin sheaths are formed by oligodendrocytes
Nodes of Ranvier are more widely spaced
There is no neurilemma (cell extensions are coiled around axons)
White matter – dense collections of myelinated fibers
Gray matter – mostly soma and unmyelinated fibers
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Bipolar• two processes• eyes, ears, nose
Unipolar• one process• ganglia
Multipolar• many processes• most neurons of CNS
Classification of NeuronsClassification of Neurons
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Classification of NeuronsClassification of Neurons
Multipolar — three or more processes
Bipolar — two processes (axon and dendrite)
Unipolar — single, short process
Structural
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Neuron ClassificationNeuron ClassificationFunctional
Sensory (afferent) – transmit impulses toward the CNS
Motor (efferent) – carry impulses away from the CNS
Interneurons (association neurons) – lie between sensory and motor pathways and shuttle signals through CNS pathways
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Supporting Cells: NeurogliaSupporting Cells: Neuroglia
Six types of Supporting Cells - neuroglia or glial cells – 4 in CNS and 2 in the PNS
Each has a specific function, but generally they:
Provide a supportive scaffold for neurons
Segregate and insulate neurons
Produce chemicals that guide young neurons to the proper connections
Promote health and growth
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Schwann Cells• peripheral nervous system• myelinating cell
Oligodendrocytes• CNS• myelinating cell
Astrocytes• CNS• scar tissue• mop up excess ions, etc• induce synapse formation• connect neurons to blood vessels
Microglia• CNS• phagocytic cell
Ependyma• CNS• ciliated• line central canal of spinal cord• line ventricles of brain
Types of Neuroglial CellsTypes of Neuroglial Cells
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Supporting Cells: NeurogliaSupporting Cells: NeurogliaNeuroglia in the CNS
Astrocytes
Microglia
Ependymal Cells
Oligodendrocytes
Neuroglia in the PNS
Satellite Cells
Schwann Cells
Outnumber neurons in the CNS by 10 to 1, about ½ the brain’s mass.
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Types of Neuroglial CellsTypes of Neuroglial Cells
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AstrocytesAstrocytesMost abundant, versatile, highly branched glial cells
Cling to neurons, synaptic endings, and cover nearby capillaries
Support and brace neurons
Anchor neurons to nutrient supplies
Guide migration of young neurons
Aid in synapse formation
Control the chemical environment (recapture K+ ions and neurotransmitters)
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MicrogliaMicrogliaMicroglia – small, ovoid cells with long spiny processes that contact nearby neurons
When microorganisms or dead neurons are present, they can transform into phagocytic cells
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Ependymal CellsEpendymal CellsEpendymal cells – range in shape from squamous to columnar, many are ciliated
Line the central cavities of the brain and spinal column
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OligodendrocytesOligodendrocytesOligodendrocytes – branched cells that line the thicker CNS nerve fibers and wrap around them, producing an insulating covering – the Myelin sheath
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Schwann Cells and Satellite CellsSchwann Cells and Satellite Cells
Schwann cells - surround fibers of the PNS and form insulating myelin sheaths
Satellite cells - surround neuron cell bodies within ganglia
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Regeneration of A Nerve AxonRegeneration of A Nerve Axon
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NeurophysiologyNeurophysiology
Neurons are highly irritable (responsive to stimuli)
Action potentials, or nerve impulses, are:
Electrical impulses conducted along the length of axons
Always the same regardless of stimulus
The underlying functional feature of the nervous system
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DefinitionsDefinitionsVoltage (V) – measure of potential energy between two points generated by a charge separation
(Voltage = Potential Difference = Potential)
Current (I) – the flow of electrical charge
Resistance (R) – tendency to oppose the current
Insulator – substance with high electrical resistance
Conductor – substance with low electrical resistance
Units: V (volt), I (ampere), R (ohm)
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Ohm’s LawOhm’s Law
The relationship between voltage, current, and resistance is defined by Ohm’s Law
Current (I) = Voltage (V) Resistance (R)
In the body, electrical current is the flow of ions (rather than free electrons) across membranes
A Potential Difference exists when there is a difference in the numbers of + and – ions on either side of the membrane
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Membrane Ion ChannelsMembrane Ion Channels
Passive, or leakage, channels – always open
Chemically (or ligand)-gated channels – open with binding of a specific neurotransmitter (the ligand)
Voltage-gated channels – open and close in response to changes in the membrane potential
Mechanically-gated channels – open and close in response to physical deformation of receptors
Types of plasma membrane ion channels
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Ligand-Gated ChannelLigand-Gated ChannelExample: Na+-K+ gated channel
Closed when a neurotransmitter is not bound to the extracellular receptor
Open when a neurotransmitter is attached to the receptor - Na+ enters the cell and K+ exits the cell
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Voltage-Gated ChannelVoltage-Gated Channel•Example: Na+ channel
•Closed when the intracellular environment is negative
•Open when the intracellular environment is positive - Na+ can enter the cell
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Electrochemical GradientElectrochemical Gradient
Ions flow along their chemical gradient when they move from an area of high concentration to an area of low concentration
Ions flow along their electrical gradient when they move toward an area of opposite charge
Together, the electrical and chemical gradients constitute the ELECTROCHEMICAL GRADIENT
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Ion ChannelsIon ChannelsWhen gated ion channels open, ions diffuse across the membrane following their electrochemical gradients. This movement of charge is an electrical current and can create voltage change across the membrane.
