Fundamentals of the Nervous System and Nervous Tissue

143
1 Fundamental s of the Nervous System and Nervous P A R T A Nervous Tissue

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Fundamentals of the Nervous System and Nervous Tissue

P A R T A

Nervous Tissue

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Nervous System

The master controlling and communicating system of the body

FunctionsSensory input –the stimuli goes to

CNS Integration – interpretation of

sensory inputMotor output – response to stimuli

coming from CNS

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Nervous System

Figure 11.1

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Organization of the Nervous System

Central nervous system (CNS) Brain and spinal cordIntegration and command center

Peripheral nervous system (PNS)Paired spinal and cranial nervesCarries messages to and from the

spinal cord and brain

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Peripheral Nervous System (PNS): Two Functional Divisions

Sensory (afferent) divisionSomatic sensory fibers – carry

impulses from skin, skeletal muscles, and joints to the brain

Visceral sensory fibers – transmit impulses from visceral organs to the brain

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Motor Division: Two Main Parts

Motor (efferent) division Somatic motor nervous

system (voluntary)- carries impulses from the CNS to skeletal muscles. Conscious control

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Motor Division: Two Main Parts

Visceral motor nervous system or Autonomic nervous system (ANS) (involuntary) - carry impulses from the CNS to smooth muscle, cardiac muscle, and glands Sympathetic and ParasympatheticEnteric Nervous System (ENS)

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Histology of Nerve Tissue

The two principal cell types of the nervous system are:Neurons – excitable cells that

transmit electrical signalsNeuroglias (glial) – cells that

surround and wrap neurons

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Supporting Cells: Neuroglia

NeurogliaProvide a supportive scaffolding

for neuronsSegregate and insulate neuronsGuide young neurons to the

proper connections Promote health and growth

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Neuroglia of the CNS

Astrocytes Most abundant, versatile, and highly

branched glial cells Maintain blood-brain barrier

They cling to neurons and their synaptic endings,

They wrap around capillariesRegulate their permeability

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Neuroglia of the CNS

Provide structural framework for the neuron

Guide migration of young neurons Control the chemical environment Repair damaged neural tissue

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Astrocytes

Figure 11.3a

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Neuroglia of the CNS

Microglia – small, ovoid cells with spiny processesPhagocytes that monitor the

health of neurons Ependymal cells – range in shape

from squamous to columnarThey line the central cavities of

the brain and spinal column

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Microglia and Ependymal Cells

Figure 11.3b, c

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Neuroglia of the CNS

Oligodendrocytes – branched cells Myelin

Wraps of oligodendrocytes processes around nerve fibers

Insulates the nerve fibers

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Neuroglia of the PNS

Schwann cells (neurolemmocytes) –Myelin

Wraps itself around nerve fibersInsulates the nerve fibers

Satellite cells surround neuron cell bodies located within the gangliaRegulate the environment around the

neurons

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Oligodendrocytes, Schwann Cells, and Satellite Cells

Figure 11.3d, e

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Neurons (Nerve Cells)

Structural units of the nervous systemComposed of a body, axon, and

dendritesLong-lived, amitotic, and have a

high metabolic rate Their plasma membrane function in:

Electrical signaling Cell-to-cell signaling during

development

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Neurons (Nerve Cells)

Figure 11.4b

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Nerve Cell Body (Perikaryon or Soma)

Contains the nucleus and a nucleolus

Is the major biosynthetic center Is the focal point for the outgrowth

of neuronal processes Has no centrioles (hence its amitotic

nature) Has well-developed Nissl bodies

(rough ER) Contains an axon hillock – cone-

shaped area from which axons arise

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Processes

Arm like extensions from the soma There are two types of processes:

axons and dendrites Myelinated axons are called tracts

in the CNS and nerves in the PNS

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Dendrites: Structure

Short, tapering processes They are the receptive, or input,

regions of the neuron Electrical signals are conveyed as

graded potentials (not action potentials)

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Neurons (Nerve Cells)

