Chapter 10Chapter 10

Human Anatomy & Physiology I

Overview of the Nervous SystemOverview of the Nervous System

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

• Central Nervous System• brain• spinal cord

• Peripheral Nervous System• peripheral nerves

• cranial nerves• spinal nerves

Divisions of the Nervous SystemDivisions of the Nervous System

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:

Divisions Nervous SystemDivisions Nervous System

Levels of Organization in the Levels of Organization in the Nervous SystemNervous System

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

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

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

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

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

Levels of Organization in the Nervous SystemLevels of Organization in the Nervous System

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

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)

Generalized NeuronGeneralized Neuron

Neuron StructureNeuron Structure

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

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

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

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)

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

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

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

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

White Matter• contains myelinated axons

Gray Matter• contains unmyelinated structures• cell bodies, dendrites

Myelination of AxonsMyelination of Axons

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

Bipolar• two processes• eyes, ears, nose

Unipolar• one process• ganglia

Multipolar• many processes• most neurons of CNS

Classification of NeuronsClassification of Neurons

Classification of NeuronsClassification of Neurons

Multipolar — three or more processes

Bipolar — two processes (axon and dendrite)

Unipolar — single, short process

Structural

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

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

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

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.

Types of Neuroglial CellsTypes of Neuroglial Cells

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)

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

Ependymal CellsEpendymal CellsEpendymal cells – range in shape from squamous to columnar, many are ciliated

Line the central cavities of the brain and spinal column

OligodendrocytesOligodendrocytesOligodendrocytes – branched cells that line the thicker CNS nerve fibers and wrap around them, producing an insulating covering – the Myelin sheath

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

Regeneration of A Nerve AxonRegeneration of A Nerve Axon

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

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)

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

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

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

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

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

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)=

Resting Membrane PotentialResting Membrane PotentialA potential (-70mV) exists across the membrane of a resting neuron – the membrane is polarized

• inside is negative relative to the outside• polarized membrane• due to distribution of ions• Na+/K+ pump

Resting Membrane PotentialResting Membrane Potential

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

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)

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.

Changes in Membrane PotentialChanges in Membrane Potential

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

Graded PotentialsGraded Potentials

Voltage changes in graded potentials are decremental, the charge is quickly lost through the permeable plasma membrane

short- distance signal

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

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.

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?

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

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

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

• at rest membrane is polarized

• sodium channels open and membrane depolarizes

• potassium leaves cytoplasm and membrane repolarizes

• threshold stimulus reached

Potential ChangesPotential Changes

Phases of the Action PotentialPhases of the Action Potential

Impulse ConductionImpulse Conduction

Action PotentialsAction Potentials

Propagation of an Action Propagation of an Action PotentialPotential

The action potential is self-propagating and moves away from the stimulus (point of origin)

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

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

Stimulus Strength and AP Stimulus Strength and AP FrequencyFrequency

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

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)

Refractory Periods Refractory Periods

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)

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

Saltatory ConductionSaltatory Conduction

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

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)

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)

SynapsesSynapses

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

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

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

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

Synaptic Cleft: Information Synaptic Cleft: Information TransferTransfer

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

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

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

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

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”.

EPSPs and IPSPsEPSPs and IPSPs

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

SummationSummation

NeurotransmittersNeurotransmitters

Chemicals used for neuron communication with the body and the brain

More than 50 different neurotransmitters have been identified

Classified chemically and functionally

NeurotransmittersNeurotransmitters

Neurotransmitters – Chemical Neurotransmitters – Chemical classificationclassification

•Acetylcholine (ACh)

•Biogenic amines

•Amino acids

•Peptides

•Novel messengers: ATP and dissolved gases NO and CO

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

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

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

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

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

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

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.

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

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

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

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

G Protein-Linked Receptors: G Protein-Linked Receptors: MechanismMechanism

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

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

Simple Neuronal PoolSimple Neuronal Pool

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)

• 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

Types of Circuits in Neuronal Pools Types of Circuits in Neuronal Pools

Convergent – opposite of divergent circuits, resulting in either strong stimulation or inhibition

• 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

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)

Types of Circuits in Neuronal PoolsTypes of Circuits in Neuronal Pools •Parallel after-Discharge – incoming neurons stimulate several neurons in parallel arrays

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