CH 11- Functional Organization of Nervous Tissue Pt 2.

Gray matter

• contains neuron cell bodies, dendrites

Gray matter CNS

• Cortex- surface of the brain

• Nuclei- clusters deep within the brain

Gray matter PNS

• Ganglia- neuron cell bodies

White matter

bundles of myelinated axons

White matter CNS

• Nerve tracts- carry action potentials from one area of the CNS to another

White matter PNS

• Nerves- bundles of axons and their connective tissue coverings

Action Potential 

electrical signals produced by the nervous system

Membrane potential

measure of electrical properties of the plasma membrane due to

• ionic concentration differences across the plasma membrane

• permeability characteristics of the plasma membrane

Permeability of the plasma membrane

• determined by the ion channels and pumps

• sodium-potassium pump

  • help to maintain the difference in cytoplasmic and extracellular concentrations of ions

• leak channels

• gated channels

sodium-potassium pump

• help to maintain the difference in cytoplasmic and extracellular concentrations of ions

Leak channels

• always open

• responsible for permeability of the plasma membrane when it is at rest

• determine permeability of resting membrane

  • more permeable to K⁺ and Cl^- than to Na⁺

• specific for one type of ion

Gated Ion Channels 

• open and close due to a specific signal 

• ligand-gated ion channels

• voltage gated ion channels

• mechanically-gated ion channels

• thermoreceptors

Ligand-gated ion channels

• opened by binding of a specific molecule (ligand) on the extracellular side

• channel crosses the membrane

Voltage-gated ion channels

• open and close in response to specific voltage changes across the plasma membrane

• required for action potentials

Mechanically- gated ion channels

• open in response to mechanical stimulation

Thermoreceptors

• respond to temperature changes

Establishing resting membrane potential

• cytoplasm and extracellular fluid are electrically neutral

• charge difference across the plasma membrane 

is the plasma membrane polarized or unpolarized?

polarized

Potential difference

electrical charge difference across the plasma membrane

Resting membrane potential

potential difference in a resting cell

changes in resting membrane potential

• Ions diffuse down their concentration gradients 

• Movement results in electrical current and changes in resting membrane potential 

• Two types of changes:

  • Depolarization

  • Hyperpolarization

Depolarization

• inside the cell becomes more positive

• excitatory

• several factors leading to depolarization

Depolarization- excitatory state

always moves the membrnae potential closer to the point of action potential generation

Factors that can lead to depolarization of neurons

• Na⁺ entry

• Ca²⁺ entry

• Changes in extracellular K⁺ concentration

Sodium Ions

• Na⁺ entry is the most common cause of depolarization

• Limited Na⁺ leak channels

• Entry of Na⁺ is typically regulated

  • Ligand-gated Na⁺ or voltage-gated Na⁺ channels

Calcium Ions 

• Calcium enters the cell which causes depolarization

  • important for some cardiac muscle cells to generate action potentials

• Plays significant role in action potentials

  • regulates the voltage-gated sodium channels

  • regulation of neurotransmitter secretion at the presynaptic terminal

• Hypocalcemia- lower levels of Ca²⁺ in the blood

Hypocalcemia

• Lowers levels of Ca²⁺ in the blood

• Symptoms include nervousness and uncontrolled skeletal muscle contraction 

• Caused by lack of dietary Ca²⁺ or vitamin D or insufficient PTH

Potassium Ions

• Changes in extracellular K⁺ concentration can affect resting membrane potential 

• Increases can cause cytoplasmic K⁺ to stay inside the cell 

• When K⁺ stays inside the cell it can cause depolarization

Hyperpolarization

• Inside of the cell becomes even more negative

• Inhibitory-

  • makes the cell less likely to create an action potential  

Two major ways to hyperlarize neurons

• K⁺ exits 

• Cl^- enters

Potassium Ions

• Exit of K⁺ is primary cause of hyperpolarization after action potential 

• Voltage-gated K⁺ channels

• Ligand-gated K⁺ channels

  • mechanism for some inhibitory neurotransmitters 

• Hypokalemia

  • lower blood K⁺ concentration

Hypokalemia

• Lowers potassium concentration in the blood

• DECREASE in extracellular potassium can cause more potassium to exit the cell through leak channels

• Symptoms include muscular weakness, abnormal heart function, sluggish reflexes

• Cause by starvation, alkalosis, and some kidney diseases

Chloride ions

• Cl^- concentration is higher outside the cell

• Opening of ligand-gated Cl^- channels allows Cl^- to diffuse into the cell

• Some inhibitory neurotransmitters use this mechanism

Neuron Communication

1. Generation of action potentials

2. Action potential propagation along the axon

3. Communication with a target cell at the synapse

Graded Potentials

• Relatively small change in membrane potential localized to one area of the plasma membrane 

• vary in size depending on strength of the stimulus 

• Caused by several types of stimuli

  • chemicals binding to ligand-gated ion channels

  • changes in voltage triggering opening or closing of voltage-gated ion channels

  • mechanical stimuli opening mechanically gated ion channels

  • temperature changes affecting specific temperature receptors 

Graded potentials can be…..