Ion movement (flow) along electrochemical gradients underlies all the electrical phenomena in neurons.
Voltage (V) Current (I) x Resistance (R)=
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Resting Membrane PotentialResting Membrane PotentialA potential (-70mV) exists across the membrane of a resting neuron – the membrane is polarized
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• inside is negative relative to the outside• polarized membrane• due to distribution of ions• Na+/K+ pump
Resting Membrane PotentialResting Membrane Potential
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Resting Membrane PotentialResting Membrane Potential
Ionic differences are the consequence of:
•Different membrane permeabilities due to passive ion channels for Na+, K+, and Cl-
•Operation of the sodium-potassium pump
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Membrane Potentials: SignalsMembrane Potentials: Signals
Membrane potential changes are produced by:
•Changes in membrane permeability to ions
•Alterations of ion concentrations across the membrane
Neurons use changes in membrane potential to receive, integrate, and send information
Two types of signals are produced by a change in membrane potential:
•graded potentials (short-distance)
•action potentials (long-distance)
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Levels of PolarizationLevels of Polarization•Depolarization – inside of the membrane becomes less negative (or even reverses) – a reduction in potential
•Repolarization – the membrane returns to its resting membrane potential
•Hyperpolarization – inside of the membrane becomes more negative than the resting potential –an increase in potential
Depolarization increases the probability of producing nerve impulses. Hyperpolarization reduces the probability of producing nerve impulses.
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Changes in Membrane PotentialChanges in Membrane Potential
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Graded PotentialsGraded Potentials
Short-lived, local changes in membrane potential (either depolarizations or hyperpolarizations)
Cause currents that decreases in magnitude with distance
Their magnitude varies directly with the strength of the stimulus – the stronger the stimulus the more the voltage changes and the farther the current goes
Sufficiently strong graded potentials can initiate action potentials
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Graded PotentialsGraded Potentials
Voltage changes in graded potentials are decremental, the charge is quickly lost through the permeable plasma membrane
short- distance signal
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Action Potentials (APs)Action Potentials (APs)An action potential in the axon of a neuron is called a nerve impulse and is the way neurons communicate.
The AP is a brief reversal of membrane potential with a total amplitude of 100 mV (from -70mV to +30mV)
APs do not decrease in strength with distance
The depolarization phase is followed by a repolarization phase and often a short period of hyperpolarization
Events of AP generation and transmission are the same for skeletal muscle cells and neurons
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NaNa++ and K and K++ channels are closed channels are closedEach NaEach Na++ channel has two voltage-regulated channel has two voltage-regulated
gates gates Activation gates – Activation gates –
closed in the resting closed in the resting state state
Inactivation gates – Inactivation gates – open in the resting open in the resting statestate
Action Potential: Resting StateAction Potential: Resting State
Depolarization opens the activation gate (rapid) and closes the inactivation gate (slower) The gate for the K+ is slowly opened with depolarization.
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Depolarization PhaseDepolarization PhaseNa+ activation gates open quickly and Na+ enters causing local depolarization which opens more activation gates and cell interior becomes progressively less negative. Rapid depolarization and polarity reversal.
