Chapter 7

Neurilemma

All axons in the PNS are surrounded by a sheath of Schwann cells called the Neurilemma or Sheath of Schwann

Axonal transport

An active process needed to move organelles and proteins from the cell body to axon terminals -Some viruses and bacteria use retrograde transport to reach the cell body. Researchers are investigating to use this type of transport to correct defective genes.

Tract

Grouping of axons that interconnect regions of the CNS

Ganglion

Grouping of neuron cell bodies located outside CNS

Nucleus

Grouping of neuron cell bodies within the CNS

Peripheral nervous system

cranial and spinal nerves - nerves, ganglia, and nerve plexus * outside of the CNS

Conduction in an unmyelinated neuron

•Axon potentials are produced down the entire length of the axon. •The conduction rate is slow because so many action potentials are generated.

Nicotinic ACh receptors

•Can be stimulated by nicotine •Found on the motor end plate of skeletal muscle cells, in autonomic ganglia, and in some parts of the CNS

*Bipolar neurons

have two processes, one on either end; found in retina of eye

Medication effects

-Local anesthetics Na-channel blockers -Cocaine first local anesth. - toxic & abuse -Procaine Novocaine -Lidocaine Xylocaine - Tetrodotoxin Na-Channel blocker: A potent toxin in the ovary of the puffer fish - fugu's puffer dish in Japan ovaries have to be removed completely by the chefs.

oligodendrocyte

- 1 oligodendrocyte sends extensions to several axons and each wraps around a section of an axon -Produces the myelin sheath but NOT a neurilemma

Classification of Nerves

-Nerves are bundles of axons located outside the CNS -A bundle of axons in the CNS is called a tract. -Most are composed of both sensory and motor neurons and are called mixed nerves

Axon

- Conducts action potentials from axon hillock where action potentials are generated away from the cell body Dendrites and axons are processes or extensions from the cell body.

Cell body

-A cell body that contains the nucleus and other organelles

Coding for Stimulus Intensity

-A stronger stimulus will make action potentials occur more frequently. frequency modulated. -A stronger stimulus may also activate more neurons in a nerve. This is called recruitment.

Acetylcholinesterase AChE

-AChE is an enzyme that inactivates ACh activity shortly after it binds to the receptor. -Hydrolyzes ACh into acetate and choline, which are taken back into the presynaptic cell for reuse.

Changes in Membrane Potential - Action Potentials

-At rest, a neuron is considered polarized when the inside is more negative than the outside. -When the membrane potential inside the cell increases (becomes more positive), this is called depolarization. -A return to resting potential is called repolarization. -When the membrane potential inside the cell decreases (becomes more negative), this is called hyperpolarization.

Process of PNS Regeneration

-CNS axons are not as able to regenerate. -Death receptors form that promote apoptosis of oligodendrocytes. -Inhibitory proteins called Nogo in the myelin sheath prevents regeneration. -Glial scars from astrocytes form that also prevent regeneration. -Any injury in the CNS is final.

*BBB

-Capillaries in the brain do not have pores between adjacent cells but are joined by tight junctions. -Substances can only be moved by very selective processes of diffusion through endothelial cells, active transport, and bulk transport -Can also create problems with chemotherapy of brain diseases because many drugs can not penetrate the BBB.

Ion Channels in Axons

-Changes in membrane potential: Controlled by changes in the ion flow through channels. -K+ has two types of channels: -Not gated (always open); sometimes called K+ leakage channels - Voltage-gated K+ channels; open when a particular membrane potential is reached; closed at resting potential -Na+ has only voltage-gated channels that are closed at rest; the membrane is less permeable to Na+ at rest.

Action potential

-Depolarization of the cell is excitatory. -Hyperpolarization is inhibitory

Monoamine Action and Inactivation

-Like ACh, monoamines are made in the presynaptic axon, released via exocytosis, diffuse across the synapse, and bind to specific receptors. -They are quickly taken back into the presynaptic cell (called reuptake) and degraded by monoamine oxidase (MAO).

EPSPs and IPSPs

-EPSPs move the membrane potential closer to threshold; may require EPSPs from several neurons to actually produce an action potential -IPSPs move the membrane potential farther from threshold. -Can counter EPSPs from other neurons so summation of EPSPs and IPSPs at the initial segment of the axon next to the axon hillock determines whether an action potential occurs.

Synapses - Introduction

-Functional connection between a neuron and the cell it is signaling. -In the CNS, this second cell will be another neuron. -In the PNS, the second cell will be in a muscle or gland; often called neuromuscular junctions

G-Protein Coupled Channels

-G-proteins have three subunits alpha, beta, and gamma. Binding of one ACH results in the dissociation of the alpha subunit. -Binding of acetylcholine opens K+ channels in some tissues IPSP or closes K+ channels in others EPSP. -In the heart, K+ channels are opened, creating IPSPs hyperpolarization that slow the heart rate. -In the smooth muscles of the stomach, K+ channels are closed producing EPSPs depolarization and the contraction of these muscles.