Figure 11.4b

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Axons: Structure

Slender processes of uniform diameter arising from the hillock

Long axons are called nerve fibers Usually there is only one

unbranched axon per neuron Axon collaterals Telodendria Axonal terminal or synaptic

knobs

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Axons: Function

Generate and transmit action potentials

Secrete neurotransmitters from the axonal terminals

Movement along axons occurs in two waysAnterograde — toward the axon

terminalRetrograde — toward the cell

body

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Myelin Sheath

Whitish, fatty (protein-lipoid), segmented sheath around most long axons

It functions to:Protect the axonElectrically insulate fibers from

one anotherIncrease the speed of nerve

impulse transmission

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Myelin Sheath and Neurilemma: Formation

Formed by Schwann cells in the PNS A Schwann cell:

Envelopes an axonEncloses the axon with its plasma

membraneHas concentric layers of

membrane that make up the myelin sheath

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Myelin Sheath and Neurilemma: Formation

Figure 11.5a–c

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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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Unmyelinated Axons

A Schwann cell surrounds nerve fibers but coiling does not take place

Schwann cells partially enclose 15 or more axons

Conduct nerve impulse slowly

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Axons of the CNS

Both myelinated and unmyelinated fibers are present

Myelin sheaths are formed by oligodendrocytes

Nodes of Ranvier are widely spaced

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Regions of the Brain and Spinal Cord

White matter – dense collections of myelinated fibers

Gray matter – mostly soma, dendrites, glial cells and unmyelinated fibers

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Neuron Classification

Structural: Multipolar — three or more

processesBipolar — two processes (axon

and dendrite)Unipolar — single, short process

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A Structural Classification of Neurons

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Neuron Classification

Functional: Sensory (afferent) — transmit

impulses toward the CNSMotor (efferent) — carry impulses

toward the body surfaceInterneurons (association

neurons) — any neurons between a sensory and a motor neuron

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Comparison of Structural Classes of Neurons

Table 11.1.1

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Comparison of Structural Classes of Neurons

Table 11.1.2

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Neurophysiology

Neurons are highly irritable Action potentials, or nerve impulses,

are:Electrical impulses carried along

the length of axonsAlways the same regardless of

stimulus

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Electricity Definitions

Voltage (V) – measure of potential energy generated by separated charge

Potential difference – voltage measured between two points

Current (I) – the flow of electrical charge between two points

Resistance (R) – hindrance to charge flow

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Electricity Definitions

Insulator – substance with high electrical resistance

Conductor – substance with low electrical resistance

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Electrical Current and the Body

Reflects the flow of ions rather than electrons

There is a potential on either side of membranes when:The number of ions is different

across the membraneThe membrane provides a

resistance to ion flow

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Role of Ion Channels

Types of plasma membrane ion channels:Nongated, or leakage channels –

always openChemically gated channels –

open with binding of a specific neurotransmitter

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Role of Ion Channels

Voltage-gated channels – open and close in response to membrane potential. 2 gates

Mechanically gated channels – open and close in response to physical deformation of receptors

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Gated Channels

Figure 12.13

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Operation of a Chemically Gated Channel

Example: Na+-K+ gated channel Closed when a neurotransmitter is

not bound to the extracellular receptorNa+ cannot enter the cell and K+

cannot exit the cell Open when a neurotransmitter is

attached to the receptorNa+ enters the cell and K+ exits

the cell

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Operation of a Voltage-Gated Channel

Example: Na+ channel Closed when the intracellular

environment is negative Na+ cannot enter the cell

Open when the intracellular environment is positive Na+ can enter the cell

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Gated Channels

When gated channels are open: Ions move quickly across the

membrane Movement is along their

electrochemical gradientsAn electrical current is createdVoltage changes across the

membrane

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Electrochemical 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

Electrochemical gradient – the electrical and chemical gradients taken together

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Resting Membrane Potential (Vr)

The potential difference (–70 mV) across the membrane of a resting neuron

It is generated by different concentrations of Na+, K+, Cl, and protein anions (A)