Threshold – a critical level of depolarization (-55 to -50 mV) where depolarization becomes self-generating
Positive Feedback?
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Repolarization PhaseRepolarization PhasePositive intracellular charge opposes further Na+ entry. Sodium inactivation gates of Na+ channels close.
As sodium gates close, the slow voltage-sensitive K+ gates open and K+ leaves the cell following its electrochemical gradient and the internal negativity of the neuron is restored
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HyperpolarizationHyperpolarization
The slow K+ gates remain open longer than is needed to restore the resting state. This excessive efflux causes hyperpolarization of the membrane
The neuron is insensitive to stimulus and depolarization during this time
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Role of the Sodium-Role of the Sodium-Potassium PumpPotassium Pump
Repolarization restores the resting electrical conditions of the neuron, but does not restore the resting ionic conditions
Ionic redistribution is accomplished by the sodium-potassium pump following repolarization
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• at rest membrane is polarized
• sodium channels open and membrane depolarizes
• potassium leaves cytoplasm and membrane repolarizes
• threshold stimulus reached
Potential ChangesPotential Changes
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Phases of the Action PotentialPhases of the Action Potential
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Impulse ConductionImpulse Conduction
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Action PotentialsAction Potentials
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Propagation of an Action Propagation of an Action PotentialPotential
The action potential is self-propagating and moves away from the stimulus (point of origin)
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Stimulus IntensityStimulus Intensity
How can CNS determine if a stimulus intense or weak?
Strong stimuli can generate an action potential more often than weaker stimuli and the CNS determines stimulus intensity by the frequency of impulse transmission
All action potentials are alike and are independent of stimulus intensity
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Threshold and Action PotentialsThreshold and Action Potentials
Threshold Voltage– membrane is depolarized by 15 to 20 mV
Subthreshold stimuli produce subthreshold depolarizations and are not translated into APs
Stronger threshold stimuli produce depolarizing currents that are translated into action potentials
All-or-None phenomenon – action potentials either happen completely, or not at all
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Stimulus Strength and AP Stimulus Strength and AP FrequencyFrequency
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Absolute Refractory PeriodAbsolute Refractory Period
The absolute refractory period is the time from the opening of the Na+ activation gates until the closing of inactivation gates
When a section of membrane is generating an AP and Na+ channels are open, the neuron cannot respond to another stimulus
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Relative Refractory PeriodRelative Refractory Period
The relative refractory period is the interval following the absolute refractory period when:
Na+ gates are closed
K+ gates are open
Repolarization is occurring
During this period, the threshold level is elevated, allowing only strong stimuli to generate an AP (a strong stimulus can cause more frequent AP generation)
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Refractory Periods Refractory Periods
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Axon Conduction VelocitiesAxon Conduction Velocities
Conduction velocities vary widely among neurons
Determined mainly by:
Axon Diameter – the larger the diameter, the faster the impulse (less resistance)
Presence of a Myelin Sheath – myelination increases impulse speed (Continuous vs. Saltatory Conduction)
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Saltatory ConductionSaltatory ConductionCurrent passes through a myelinated axon only at the nodes of Ranvier
Voltage-gated Na+ channels are concentrated at these nodes
Action potentials are triggered only at the nodes and jump from one node to the next
Much faster than conduction along unmyelinated axons
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Saltatory ConductionSaltatory Conduction
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Saltatory ConductionSaltatory ConductionCurrent passes through a myelinated axon only at the nodes of Ranvier (Na+ channels concentrated at nodes)
Action potentials occur only at the nodes and jump from node to node
