Functions of the Nervous System Master Controlling and Communicating System of Body 1

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Nervous Tissue and Neuron Function

Fundamentals Of The Nervous System And Nervous Tissue

Learn and Understand

1. Like muscle cells, neurons use membrane polarity upset (AP) as a signal therefore keeping their membranes constantly ready (RMP). 2. Neuroglia help create and maintain the environmental conditions necessary for optimal neuron functioning. 3. In order to carry their message, some neurons have axons greater than 1 m in length. 4. Increasing the frequency of action potentials, not its strength, is how the NS controls the intensity of its message. 5. Graded potentials may sum to threshold depolarization causing AP in the neuron. The source of graded potentials is the up to 10,000 synapses with other neurons.

Functions of the Nervous System Master controlling and communicating system of body 1. Sensory: Receiving internal and external sensory input. 2. Integration: Process and evaluate, coordinate and control response 3. Motor: Generate response signals A. Controlling muscles and glands B. Maintaining homeostasis

Rapid and specific - usually causes almost immediate responses

Establishing and maintaining mental activity, consciousness, thinking, behavior, memory, emotion

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Figure 11.1 The nervous system’s functions.

Sensory input

Integration

Motor output

Anatomic Divisions of the Nervous System 100 Billion Neurons PNS: Consists mainly of nerves that extend from brain and spinal cord. 100 Million Neurons Cranial nerves to CNS: Integration and and from brain. control center. Spinal nerves to and Interprets sensory from spinal cord. input and dictates motor output Plexus – network of sensory input, motor output and integration outside of the CNS

Figure 11.2 Levels of organization in the nervous system.

Central nervous system (CNS) Peripheral nervous system (PNS) Brain and spinal cord Cranial nerves and spinal nerves Integrative and control centers Communication lines between the CNS and the rest of the body

Sensory (afferent) division Motor (efferent) division Somatic and visceral sensory Motor nerve fibers nerve fibers Conducts impulses from the CNS Conducts impulses from to effectors (muscles and glands) receptors to the CNS

Somatic nervous Autonomic nervous Somatic sensory fiber Skin system system (ANS) Somatic motor Visceral motor (voluntary) (involuntary) Conducts impulses Conducts impulses from the CNS to from the CNS to skeletal muscles cardiac muscles, smooth muscles, Visceral sensory fiber Stomach and glands Skeletal muscle

Motor fiber of somatic nervous system

Sympathetic division Parasympathetic Mobilizes body systems division during activity Conserves energy Promotes house- keeping functions during rest

Sympathetic motor fiber of ANS Heart

Structure Function Sensory (afferent) division of PNS Parasympathetic motor fiber of ANS Bladder Motor (efferent) division of PNS

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Histology of Nervous Tissue

• Highly cellular; little extracellular space • Two principal cell types – Neurons (nerve cells)—excitable cells that transmit electrical signals – Neuroglia – small cells that surround and wrap delicate neurons • CNS: – Astrocytes – Microglial cells – Ependymal cells – Oligodendrocytes • Satellite cells (PNS) • Schwann cells (PNS)

Neurons

• Structural units of nervous system • Large, highly specialized cells that conduct impulses • Extreme longevity (100 years or more) • Amitotic—with few exceptions • High metabolic rate—requires continuous supply of oxygen and glucose • All have cell body and one or more processes

Dendrites (receptive Soma = regions) Biosynthetic center of neuron Cell body (biosynthetic center Synthesizes proteins, membranes, and receptive region) and other chemicals Rough ER (chromatophilic substance or Nissl bodies) Most active and best developed in body Most neuron cell bodies in CNS Nuclei are clusters of neuron cell bodies in CNS Nucleus Dendrites Convey incoming messages toward cell body as graded potentials

Axon (impulse- Myelin sheath gap Impulse Nucleolus generating (node of Ranvier) direction Chromatophilic and -conducting substance (rough region) Axon endoplasmic terminals reticulum) Schwann cell (secretory region) Axon hillock Terminal branches

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Structure of a Motor Neuron

The Axon: Structure

• One axon per cell arising from axon hillock – Cone-shaped area of cell body • In some, axon short or absent, in others most of length of cell

• Long axons called nerve fibers • Occasional branches (axon collaterals) • Branches profusely at end (terminus) – Can be 10,000 terminal branches

• Distal endings called axon terminals or terminal boutons, axon bulbs, presynaptic terminals

The Axon: Functional Characteristics

• Generates and conducts AP

• Transmits AP along axolemma to axon terminal Neurotransmitters released into extracellular space