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Resting Membrane Potential (Vr)

Ionic differences are the consequence of:Differential permeability of the

neurilemma to Na+ and K+

Operation of the sodium-potassium pump

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Measuring Membrane Potential

Figure 11.7

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Resting Membrane Potential (Vr)

Figure 11.8

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Fundamentals of the Nervous System and Nervous Tissue

P A R T B

Nervous Tissue

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Membrane Potentials: Signals

Used to integrate, send, and receive information

Membrane potential changes are produced by:Changes in membrane

permeability to ionsAlterations of ion concentrations

across the membrane Types of signals – graded potentials

and action potentials

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Changes in Membrane Potential Changes are caused by three events

Depolarization – the inside of the membrane becomes less negative

Repolarization – the membrane returns to its resting membrane potential

Hyperpolarization – the inside of the membrane becomes more negative than the resting potential

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Depolarization, Repolarization and Hyperpolarization

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Graded Potentials

Short-lived, local changes in membrane potential

Decrease in intensity with distance Magnitude varies directly with the

strength of the stimulus Depolarization or hyperpolarization Sufficiently strong graded potentials

can initiate action potentials

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Graded Potentials

Figure 11.10

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Graded Potentials

Voltage changes are decremental Current is quickly dissipated due to

the leaky plasma membrane Only travel over short distances

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Action Potentials (APs)

A brief reversal of membrane potential with a total amplitude of 100 mV

Action potentials are only generated by muscle cells and neurons

They do not decrease in strength over distance

They are the principal means of neural communication

An action potential in the axon of a neuron is a nerve impulse

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Action Potential: Resting State

Na+ and K+ voltage gated channels are closed

Leakage accounts for small movements of Na+ and K+

Each Na+ channel has two voltage-regulated gates Activation gates Inactivation gates

Figure 11.12.1

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Action Potential: Resting State

Na channel is closed, but capable of opening

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Action Potential: Depolarization Phase

Na+ permeability increases; membrane potential reverses

Na+ gates are opened; K+ gates are closed

Threshold – a critical level of depolarization (-55 to -50 mV)

At threshold, depolarization becomes self-generating

Figure 11.12.2

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Action Potential: Depolarization Phase

Both Na channels are opened

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Action Potential: Repolarization Phase

Sodium inactivation gates close Membrane permeability to Na+

declines to resting levels As sodium gates close, voltage-

sensitive K+ gates open K+ exits the cell and internal

negativity of the resting neuron is restored

Figure 11.12.3

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Action Potential: Repolarization Phase

Na activation channel is opened and inactivation is closed.

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Action Potential: Hyperpolarization

Potassium gates remain open, causing an excessive efflux of K+

This efflux causes hyperpolarization of the membrane (undershoot)

Figure 11.12.4

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Action Potential: Hyperpolarization

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Action Potential: Role of the Sodium-Potassium Pump

Repolarization Restores the resting electrical

conditions of the neuronDoes not restore the resting ionic

conditions Ionic redistribution back to resting

conditions is restored by the sodium-potassium pump

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Phases of the Action Potential

• 1 – resting state• 2 – depolarization

phase• 3 – repolarization

phase• 4 –hyperpolarization

Figure 11.12

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Action Potential

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Propagation of an Action Potential along an Unmyelinated Axon

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Propagation of an action potential

Continuous propagationUnmyelinated axon

Saltatory propagationMyelinated axon

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Propagation of an Action Potential (Time = 0ms)- continuous propagation

Na gates open Na+ influx causes a patch of the axonal

membrane to depolarize Positive Na ions in the axoplasm move

toward the polarized (negative) portion of the membrane

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Propagation of an Action Potential (Time = 2ms)- continuous propagation

A local current is created that depolarizes the adjacent membrane in a forward direction

Local voltage-gated Na channels are opened

The action potential moves away from the stimulus

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Propagation of an Action Potential (Time = 4ms)- continuous propagation