• Hyperpolarizing- inhibitory

• Depolarizing-excitatory

Summation- Graded Potentials

• Combination/adding graded potentials 

• Large enough (reaches threshold) will result in an action potential

• Spread in decremental fashion

Action Potentials

• Used by neurons for communication

• Result from summation of graded potentials

• LARGE change in membrane potential

• Spreads (travels) without changing in magnitude over long distances

• Comes in phases 

Phases of an action potential

• Depolarization phase

• Repolarization phase

• Afterpotential 

• Return to resting membrane potential 

All-or-None Principle

• If graded potential reaches threshold, action potential is generated 

  • voltage-gated channels open altering membrane permeability

• If graded potential doe snot reach threshold, action potential is not generated 

  • membrane potential returns to resting potential  

Voltage-Gated Ion Channels & Action Potentials

• Required for generation of action potentials

• Comes in phases

Phases of an action potential in Voltage-Gated Ion Channels & Action Potentials

• Depolarization phase

• Repolarization phase

• After potential 

• Return to resting membrane potential 

Refractory Period

Plasma membrane becomes less sensitive to further stimulation

• Absolute refractory period

• Relative refractory period

Absolute refractory period

• First part of the refractory period

• Membrane is completely insensitive to stimulus

• From beginning of action potential until near the end of repolarization

• Lets depolarization and repolarization phases to be ompleted before another action potential can begin

• Prevents strong stimulus from causing prolonged depolarization of plasma membrane

Relative refractory period

• Stronger than threshold stimulus needed to start another action potential 

• Membrane is more permeable to K⁺

• Ends when voltage-gated K⁺ channels close and membrane potential returns to rest

Action Potential Frequency 

• Number of action potentials per unit of time in response to a stimulus

• Directly proportional to stimulus strength and to the size of the graded potential 

• Subthreshold stimulus 

• Threshold stimulus 

• Submaxial stimulus

• Maximal stimulus

• Supramaximal stimulus

Subthreshold stimulus

stimulus not strong enough to reach threshold, does not generate an action potential 

Threshold stimulus

graded potential just reaches threshold and causes a single action potential

Submaxial stimulus

stimuli between threshold and maximal stimulus strength

Maximal stimulus

strong enough to produce a maximum frequency of action potential

Supramaximal stimulus

stimulus stronger than maximal stimulus, does not increase action potential frequency

Propagation of Action Potentials

• Involves the generation of a new action potential in adjacent region of the plasma membrane

• Action potentials are generated in the trigger zone and travel in one direction down the axon 

Types of action potentials

• Continuous conduction

• Saltatory conduction

Continuous Conduction

• Happens in unmyelinated axons

• Generates an action potential in each section of the plasma membrane

• An action potential in one section of membrane allows for Na⁺ to diffuse to adjacent areas (local current) causing depolarization

• new identical action potential is generated in response to the depolarization

Saltatory conduction

• Happens in myelinated axons

• Action potential is conducted from one node of Ranvier to the next

Speed propagation depends on:

• Myelination

• Thickness of myelin sheath

• Diameter of the axon

Synapse is composed of

• Presyneptic cell

• Posynaptic cell

Types of Synapse

• Electrical synapses

• Chemical synapses

Electrical Synapses

• Happens between cells connected by gap junctions

• Allows ions flow from one cell to the next 

• Composed of connexons

  • 6 tubular proteins (connexin)

• Not common in nervous system

• Found in cardiac muscle and some smooth muscle

Chemical Synapses

• Chemical messenger (neurotransmitter) is used to communicate between the cells

• Release of neurotransmitter occurs due to action potential in the presynaptic terminal 

  • Voltage-gated Ca²⁺ channels open ad Ca²⁺ entering the axon terminal triggers exocytosis of the neurotransmitter 

Chemical synapses are composed of

• Presynaptic terminal-

  • axon terminal of the presynaptic cell that houses synaptic vesicles containing neurotransmitters

• Synaptic cleft-

  • space separating the cells

• Postsynaptic membrane-

  • membrane of the post synaptic cell (neuron, muscle cell, gland cell)

Neurotransmitter Removal

Neurotransmitter and receptor equilibrium:

• High concentration of neurotransmitter in synaptic cleft results in more receptor binding

• Rapid removal or destruction of neurotransmitter results in short term effects of neurotransmitter 