• Synapsed with many other neurons at same time

• Lacks rough ER and Golgi apparatus – Relies on cell body to renew proteins and membranes

• Quickly decay if cut or damaged

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Schwann cell plasma Segmented sheath membrane 1 around most long or Schwann cell cytoplasm large-diameter axons Axon Myelinated fibers Schwann cell nucleus Function of myelin Protects and electrically 2 insulates axon Increases speed of nerve impulse transmission

Nonmyelinated fibers conduct impulses more 3 slowly Myelin sheath Figure 11.5a Nerve fiber myelination by Schwann cells in the PNS. Schwann cell cytoplasm Myelination of a nerve fiber (axon)

Figure 11.5b Nerve fiber myelination by Schwann cells in the PNS.

Myelin sheath

Outer collar of perinuclear cytoplasm Axon (of Schwann cell)

Cross-sectional view of a myelinated axon (electron micrograph 24,000x)

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Functional Classifications: Sensory Transmit impulses from sensory receptors toward CNS Cell bodies in ganglia in PNS – ganglion is a grouping of NCBs outside of the CNS Motor Carry impulses from CNS to effectors Most cell bodies in CNS (except some autonomic neurons) Interneuron (association neuron) Lie between motor and sensory neurons Shuttle signals through CNS pathways; most are entirely within CNS 99% of body's neurons

Functional Classification of Neurons • Sensory – Transmit impulses from sensory receptors toward CNS – Almost all are Unipolar – Cell bodies in ganglia in PNS – ganglion is a grouping of NCBs outside of the CNS

• Motor – Carry impulses from CNS to effectors – Multipolar – Most cell bodies in CNS (except some autonomic neurons)

• Interneurons (association neurons) – Lie between motor and sensory neurons – Shuttle signals through CNS pathways; most are entirely within CNS – 99% of body's neurons

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The Resting Membrane Potential • Potential difference across membrane of resting cell – Approximately –70 mV in neurons • Actual voltage difference varies from -40 mV to -90 mV – Membrane termed polarized • Generated by: – Differences in ionic makeup of ICF and ECF • ECF has higher concentration of Na+ than ICF – Balanced chiefly by chloride ions (Cl-) • ICF has higher concentration of K+ than ECF – Balanced by negatively charged proteins • K+ plays most important role in membrane potential

– Differential permeability of the plasma membrane

Measuring Membrane Potential in Neurons

Figure 11.6 Operation of gated channels.

Open and close to change which ions move across membrane and when. One stimulated by messenger; one stimulated by electrical charge

Chemically gated ion channels Voltage-gated ion channels

Open in response to binding of the Open in response to changes appropriate neurotransmitter in membrane potential

Receptor Neurotransmitter chemical attached to receptor

Membrane Chemical voltage binds changes

Closed Open Closed Open

Each Na+ channel has two voltage-sensitive gates • Activation gates • Closed at rest; open with depolarization allowing Na+ to enter cell • Inactivation gates • Open at rest; block channel once it is open to prevent more Na+ from entering cell

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Differences in Plasma Membrane Permeability • Impermeable to large anionic proteins • Slightly permeable to Na+ (through leakage channels) – Sodium diffuses into cell down concentration gradient • 25 times more permeable to K+ than sodium (more leakage channels) – Potassium diffuses out of cell down concentration gradient • Quite permeable to Cl–

Membrane Potential Changes Used as Communication Signals

• Membrane potential changes when – Concentrations of ions across membrane change – Membrane permeability to ions changes • Changes produce two types signals – Graded potentials • Incoming signals operating over short distances • Mostly arrive at axodendritic and axosomatic synapses • Collectively control the post-synaptic neuron – Action potentials • Long-distance signals of axons

Action Potentials (AP)

• Principle way neurons send signals • Principal means of long-distance neural communication • Occur only in muscle cells and axons of neurons • Brief reversal of membrane potential with a change in voltage of ~100 mV • Do not decay over distance as graded potentials do

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Figure 11.11 The action potential (AP) is a brief change in membrane potential in a “patch” of membrane that is depolarized by local currents.