Sodium gates close Potassium gates open Repolarization Hyperpolarization

Sluggish K channels are kept opened Resting membrane potential is restored

in this region

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Saltatory Conduction

Current 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 Conduction

Figure 11.16

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Types of stimuli

Threshold stimulusStimulus strong enough to bring

the membrane potential to a threshold voltage causing an action potential

Subthreshold stimulus weak stimuli that cause

depolarization (graded potentials) but not action potentials

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Coding for Stimulus Intensity

Action potential are All-or-none phenomenon

Strong stimuli can generate an action potential more often than weaker stimuli

The CNS determines stimulus intensity by the frequency of impulse transmission

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Stimulus Strength and AP Frequency

Figure 11.14

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Absolute Refractory Period

Time from the opening of the Na+ activation gates until the closing of inactivation gates

The absolute refractory period:Prevents the neuron from

generating an action potentialEnsures that each action potential

is separateEnforces one-way transmission of

nerve impulses

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Absolute and Relative Refractory Periods

Figure 11.15

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Relative Refractory Period

The interval following the absolute refractory period when:Sodium gates are closedPotassium gates are openRepolarization is occurring

Stimulus stronger than the original one cause a new action potential

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Conduction Velocities of Axons

Conduction velocities vary widely among neurons

Rate of impulse propagation is determined by:Axon diameter – the larger the

diameter, the faster the impulsePresence of a myelin sheath –

myelination dramatically increases impulse speed

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Nerve Fiber Classification

Nerve fibers are classified according to:DiameterDegree of myelinationSpeed of conduction

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Type A fibersDiameter of 4 to 20 µm and myelinated

Type B fibersDiameter of 2 to 4 µm and myelinated

Type C fibersDiameter less than 2 µm and

unmyelinated

Axon classification

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Multiple Sclerosis (MS)

An autoimmune disease that mainly affects young adults

Symptoms: visual disturbances, weakness, loss of muscular control, and urinary incontinence

Nerve fibers are severed and myelin sheaths in the CNS become nonfunctional scleroses

Shunting and short-circuiting of nerve impulses occurs

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Synapses

A junction that mediates information transfer from one neuron:To another neuronTo an effector cell

Presynaptic neuron – conducts impulses toward the synapse

Postsynaptic neuron – transmits impulses away from the synapse

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Synapses

Figure 11.17

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Types of Synapses

Axodendritic – synapses between the axon of one neuron and the dendrite of another

Axosomatic – synapses between the axon of one neuron and the soma of another

Others: Axoaxonic, etc

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Electrical Synapses

Electrical synapses:Are less common than chemical

synapsesCorrespond to gap junctions found in

other cell typesVery fast propagation of action

potentials

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Electrical Synapses

Are important in the CNS in:Arousal from sleepMental attentionEmotions and memoryIon and water homeostasisLight transmitting (eye)

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Chemical Synapses

Specialized for the release and reception of neurotransmitters

Typically composed of: Presynaptic neuron

Contains synaptic vesicles Postsynaptic neuron

The receptors are located typically on dendrites and soma

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Chemical Synapses

Synaptic CleftFluid-filled space separating the

presynaptic and postsynaptic neurons

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 Transfer

Nerve impulses reach the axonal terminal of the presynaptic neuron and open Ca2+ channels

Neurotransmitter is released into the synaptic cleft via exocytosis

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Synaptic Cleft: Information Transfer

Neurotransmitter crosses the synaptic cleft and binds to receptors on the postsynaptic neuron

Postsynaptic membrane permeability changes, causing an excitatory or inhibitory effect

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Synaptic vesiclescontaining neurotransmitter molecules

Axon of presynapticneuron

Synapticcleft

Ion channel(closed)

Ion channel (open)

Axon terminal of presynaptic neuron

PostsynapticmembraneMitochondrion

Ion channel closed

Ion channel open

Neurotransmitter

Receptor

Postsynapticmembrane

Degradedneurotransmitter

Na+Ca2+

1

2

34

5

Action

potential

Figure 11.18

Synaptic Cleft: Information Transfer

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Fundamentals of the Nervous System and Nervous Tissue