*Neurotransmitters

-Language of nervous system -50 or more neurotransmitters have been identified -Classified by chemical structure and by function -ACH -Monoamines (NE, Epi, Dopamine, Serotonin, Histamine) -Amino acids Excitatory (glutamate) Inhibitory (GABA, glycine) -Others

Altering Membrane Potential

-Neurons and muscle cells can change their membrane potentials: Called excitability -Caused by changes in the permeability to certain ions; Ions will follow their electrochemical gradient = combination of concentration gradient and attraction to opposite charges. -Flow of ions: Ion currents in limited areas where ion channels are located

*Resting Membrane Potetial

-Neurons have a RMP of −70mV. •Established by large negative molecules inside the cell •Na+/K+ pumps maintains it •Permeability of the membrane to positively charged, inorganic ions •At rest, there is a high concentration of K+ inside the cell and Na+ outside the cell.

*Two Types of Acetylcholine Receptors

-Nicotinic ACh receptors -Muscarinic ACh receptors

All-or-None Law

-Once threshold has been reached, an action potential will happen. -The size/strength of the stimulus will not affect the amplitude of the action potential; it will always reach +30mV. -The size of the stimulus will not affect action potential duration.

Norepinephrine as a neurotransmitter

-Released in both the CNS and PNS -Sympathetic neurons of the PNS use norepinephrine on smooth muscles, cardiac muscles, and glands. -Used by neurons of the CNS in brain regions associated with arousal -Amphetamines work by stimulating norepinephrine pathways in the brain. Amphetamine is used to treat narcolepsy and attention deficit disorder with hyperactivity ADHD.

ACh in the PNS

-Somatic motor neurons form interactions called neuromuscular junctions with muscle cells. -The area on the muscle cell with receptors for neurotransmitter is called the motor end plate. -End plate potentials open voltage-gated Na+ channels, which result in an action potential. This produces muscle contraction.

*Astrocyte Functions

-Take up K+ from the ECF to maintain ionic environment for neurons -Take up extra neurotransmitter released from axon terminals, particularly glutamate. Chemicals are recycled. -End-feet around capillaries take up glucose from blood for use by neurons to make ATP -Can store glycogen and produce lactate for neurons to use -Needed for the formation of synapses in the CNS -Regulate neurogenesis in regions of the adult brain -Release transmitter molecules gliotransmitters that can stimulate or inhibit neurons -Form the blood-brain barrier

Serotonin as a neurotransmitter

-Used by neurons in the raphe nuclei middle region of brain stem •Implicated in mood, behavior, appetite, and cerebral circulation •The drug LSD and other hallucinogenic drugs may be agonists. •Serotonin specific reuptake inhibitors SSRIs are used to treat depression. Prozac, Paxil, Zoloft Over a dozen known receptors allow for diversity of serotonin function. Different drugs that target specific serotonin receptors could be given for anxiety, appetite control, and migraine headaches.

Channel activities during Action Potentials

1)Na+ voltage-gated channels open if the membrane potential depolarizes to −55mV =threshold. 2)Na+ rushes in due to the electrochemical gradient. As the cell depolarizes, more Na+ channels open, and the cell becomes more and more permeable to Na+ positive feedback loop. These channels are deactivated at +30mV. 3)At around +30mV, voltage-gated K+ channels open, and K+ rushes out of the cell. This makes the cell repolarize negative feedback loop. 4)Repolarization actually overshoots resting potential and gets down to −85mV hyperpolarization. 5)Na+/K+ pumps quickly reestablish resting potential.

Oscilloscope

A piece of test equipment used to view and measure a variety of different waveforms.

Blood-Brain Barrier BBB

A tightly regulated interface in the CNS that regulates the exchange of chemicals in and out from the brain thus maintaining the CNS homeostasis. -Capillaries in the brain do not have pores between adjacent cells but are joined by tight junctions. -Substances can only be moved by very selective processes of diffusion through endothelial cells, active transport, and bulk

Possible drug effects on synaptic effectiveness:

A. release and degradation of the neurotransmitter inside the axon terminal. B. increased neurotransmitter release into the synapse. C. prevention of neurotransmitter release into the synapse. D. inhibition of synthesis of the neurotransmitter. E. reduced reuptake of the neurotransmitter from the synapse. F. reduced degradation of the neurotransmitter in the synapse. G. agonists evoke same response as neurotransmitter or antagonists (block response to neurotransmitter) can occupy the receptors. H. reduced biochemical response inside the dendrite.