The big picture The key players Voltage-gated Na+ channels Voltage-gated K+ channels 1 Resting state 2 Depolarization Outside Outside cell cell

+30 3 3 Repolarization Inside Inside Activation Inactivation 0 cell gate gate cell 2 Action Closed Opened Inactivated Closed Opened potential 4 Hyperpolarization The events –55 Threshold Potassium Sodium channel Membrane potential (mV) potential Membrane –70 1 1 channel 4

0 1 2 3 4 Time (ms) Activation gates Inactivation The AP is caused by permeability changes in the gate plasma membrane: 1 Resting state

+30 3 Action potential 0 + 2 Na 4 Hyperpolarization 2 Depolarization permeability

K+ permeability permeability

–55 Relative membrane Relative

Membrane potential (mV) potential Membrane –70 1 1 4 0 1 2 3 4 Time (ms) 3 Repolarization

At threshold (–55 to –50 mV) positive feedback causes opening of all Na+ channels  a reversal of membrane polarity to +30mV

Figure 11.11 The action potential (AP) is a brief change in membrane potential in a “patch” of membrane that is depolarized by local currents. (1 of 3)

1 Resting state. No 2 Depolarization 3 Repolarization is ions move through is caused by Na+ caused by K+ flowing voltage-gated flowing into the cell. out of the cell. channels.

+30 3 0 4 Hyperpolarization is caused by K+ continuing to 2 Action potential leave the cell.

–55 Threshold

Membrane(mV) potential –70 1 1 4 0 1 2 3 4 Time (ms) Each K+ channel has one voltage-sensitive gate • Closed at rest; Opens slowly with depolarization Repolarization and hyperpolarization: • Slow voltage-gated K+ channels open • K+ exits the cell and internal negativity is restored

Role of the Sodium-Potassium Pump

• Repolarization resets electrical conditions, not ionic conditions • After repolarization Na+/K+ pumps (thousands of them in an axon) restore ionic conditions

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Figure 11.12a Propagation of an action potential (AP). Na+ influx causes local currents +30 Local currents cause Voltage depolarization of adjacent at 0 ms membrane areas in –70 direction away from AP origin (toward axon's

Membrane potential (mV) potential Membrane terminals) Recording electrode

Time = 0 ms. Action potential has not yet reached the recording electrode.

Resting potential

Peak of action potential

Hyperpolarization

Figure 11.12b Propagation of an action potential (AP).

Voltage at 2 ms +30

–70 Membrane potential (mV) potential Membrane

Since Na+ channels closer to AP origin are inactivated no new AP is generated there

Once initiated an AP is self- propagating Time = 2 ms. Action potential peak reaches the recording electrode.

Resting potential

Peak of action potential Hyperpolarization

Figure 11.12c Propagation of an action potential (AP).

+30

Voltage at 4 ms

–70 Membrane potential (mV) potential Membrane

Time = 4 ms. Action potential peak has passed the recording electrode. Membrane at the recording electrode is still hyperpolarized. Resting potential AP to propagates AWAY from the AP Peak of action potential origin Hyperpolarization

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Absolute and Relative Refractory Periods

• a period when a neuron is unable to respond to a new stimulus or is less responsive to stimulus • Absolute refractory period – Time from opening of Na+ channels until resetting of the channels – Ensures that each AP is an all-or-none event – Enforces one-way transmission of nerve impulses • Relative refractory period – Follows absolute refractory period • Most Na+ channels have returned to their resting state • Some K+ channels still open • Repolarization is occurring – Threshold for AP generation is elevated • Inside of membrane more negative than resting state

Figure 11.15 Action potential propagation in nonmyelinated and myelinated axons.

Stimulus Size of voltage

In bare plasma membranes, voltage decays. Without voltage-gated channels, as on a dendrite, ‘receptive zone’ graded potentials voltage decays because current leaks across the membrane.

Stimulus Voltage-gated ion channel

In nonmyelinated axons, conduction is slow (continuous conduction). Voltage-gated Na+ and K+ Group C fibers channels regenerate the action potential at each point along the axon, so voltage does not decay. Conduction is slow because it takes time for ions and for gates of channel proteins to move, and this must occur before voltage can be regenerated.

Stimulus Myelin Myelin sheath sheath gap Myelin 1 mm Group A & B sheath fibers

In myelinated axons, conduction is fast (saltatory conduction). Myelin keeps current in axons Saltatory conduction is about (voltage doesn’t decay much). APs are generated only in the myelin sheath gaps and appear to jump rapidly 30 times faster from gap to gap.

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Nerve Fiber Classification

• Group A fibers – Large diameter, myelinated somatic sensory and motor fibers of skin, skeletal muscles, joints – Transmit at 150 m/s • Group B fibers – Intermediate diameter, lightly myelinated fibers – Transmit at 15 m/s • Group C fibers – Smallest diameter, unmyelinated ANS fibers – Transmit at 1 m/s

Coding for Stimulus Intensity

• All action potentials are alike and are independent of stimulus intensity – How does CNS tell difference between a weak stimulus and a strong one? • Strong stimuli cause action potentials to occur more frequently – # Of impulses per second or frequency of APs • CNS determines stimulus intensity by the frequency of impulses – Higher frequency means stronger stimulus

Figure 11.13 Relationship between stimulus strength and action potential frequency.