P A R T C

Nervous Tissue

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Termination of Neurotransmitter Effects

Neurotransmitter bound to a postsynaptic neuron: Produces a continuous postsynaptic

effectBlocks reception of additional

“messages” Must be removed from its receptor

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Termination of Neurotransmitter Effects

Removal of neurotransmitters occurs when they:Are degraded by enzymesAre reabsorbed by astrocytes or

the presynaptic terminals Diffuse from the synaptic cleft

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Synaptic Delay

Neurotransmitter must be released, diffuse across the synapse, and bind to receptors

Synaptic delay – time needed to do this

Synaptic delay is the rate-limiting step of neural transmission

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Postsynaptic Potentials

Neurotransmitter receptors mediate changes in membrane potential according to:The amount of neurotransmitter

releasedThe amount of time the

neurotransmitter is bound to receptors

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Postsynaptic Potentials

The two types of postsynaptic potentials are: EPSP – excitatory postsynaptic

potentials IPSP – inhibitory postsynaptic

potentials

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Excitatory Postsynaptic Potentials

EPSPs are graded potentials that can initiate an action potential in an axonUse only chemically gated

channelsNa+ and K+ flow in opposite

directions at the same time Postsynaptic membranes do not

generate action potentials

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Excitatory Postsynaptic Potential (EPSP)

Figure 11.19a

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Inhibitory Synapses and IPSPs

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

more permeable to potassium and chloride ions

Leaves the charge on the inner surface negative

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

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Inhibitory Postsynaptic (IPSP)

Figure 11.19b

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Summation

A single EPSP cannot induce an action potential

EPSPs must summate temporally or spatially to induce an action potential

Temporal summation – presynaptic neurons transmit impulses in rapid-fire order

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Temporal Summation

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Summation

Spatial summation – postsynaptic neuron is stimulated by a large number of terminals at the same time

IPSPs can also summate with EPSPs, canceling each other out

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Spatial Summation

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EPSP – IPSP Interactions

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Neurotransmitters

Chemicals used for neuronal communication with the body and the brain

50 different neurotransmitters have been identified

Classified chemically and functionally

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Chemical Neurotransmitters

Acetylcholine (ACh) Biogenic amines Amino acids Peptides Novel messengers: ATP and

dissolved gases NO and CO

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Neurotransmitters: Acetylcholine

First neurotransmitter identified, and best understood

Released at the neuromuscular junction

Synthesized and enclosed in synaptic vesicles

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Neurotransmitters: Acetylcholine

Degraded by the enzyme acetylcholinesterase (AChE)

Released by:All neurons that stimulate skeletal

muscleSome neurons in the autonomic

nervous system

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Neurotransmitters: Biogenic Amines

Include:Catecholamines – dopamine,

norepinephrine (NE), and epinephrine

Indolamines – serotonin and histamine

Broadly distributed in the brain Play roles in emotional behaviors

and our biological clock

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Synthesis of Catecholamines

Enzymes present in the cell determine length of biosynthetic pathway

Norepinephrine and dopamine are synthesized in axonal terminals

Epinephrine is released by the adrenal medulla

Figure 11.21

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Synthesis of Catecholamines

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Neurotransmitters: Amino Acids

Include:GABA – Gamma ()-aminobutyric

acid GlycineAspartateGlutamate

Found only in the CNS

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Neurotransmitters: Peptides Include:

Substance P – mediator of pain signals

Beta endorphin, dynorphin, and enkephalins

Act as natural opiates; reduce pain perception

Bind to the same receptors as opiates and morphine

Gut-brain peptides – somatostatin, and cholecystokinin

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Neurotransmitters: Novel Messengers

ATPIs found in both the CNS and PNSProduces excitatory or inhibitory

responses depending on receptor type

Induces Ca2+ wave propagation in astrocytes

Provokes pain sensation

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Neurotransmitters: Novel Messengers