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SynapseSynapse
A junction that mediates information transfer from one neuron to another neuron or to an effector cell
Presynaptic neuron – conducts impulses toward the synapse (sender)
Postsynaptic neuron – transmits impulses away from the synapse (receiver)
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Types of SynapsesTypes of SynapsesAxodendritic – synapse between the axon of one neuron and the dendrite of another
Axosomatic – synapse between the axon of one neuron and the soma of another
Other types:
Axoaxonic (axon to axon)
Dendrodendritic (dendrite to dendrite)
Dendrosomatic (dendrites to soma)
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SynapsesSynapses
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Electrical SynapsesElectrical SynapsesLess common than chemical synapses
Gap junctions allow neurons to be electrically coupled as ions can flow directly from neuron to neuron - provide a means to synchronize activity of neurons
Are important in the CNS in:
Arousal from sleep
Mental attention and conscious perception
Emotions and memory
Ion and water homeostasis
Abundant in embryonic nervous tissue
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Chemical SynapsesChemical SynapsesSpecialized for the release and reception of chemical neurotransmitters
Typically composed of two parts:
Axon terminal of the presynaptic neuron containing membrane-bound synaptic vesicles
Receptor region on the dendrite(s) or soma of the postsynaptic neuron
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Synaptic CleftSynaptic CleftFluid-filled space separating the presynaptic and postsynaptic neurons, prevents nerve impulses from directly passing from one neuron to the next
Transmission across the synaptic cleft:
Is a chemical event (as opposed to an electrical one)
Ensures unidirectional communication between neurons
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Synaptic Cleft: Information Synaptic Cleft: Information TransferTransfer
Nerve impulses reach the axon terminal of the presynaptic neuron and open Ca2+ channels
Neurotransmitter is released into the synaptic cleft via exocytosis
Neurotransmitter crosses the synaptic cleft and binds to receptors on the postsynaptic neuron
Postsynaptic membrane permeability changes due to opening of ion channels, causing an excitatory or inhibitory effect
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Synaptic Cleft: Information Synaptic Cleft: Information TransferTransfer
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Termination of Neurotransmitter EffectsTermination of Neurotransmitter Effects
Neurotransmitter bound to a postsynaptic neuron produces a continuous postsynaptic effect and also blocks reception of additional “messages”
Terminating Mechanisms:
Degradation by enzymes
Uptake by astrocytes or the presynaptic terminals
Diffusion away from the synaptic cleft
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Synaptic DelaySynaptic Delay
Neurotransmitter must be released, diffuse across the synapse, and bind to receptors (0.3-5.0 ms)
Synaptic delay is the rate-limiting step of neural transmission
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Postsynaptic PotentialsPostsynaptic PotentialsNeurotransmitter receptors mediate graded changes in membrane potential according to:
The amount of neurotransmitter released
The amount of time the neurotransmitter is bound to receptors
The two types of postsynaptic potentials are:
EPSP – excitatory postsynaptic potentials
IPSP – inhibitory postsynaptic potentials
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Excitatory Postsynaptic Excitatory Postsynaptic PotentialsPotentials
EPSPs are local graded depolarization events that can initiate an action potential in an axon
Na+ and K+ flow in opposite directions at the same time
Postsynaptic membranes do not generate action potentials. The currents created by EPSPs decline with distance, but can spread to the axon hillock and depolarize the axon to threshold leading to an action potential
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Inhibitory Postsynaptic Inhibitory Postsynaptic PotentialsPotentials
Neurotransmitter binding to a receptor at inhibitory synapses reduces a postsynaptic neuron’s ability to generate an action potential
Postsynaptic membrane is hyperpolarized due to increased permeability to K+ and/or Cl- ions. Na+ permeability is not affected.
Leaves the charge on the inner membrane face more negative and the neuron becomes less likely to “fire”.
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EPSPs and IPSPsEPSPs and IPSPs
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SummationSummation
IPSPs also summate and can summate with EPSPs.