Botox

ACH antagonist Medically to treat certain muscular conditions; Cosmetically to remove wrinkles by temporarily paralyzing muscles. It is made from a neurotoxin called botulinum toxin that is produced by the bacterium Clostridium botulinum.

Curare

ACH antagonist => blocks ACh receptors => muscles do not contract. -Leads to paralysis and death due to paralyzed diaphragm -Used clinically as a muscle relaxant

*Acetylcholine (ACh)

ACh is a neurotransmitter that directly opens ion channels when it binds to its receptor. -In some cases, ACh is excitatory, and in other cases it is inhibitory, depending on the organ involved -Excitatory in some areas of the CNS, in some autonomic motor neurons, and in all somatic motor neurons -Inhibitory in some autonomic motor neurons

ACh in the CNS - Alzheimer's Disease

Associated with loss of cholinergic neurons that synapse on the areas of the brain responsible for memory -Age related - affecting intellectual functions & memory loss -Treatment: Cholinesterase inhibitors=> more ACH available

Structural Classification of Neurons

Based on the number of processes that extend from the cell body.

Norepinephrine Action & G-proteins

Binding of a catecholamine to its receptor activates a G-protein to dissociate and send the alpha subunit to an enzyme called adenylate cyclase which converts ATP to cAMP cAMP activates an enzyme called protein kinase, which phosphorylates other proteins. An ion channel opens.

Chemically Regulated Channels

Binding of a neurotransmitter to a receptor can open an ion channel in one of two ways: Ligand-gated channels G-protein coupled channels

Nerve

Cable like collection of many axons in the PNS; may be "mixed" *contain both sensory and motor fibers

Muscarinic ACh receptors

Can be stimulated by muscarine from poisonous mushrooms Found in CNS and plasma membrane of smooth and cardiac muscles and glands innervated by autonomic motor neurons

Neurolia (glial cells)

Cells that are non-conducting but support neurons

Interruption of Neuromuscular Transmission

Certain drugs can block neuromuscular transmission Curare ACH antagonist Botox ACH antagonist

Nervous tissue

Composed of - Neurons - Glial cells

Autonomic motor nerve

Definition- Nerve that stimulates contraction or inhibits contraction of smooth muscle and cardiac muscle and that stimulates glandular secretion Function-innervate involuntary targets such as smooth muscle, cardiac muscle, and glands Sympathetic and Parasympathetic

*Somatic motor nerve

Definition- nerve that stimulates contraction of skeletal muscles Function- responsible for reflexes and voluntary control of skeletal muscles

*Nervous System

Divided in to - CNS/Central Nervous System - PNS/Peripheral Nervous System

Relative refractory period

During this period, a stronger-than-normal depolarizing potential is needed to bring the cell up to the threshold for an AP.

Synapses: Electrical & Chemical

Electrical synapses in smooth & cardiac muscle, & between some neurons of the brain; Cells are joined by gap junctions. Stimulation causes phosphorylation or dephosphorylation of connexin proteins to open or close the channels Chemical synapses involve the release of a chemical called a neurotransmitter from the axon's terminal boutons. The synaptic cleft is very small, and the presynaptic and postsynaptic cells are held close together by cell adhesion molecules (CAMs).

Refractory Periods

Ensures that each AP is an all-or-none event& enforces one-way transmission of nerve impulses

Nodes of Ranvier

Gaps between Schwann cells, called nodes of Ranvier, are left open.

Neurons

General functions -Respond to chemical and physical stimuli -Conduct electrochemical impulses -Release chemical regulators -Enable perception of sensory stimuli, learning, memory, and control of muscles and glands -Most can not divide by mitosis, but can repair

Myelin Sheath - CNS

In the CNS, the myelin sheath is produced by oligodendrocytes.

Action Potential Conduction Speed

Increased by: Increased diameter of the neuron. This reduces resistance to the spread of charges via cable properties. Myelination because of saltatory conduction Note: Multiple sclerosis MS is the loss of myelin at one or more places in NS => slows or blocks the propagation!

Myein sheath

Located: in the PNS

Monoamines

Monoamines are regulatory molecules derived from amino acids Catecholamines: derived from tyrosine; include dopamine, norepinephrine, and epinephrine Serotonin: derived from L-tryptophan Histamine: derived from histidine

Association neuron/ Interneuron

Multipolar neuron located entirely within the CNS

*White matter

Myelin gives these tissues (axons) a white color

Conduction in a Myelinated Neuron

Myelin provides insulation, improving the speed of cable properties. .Nodes of Ranvier allow Na+ and K+ to cross the membrane every 1−2 mm. .Action potentials "leap" from node to node. This is called saltatory conduction.