Nitric oxide (NO) Activates the intracellular

receptor guanylyl cyclaseIs involved in learning and

memory Carbon monoxide (CO) is a main

regulator of cGMP in the brain

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Functional Classification of Neurotransmitters

Two classifications: excitatory and inhibitoryExcitatory neurotransmitters

cause depolarizations (e.g., glutamate)

Inhibitory neurotransmitters cause hyperpolarizations (e.g., GABA and glycine)

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Functional Classification of Neurotransmitters

Some neurotransmitters have both excitatory and inhibitory effects Determined by the receptor type

of the postsynaptic neuron Example: acetylcholine

Excitatory at neuromuscular junctions with skeletal muscle

Inhibitory in cardiac muscle

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Neurotransmitter Receptor Mechanisms

Direct: neurotransmitters that open ion channelsPromote rapid responses Examples: ACh and amino acids

Indirect: neurotransmitters that act through second messengersPromote long-lasting effectsExamples: biogenic amines,

peptides, and dissolved gases

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Channel-Linked Receptors

Composed of integral membrane protein

Mediate direct neurotransmitter action

Action is immediate, brief, simple, and highly localized

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Channel-Linked Receptors

Ligand binds the receptor, and ions enter the cells

Excitatory receptors depolarize membranes

Inhibitory receptors hyperpolarize membranes

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Channel-Linked Receptors

Figure 11.22a

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G Protein-Linked Receptors

Responses are indirect, slow, complex, prolonged, and often diffuse

These receptors are transmembrane protein complexes

First and Second messengers.

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(a)

(b)

Enzymeactivation

GTPGDP

Proteinsynthesis

Changes inmembranepermeabilityand potential

cAMP

PPi

ATP

Blocked ion flow

Channel closed Channel open

Ions flow

ReceptorG protein

Adenylatecyclase

Nucleus

Neurotransmitter (ligand)released from axon terminalof presynaptic neuron

Activation ofspecific genes

GTP

GTP

1

2

3

34

5

5

Figure 11.22b

Neurotransmitter Receptor Mechanism

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Neural Integration: Neuronal Pools

Functional groups of neurons that:Integrate incoming informationForward the processed

information to its appropriate destination

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Neural Integration: Neuronal Pools

Simple neuronal poolInput fiber – presynaptic fiberDischarge zone – neurons most

closely associated with the incoming fiber

Facilitated zone – neurons farther away from incoming fiber

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Simple Neuronal Pool

Figure 11.23

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Types of Neuronal Pools

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Types of Circuits in Neuronal Pools Divergent – information spreads

from one neuron to several neurons or from one pool to several pools.One motor neuron of the brain

stimulates many muscle fibers

Figure 11.24a, b

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Types of Circuits in Neuronal Pools

Convergent – input from many neurons is funneled to one neuron or neuronal poolsMotor neurons of the diaphragm is

controlled by different areas of the brain for subconscious and conscious functioning

Figure 11.24c, d

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Types of Circuits in Neuronal Pools

Reverberating –collateral branches of axons extend back toward the source of the impulse

Involved in rhythmic activitiesBreathing, sleep-wake cycle, etc

Figure 11.24e

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Types of Circuits in Neuronal Pools Parallel - incoming neurons

stimulate several neurons in parallel arrays

Divergence must take place before the parallel processingResponse to a painfull stimuli

causesWithdrawal of the limbShift of the weightFell painShout “ouch!”

Figure 11.24f

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Patterns of Neural Processing

Serial Transmitting of the impulse from

one neuron to another or from one pool to another

Spinal reflexes

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Development of Neurons

The nervous system originates from the neural tube and neural crest

The neural tube becomes the CNS There is a three-phase process of

differentiation:Proliferation of cells needed for

developmentMigration – neuroblasts become

amitotic and move externallyDifferentiation into neurons

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Axonal Growth Guided by:

Scaffold laid down by older neuronsOrienting glial fibersRelease of nerve growth factor by

astrocytesNeurotropins released by other

neuronsRepulsion guiding moleculesAttractants released by target cells