Action potentials +30

–70 Membrane potential(mV) Membrane Stimulus Threshold

voltage Stimulus

Time (ms)

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Synapses

Synapse Classification • Axodendritic—between axon terminals of one neuron and dendrites of others • Axosomatic—between axon terminals of one neuron and soma of others • Less common types: – Axoaxonal (axon to axon) – Dendrodendritic (dendrite to dendrite) – Somatodendritic (dendrite to soma)

Important Terminology

• Presynaptic neuron – Neuron conducting impulses toward synapse – Sends the information • Postsynaptic neuron (in PNS may be a neuron, muscle cell, or gland cell) – Neuron transmitting electrical signal away from synapse – Receives the information • Most function as both

Figure 11.16 Synapses.

Axodendritic synapses

Dendrites Axosomatic synapses

Cell body Axoaxonal synapses

Axon

Axosomatic synapses

Cell body (soma) of postsynaptic neuron

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Varieties of Synapses: Electrical Synapses

• Less common than chemical synapses – Neurons electrically coupled (joined by gap junctions that connect cytoplasm of adjacent neurons) • Communication very rapid • May be unidirectional or bidirectional • Synchronize activity – More abundant in: • Embryonic nervous tissue • Cardiac muscle • Nerve impulse remains electrical

Varieties of Synapses: Chemical Synapses

• Specialized for release and reception of chemical neurotransmitters • Typically composed of two parts – Axon terminal of presynaptic neuron • Contains synaptic vesicles filled with neurotransmitter – Neurotransmitter receptor region on postsynaptic neuron's membrane • Usually on dendrite or cell body • Two parts separated by synaptic cleft – Fluid-filled space • Electrical impulse changed to chemical across synapse, then back into electrical

Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Enzymatic degradation Presynaptic Reuptake neuron

Presynaptic Diffusion away neuron from synapse Postsynaptic neuron

1 Action potential arrives at axon terminal.

2 2+ Voltage-gated Ca Mitochondrion channels open and Ca2+ enters the axon terminal.

3 Ca2+ entry Synaptic causes synaptic cleft vesicles to release Axon terminal neurotransmitter Synaptic by exocytosis vesicles

4 Neurotransmitter diffuses across the synaptic cleft and Postsynaptic binds to specific receptors on neuron the postsynaptic membrane.

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Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.

Ion movement Graded potential

5 Binding of neurotransmitter opens ion channels, resulting in graded potentials.

Synaptic Delay

• Time needed for neurotransmitter to be released, diffuse across synapse, and bind to receptors – 0.3–5.0 ms • Synaptic delay is rate-limiting step of neural transmission

Neurotransmitters

• Language of nervous system • 50 or more neurotransmitters have been identified • Most neurons make two or more neurotransmitters – Neurons can exert several influences • Usually released at different stimulation frequencies • Classified by chemical structure and by function

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Classification of Neurotransmitters: Function • Effects - excitatory versus inhibitory – Neurotransmitter effects can be excitatory (depolarizing) and/or inhibitory (hyperpolarizing) – Effect determined by receptor to which it binds • Acetylcholine and NE bind to at least two receptor types with opposite effects – ACh excitatory at neuromuscular junctions in skeletal muscle – ACh inhibitory in cardiac muscle

Figure 11.20 Direct neurotransmitter receptor mechanism: Channel-linked receptors.

Ion flow blocked Ions flow Ligand

Closed ion Open ion channel channel

Direct action Neurotransmitter binds to and opens ion channels

Promotes rapid responses by altering membrane potential

Examples: ACh and amino acids

Graded Potentials

• Short-lived, localized changes in membrane potential – Magnitude varies with stimulus strength – Stronger stimulus  more voltage changes; farther current flows • Either depolarization or hyperpolarization • Triggered by stimulus that opens gated ion channels • Current flows but dissipates quickly and decays – Graded potentials are signals only over short distances

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Figure 11.9a Depolarization and hyperpolarization of the membrane.