Receptors in Synapses

• Located on the postsynaptic cell

  • can also be found on some presynaptic cells

• Highly specific

• Determine the affect the neurotransmitter has on a cell

  • neurotransmitter can stimulate some cells and inhibit other

Neuron Communication

• Graded potential 

• Action potential 

  • depolarization

  • repolarization

• Action potential propagation

• Synaptic communication

Neurotransmitters

• Chemical messengers released from neurons

• Some neurons can secrete more than one type of neurotransmitter

Characteristics of neurotransmitters

• Must be synthesized by the neurons and stored in synaptic vesicles sin presynaptic terminal 

• Action potential must stimulate its exocytosis into synaptic cleft 

• Must bind to a specific receptor on. the post synaptic membrane

• Must evoke a response in the postsynaptic cell

Neurotransmitters are classified based on

• chemical structure

• effect on postsynaptic membrane

• mechanism of action at their target

Chemical classification of neurotransmitters

• Acetylcholine

• Biogenic amines

  • catecholamines

  • indoleamines

• Amino acids

• Purines

• Neuropeptides

• Gases and lipids

Acetylcholine

Synthesized from precursors acetic acid choline

Biogenic amines

• Catecholamines

  • derived from amino acid tyrosine, includes dopamine, norepinephrine, epinephrine

• Indoleamines

  • derived from histidine and tryptophan, includes histamine and serotonin

Amino acids

Includes GABA, glycines, glutamate

Purines

• Nitrogen containing compounds

• Includes adenosine and ATP

Neuropeptides

• 10-40 amino acids

• Includes substance P and endorphins

Gases and lipids

• Gases (gasotransmitters)- nitric oxide (NO) and carbon monoxide (CO)

• Lipids- endocannabinoids

Effect of Neurotransmitter on Postsynaptic Cells

• Excitatory

  • causes depolarization

  • makes cell more likely to generate an action potential 

  • Ex: glutamate, norepinephrine, dopamine

• Inhibitory

  • causes hyperpolarization

  • Makes cell less likely to generate an action potential 

  • Ex: GABA, serotonin, dopamine

Neurotransmitters mechanisms of action

• Ionotropic effect

• Metabotropic effect

Ionotropic effect

binding to ion channels

Metabotropic effect

binding to G protein-linked receptors

Postsynaptic Potentials

• Excitatory postsynaptic potential (EPSP)

• Inhibitory postsynaptic potential (IPSP)

Excitatory postsynaptic potential (EPSP)

• Depolarization

• Could generate an action potential 

• Typically results from increase permeability of membrane to Na⁺

Inhibitory postsynaptic potential (IPSP)

• Hyperpolarization

• Do not generate action potentials

• Typically results from increase in the plasma membranes premeability to Cl^- or K⁺

Neuromodulators

• Substance released by neurons that influence the likelihood of an action potential being generated in the postsynaptic cell

• Axoaxonic synapses-

  • axon of neuron synapses on the presynaptic terminal (axon) of another 

    • allows the release of neuromodulator to influence the action of another neuron

Neuromodulation

• Presynaptic inhibition

• Presynaptic facilitation

Presynaptic inhibition

• Amount of neurotransmitter released from presynaptic terminal is reduced

• Enkephalins and endorphins released by inhibitory axoaxonic synapses to reduce or eliminate pain sensation by blocking release of neurotransmitter from sensory neurons

Presynaptic facilitation

• Amount of neurotransmitter released from presynaptic terminal is elevated

• Serotonin released from axoaxonic synapses increases release of neurotransmitters

Summation of Graded Potential 

• Generation of an action potential is determined by the sum of all graded potentials generated by stimulation of the neuron

  • IPSP’s

  • EPSP’s

• Spatial summation

  • multiple action potentials get at the same time from separate neurons

• Temporal summation

  • two or more action potentials arrive very close together from the same neuron

Neural Pathways and Circuits

• Serial pathway

• Parallel pathway

Serial pathway 

• simples organization

• input travels along only one pathway

Parallel pathway

• most pathways

• more complex

• input travels along several pathwyas

• comes in different patterns

Patterns of parallel pathways

• Convergent pathways 

• Divergent pathways

• Reverberating circuits

• Parallel after-discharge circuits 

Convergent Pathways

• Multiple neurons converge upon and synapse with smaller number of neurons

• Allows different parts of the nervous system to activate or inhibit the activity of neurons

Divergent Pathways

• Smaller number of presynaptic neurons synapse with a larger number of postsynaptic neurons

• Allows information transmitted in one neuronal pathway to diverge into two or more pathways

Reverberating Circuits

• Chain of neurons with synapses with previous neurons in the chain 

• Makes positive-feedback loop

• Lets action potentials entering the circuit to cause a neuron farther along in the circuit to produce an action potential  more than once (after-discharge) to prolong response to stimulus

• Circuit will continue to discharge until the synapses are fatigued or inhibited by other neurons

• Control rhythmic activities

Parallel After-Discharge Circuits

• Neurons that stimulate neurons in parallel organization

• All converge upon a common output cell

• Involved in complex neuronal processes