Temporal Summation – presynaptic neurons transmit impulses in quick succession
Spatial Summation – postsynaptic neuron is stimulated by a large number of terminals at the same time
A single EPSP cannot induce an action potential EPSPs must summate (add together) to induce an AP
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SummationSummation
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NeurotransmittersNeurotransmitters
Chemicals used for neuron communication with the body and the brain
More than 50 different neurotransmitters have been identified
Classified chemically and functionally
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NeurotransmittersNeurotransmitters
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Neurotransmitters – Chemical Neurotransmitters – Chemical classificationclassification
•Acetylcholine (ACh)
•Biogenic amines
•Amino acids
•Peptides
•Novel messengers: ATP and dissolved gases NO and CO
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Released at the neuromuscular junctionReleased at the neuromuscular junction
Enclosed in synaptic vesiclesEnclosed in synaptic vesicles
Degraded by the acetylcholinesterase (AChE)Degraded by the acetylcholinesterase (AChE)
Released by:Released by:– All neurons that stimulate skeletal muscleAll neurons that stimulate skeletal muscle– Some neurons in the autonomic nervous Some neurons in the autonomic nervous
systemsystem
Neurotransmitters: Neurotransmitters: AcetylcholineAcetylcholine
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Include:Include:– Catecholamines – dopamine, Catecholamines – dopamine,
norepinephrine, and epinephrinenorepinephrine, and epinephrine– Indolamines – serotonin and histamineIndolamines – serotonin and histamine
Broadly distributed in the brainBroadly distributed in the brain
Play roles in emotional behaviors and our Play roles in emotional behaviors and our biological clockbiological clock
Neurotransmitters: Biogenic Neurotransmitters: Biogenic AminesAmines
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Synthesis of CatecholaminesSynthesis of Catecholamines
Enzymes present in the Enzymes present in the cell determine length cell determine length of biosynthetic of biosynthetic pathwaypathway
Norepinephrine and Norepinephrine and dopamine are dopamine are synthesized in axon synthesized in axon terminalsterminals
Epinephrine is released Epinephrine is released by the adrenal medullaby the adrenal medulla
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Include:Include:– GABA – Gamma (GABA – Gamma ()-aminobutyric )-aminobutyric
acid acid – GlycineGlycine– AspartateAspartate– GlutamateGlutamate
Found only in the CNSFound only in the CNS
Neurotransmitters: Amino AcidsNeurotransmitters: Amino Acids
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Include:Include:– Substance P – mediator of pain signalsSubstance P – mediator of pain signals– Beta endorphin, dynorphin, and Beta endorphin, dynorphin, and
enkephalinsenkephalins
Act as natural opiates, reducing our perception Act as natural opiates, reducing our perception of painof pain
Bind to the same receptors as opiates and Bind to the same receptors as opiates and morphinemorphine
Gut-brain peptides – somatostatin and Gut-brain peptides – somatostatin and cholecystokinin (produced by non-neural cholecystokinin (produced by non-neural tissue and widespread in GI tract)tissue and widespread in GI tract)
Neurotransmitters: PeptidesNeurotransmitters: Peptides
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ATPATP– Is found in both the CNS and PNSIs found in both the CNS and PNS– Produces excitatory or inhibitory responses Produces excitatory or inhibitory responses
depending on receptor typedepending on receptor type– Induces CaInduces Ca2+2+ wave propagation in astrocytes wave propagation in astrocytes– Provokes pain sensationProvokes pain sensation
Neurotransmitters: Novel Neurotransmitters: Novel MessengersMessengers
Nitric oxide (NO) – Activates the intracellular receptor guanylyl
cyclase– Is involved in learning and memory
Carbon monoxide (CO) is a main regulator of cGMP in the brain
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Two classifications: excitatory and inhibitoryTwo classifications: excitatory and inhibitory– Excitatory neurotransmitters cause Excitatory neurotransmitters cause
depolarizations depolarizations (e.g., glutamate)(e.g., glutamate)
– Inhibitory neurotransmitters cause Inhibitory neurotransmitters cause hyperpolarizations (e.g., GABA and glycine)hyperpolarizations (e.g., GABA and glycine)
Functional Classification of Functional Classification of NeurotransmittersNeurotransmitters
Some neurotransmitters have both excitatory and inhibitory effects (determined by the receptor type of the postsynaptic neuron). ACh is excitatory at neuromuscular junctions with skeletal muscle and Inhibitory in cardiac muscle.