Depolarizing stimulus

+50

Inside positive 0 Inside negative

–50 Depolarization

–70 Resting Decrease in membrane potential potential (toward zero and above) MembranemV) (voltage, potential –100 Inside of membrane becomes less 0 1 2 3 4 5 6 7 Time (ms) negative than resting membrane potential Depolarization: The membrane potential moves toward 0 mV, the inside becoming less negative (more positive). Increases probability of producing a nerve impulse

Figure 11.9b Depolarization and hyperpolarization of the membrane.

Hyperpolarizing stimulus

+50

–50 Resting potential –70 Hyper- An increase in membrane polarization –100 potential (away from zero) MembranemV) (voltage, potential 0 1 2 3 4 5 6 7 Time (ms) Inside of cell more negative than Hyperpolarization: The membrane potential resting membrane potential) increases, the inside becoming more negative.

Reduces probability of producing a nerve impulse

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Excitatory Synapses and EPSPs

• Neurotransmitter binding opens chemically gated channels • Allows simultaneous flow of Na+ and K+ in opposite directions • Na+ influx greater than K+ efflux  net depolarization called EPSP (not AP) • EPSP help trigger AP if EPSP is of threshold strength – Can spread to axon hillock, trigger opening of voltage-gated channels, and cause AP to be generated

Figure 11.18a Postsynaptic potentials can be excitatory or inhibitory.

+30 An EPSP is a local depolarization of the 0 postsynaptic membrane that brings the neuron closer to AP threshold. Neurotransmitter binding opens chemically gated Threshold ion channels, allowing –55 Na+ and K+ to pass –70 through simultaneously.

Membrane potential(mV) Membrane Stimulus

10 20 30 Time (ms) Excitatory postsynaptic potential (EPSP)

Inhibitory Synapses and IPSPs

• Reduces postsynaptic neuron's ability to produce an action potential – Makes membrane more permeable to K+ or Cl– • If K+ channels open, it moves out of cell • If Cl- channels open, it moves into cell – Therefore neurotransmitter hyperpolarizes cell • Inner surface of membrane becomes more negative • AP less likely to be generated

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Figure 11.18b Postsynaptic potentials can be excitatory or inhibitory.

+30 An IPSP is a local hyperpolarization of the postsynaptic membrane 0 that drives the neuron away from AP threshold. Neurotransmitter binding opens K+ or Cl– channels. Threshold –55 –70

Membrane potential(mV) Membrane Stimulus

10 20 30 Time (ms) Inhibitory postsynaptic potential (IPSP)

Synaptic Integration: Summation

• A single EPSP cannot induce an AP • EPSPs can summate to influence postsynaptic neuron • IPSPs can also summate • Temporal summation • Spatial summation • Most neurons receive both excitatory and inhibitory inputs from thousands of other neurons – Only if EPSP's predominate and bring to threshold  AP

Postsynaptic Potentials and Their Summation

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Temporal Summation

Spatial Summation

Integration of EPSPs and IPSPs

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Integration: Presynaptic Inhibition

• Excitatory neurotransmitter release by one neuron inhibited by another neuron via an axoaxonal synapse • Less neurotransmitter released • Smaller EPSPs formed

Additional Slides

• May not be shown on screen in class

Capillary

Neuron

Astrocyte

Astrocytes are the most abundant CNS neuroglia.

1. Support and brace neurons 2. Play role in exchanges between capillaries and neurons 3. Guide migration of young neurons 4. Control chemical environment around neurons

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Neuron Microglial cell

Microglial cells are defensive cells in the CNS.

1. Migrate toward injured neurons 2. Can transform to phagocytize microorganisms and neuronal debris

Fluid-filled cavity Cilia

Ependymal cells

Brain or spinal cord tissue Ependymal cells line cerebrospinal fluid–filled cavities.

1. Range in shape from squamous to columnar 2. May be ciliated - Cilia beat to circulate CSF 3. Line the central cavities of the brain and spinal column 4. Form permeable barrier between CSF in cavities and tissue fluid bathing CNS cells

Myelin sheath

Process of oligodendrocyte

Nerve fibers

Oligodendrocytes have processes that form myelin sheaths around CNS nerve fibers.

1. Branched cells 2. Processes wrap CNS nerve fibers, forming insulating myelin sheaths thicker nerve fibers

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Satellite cells Cell body of neuron Schwann cells (forming myelin sheath) Nerve fiber

Satellite cells and Schwann cells (which form myelin) surround neurons in the PNS.

Satellite cells Surround neuron cell bodies in PNS Function similar to astrocytes of CNS Schwann cells (neurolemmocytes) Surround all peripheral nerve fibers and form myelin sheaths in thicker nerve fibers Similar function as oligodendrocytes Vital to regeneration of damaged peripheral nerve fibers