Multiple Sclerosis MS

Neurologic disability; autoimmune condition Myelin sheaths in CNS destroyed Immune system attacks myelin Turns it to hardened lesions called scleroses Impulse conduction slows and eventually ceases Symptoms Visual disturbances, weakness, loss of muscular control, speech disturbances, and urinary incontinence Treatment Drugs that modify immune system's activity improve lives

*Sensory neuron/Afferent neuron

Neuron that transmits impulses from a sensory receptor in the CNS

*Motor neuron/Efferent neuron

Neuron that transmits impulses from the CNS to an effector organ; for example, a muscle

Dopamine as a neurotransmitter

Neurons that use dopamine (dopaminergic neurons) are highly concentrated in the midbrain in two main areas: -Nigrostriatal dopamine system: involved in motor control -Mesolimbic dopamine system: involved in emotional reward

Actions of Neurotransmitter

Neurotransmitter diffuses across the synapse, where it binds to a specific receptor protein. -The neurotransmitter is referred to as the ligand. -This results in the opening of chemically regulated ion channels (also called ligand-gated ion channels).

Release of Neurotransmitter

Neurotransmitter is enclosed in synaptic vesicles in the axon terminal. The Ca2+ synaptotagmin complex displaces part of SNARE, and the vesicle fuses

* Absolute refractory period

Once an AP has begun about 1 msec, a second AP cannot be triggered

Neurons

Structural and functional units of the nervous system

G-Protein Coupled Channels

The neurotransmitter receptor is separate from the protein that serves as the ion channel. -Binding at the receptor opens ion channels indirectly by using a G-protein. -Muscarinic ACh receptors interact with ion channels in this way as well as dopamine and norepinephrine receptors

Ligand-Gated Channels

The receptor protein is also an ion channel; binding of the neurotransmitter directly opens the ion channel. Nicotinic ACh receptors are ligand-gated channels with two receptor sites for two AChs. Binding of 2 acetylcholine molecules opens a channel that allows both Na+ and K+ passage. Na+ flows in, and K+ flows out.

Graded Potential

When ligand-gated ion channels open, the membrane potential changes depending on which ion channel is open. -Opening Na+ or Ca2+ channels results in a graded depolarization called an excitatory postsynaptic potential EPSP. -Opening K+ or Cl− channels results in a graded hyperpolarization called inhibitory postsynaptic potential IPSP e.g. barbiturates, alcohol.

Central nervous system

brain and spinal cord

* Retrograde transport

from dendrites and axon to the cell body

Sheath of schwann

cells wrap around the axon to form the myelin sheath in the PNS

Myelinated axons

conduct impulses more rapidly.

Agonists

drugs that can stimulate a receptor •Nicotine for nicotinic ACh receptors •Muscarine for muscarinic ACh receptors

Antagonists

drugs that inhibit a receptor •Atropine is an antagonist for muscarinic receptors. •Curare arrow poison originating from South America is an antagonist for nicotinic receptors.

Sympathetic

emergency situations; "fight or flight"

* Anterograde transport

from cell body to dendrites and axon

*Gray matter

is cell bodies and dendrites which lack myelin sheaths

*Astrocytes

most abundant glial cells in the CNS -Processes with end-feet associate with blood capillaries and axon terminals -Influences interactions between neurons and between neurons and blood -Although astrocytes do not produce action potentials, they are excited by changes in intracellular Ca2+ concentration. -When some neurons are active, they release ATP, which increases the Ca2+ of adjacent astrocytes; creates a Ca2+ wave -A rise in Ca2+ can also cause the astrocyte release prostaglandin E2 from the end-feet on a blood capillary, increasing blood flow.

Parasympathetic

normal functions; "rest and digest"

Dendrites

receive impulses and conduct the impulse toward the cell body

*Multipolar neurons

several dendrites and one axon; most common type

*Pseudounipolar

single short process that branches like a T to form 2 longer processes; sensory neurons

Neurons

that conduct impulses but generally can not divide.

Glial cells /neuroglia

that support the neurons and can not conduct impulses but can divide by mitosis - explains why brain tumors are composed of neuroglia! -Cells that are non-conducting but support neurons

Nigrostriatal Dopamine System

•Neurons from the substantia nigra part of the basal nuclei of the brain send dopaminergic neurons to the corpus striatum. •Important step in the control and initiation of movements •Parkinson disease is caused by degeneration of these neurons. •Patients are treated with L-dopa and MAOIs monoamine oxidase inhibitors.

Mesolimbic Dopamine System

•Regions of the midbrain send dopaminergic neurons to regions of the forebrain. •Involved in emotional reward systems and associated with addictions such as nicotine, alcohol, and other drugs •Schizophrenia is associated with too much dopamine in this system. •Drugs that treat schizophrenia are dopamine antagonists.

* Conduction of Nerve Impulses

•When an action potential AP occurs at a given point on a neuron membrane, voltage- gated Na+ channels open as a wave down the length of the axon. •The AP at one location serves as the depolarization stimulus for the next region of the axon