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Direct: neurotransmitters that open ion Direct: neurotransmitters that open ion channelschannels– Promote rapid responses Promote rapid responses – Examples: ACh and amino acidsExamples: ACh and amino acids
Indirect: neurotransmitters that act Indirect: neurotransmitters that act through second messengersthrough second messengers– Promote long-lasting effectsPromote long-lasting effects– Examples: biogenic amines, peptides, and Examples: biogenic amines, peptides, and
dissolved gasesdissolved gases
Neurotransmitter Receptor Neurotransmitter Receptor MechanismsMechanisms
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Channel-Linked Receptors (ligand-Channel-Linked Receptors (ligand-gated ion channel)gated ion channel)
Mediate direct neurotransmitter action, action is immediate, brief, and highly localized
•Ligand binds to the receptor and ions enter the cells
•Excitatory receptors depolarize membranes
•Inhibitory receptors hyperpolarize membranes
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Responses are indirect, slow, complex, Responses are indirect, slow, complex, prolonged, and often diffuseprolonged, and often diffuse
These receptors are transmembrane These receptors are transmembrane protein complexes protein complexes
Examples: muscarinic ACh receptors, Examples: muscarinic ACh receptors, neuropeptides, and those that bind neuropeptides, and those that bind biogenic aminesbiogenic amines
G Protein-Linked ReceptorsG Protein-Linked Receptors
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Neurotransmitter binds to G protein-linked Neurotransmitter binds to G protein-linked receptorreceptor
G protein is activated and GTP is hydrolyzed to G protein is activated and GTP is hydrolyzed to GDPGDP
The activated G protein complex activates The activated G protein complex activates adenylate cyclase adenylate cyclase
Adenylate cyclase catalyzes the formation of Adenylate cyclase catalyzes the formation of cAMP from ATPcAMP from ATP
cAMP, a second messenger, brings about cAMP, a second messenger, brings about various cellular responsesvarious cellular responses
G Protein-Linked Receptors: G Protein-Linked Receptors: MechanismMechanism
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G Protein-Linked Receptors: G Protein-Linked Receptors: MechanismMechanism
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G protein-linked receptors activate intracellular G protein-linked receptors activate intracellular second messengers including Casecond messengers including Ca2+2+, cGMP, , cGMP, diacylglycerol, as well as cAMPdiacylglycerol, as well as cAMP
Second messengers:Second messengers:– Open or close ion channelsOpen or close ion channels– Activate kinase enzymesActivate kinase enzymes– Phosphorylate channel proteins Phosphorylate channel proteins – Activate genes and induce protein Activate genes and induce protein
synthesissynthesis
G Protein-Linked Receptors: G Protein-Linked Receptors: EffectsEffects
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Functional groups of neurons that:Functional groups of neurons that:Integrate incoming information received from Integrate incoming information received from
receptors or other neuronal poolsreceptors or other neuronal poolsForward the processed information to its Forward the processed information to its
appropriate destinationappropriate destination
Neural Integration: Neuronal PoolsNeural Integration: Neuronal Pools
Simple neuronal pool
Input fiber – presynaptic fiber
Discharge zone – neurons most closely associated with the incoming fiber
Facilitated zone – neurons farther away from incoming fiber
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Simple Neuronal PoolSimple Neuronal Pool
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Types of Circuits in Neuronal Pools Types of Circuits in Neuronal Pools
Divergent – one incoming fiber stimulates ever increasing number of fibers. These circuits are often amplifying circuits. (an impulse from a single brain neuron can activate 100 or more motor neurons in the spinal cord and → 1000s of skeletal muscle fibers)
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• one neuron sends impulses to several neurons• can amplify an impulse• impulse from a single neuron in CNS may be amplified to activate enough motor units needed for muscle contraction
DivergenceDivergence
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Types of Circuits in Neuronal Pools Types of Circuits in Neuronal Pools
Convergent – opposite of divergent circuits, resulting in either strong stimulation or inhibition
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• neuron receives input from several neurons• incoming impulses represent information from different types of sensory receptors• allows nervous system to collect, process, and respond to information• makes it possible for a neuron to sum impulses from different sources
ConvergenceConvergence
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Types of Circuits in Neuronal PoolsTypes of Circuits in Neuronal Pools
Reverberating or oscillating– chain of neurons containing collateral synapses with previous neurons in the chain. Involved in the control of rhythmic activities (sleep-wake cycle, breathing)
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Types of Circuits in Neuronal PoolsTypes of Circuits in Neuronal Pools •Parallel after-Discharge – incoming neurons stimulate several neurons in parallel arrays
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Multiple Sclerosis
Symptoms• blurred vision• numb legs or arms• can lead to paralysis
Causes• myelin destroyed in various parts of CNS• hard scars (scleroses) form• nerve impulses blocked• muscles do not receive innervation• may be related to a virus
Treatments• no cure• bone marrow transplant• interferon (anti-viral drug)• hormones
Clinical ApplicationClinical Application