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ANNOUNCEMENTS

Monday, Oct. 25th Dr. Rebecca Levy

Interested in Lunch with Levy?

Join the Luncheon Lottery

Review Session Every Friday at 12:20

Lab Practical Coming up! October 26th, 27th

Motor Neuron

Nerve Action Potential

Synapse

Neuromuscular Junction

Neurotransmitter (ACh)

Receptors (AChR)

Muscle Action Potential

Transverse Tubules

Sarcoplasmic Reticulum

Calcium release

Smooth Muscle •! Spindle shaped (fusiform) •! Nonstriated (smooth)

- Contractile proteins are less organized •! Contractile proteins anchored at densities

- Contractile proteins bind to Dense Bodies

•! Gap Junctions between cells

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Smooth Muscle

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Smooth Muscle Contraction

- Actin filaments are associated with tropomyosin but Not Troponin

Smooth Muscle Contraction -Myosin interacts with actin only when the

myosin light chains are phosphorylated

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cell&part=A4335

Smooth Muscle Excitation-Contraction

1) Excitation=> increased [Ca++]intracellular

2) Ca++ binds Calmodulin

3) Ca++-Calmodulin activates myosin light chain kinase (MLCK )

4) MLCK phosphorylates myosin light chains

5) Myosin binds actin => contraction

Regulation of Smooth Muscle Contraction

Nonneural regulation

Hormonal: Oxytocin- uterine contraction

Nitric Oxide (NO): Produced by endothelial cells of arterioles Relaxes smooth muscle

Mice have been produced whose eNOS (endothelial cell NO synthase) genes been "knocked out”. Predict the blood pressure levels of these mice.

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Nitric Oxide ----> increased [cGMP]

activates a kinase

inhibits Ca++ influx into smooth muscle cell

decreased calcium-calmodulin stimulation of MLCK

decreased phosphorylation of myosin light chains

decreased smooth muscle tension development

vasodilation (expansion of vessel lumen)

Predict the effect of drugs that inhibit

breakdown of cGMP ?

Drugs that inhibit the breakdown of cGMP potentiate (increase) the effects of NO

actions on target cells.

EXAMPLE: Viagra and other inhibitors of cGMP-dependent phosphodiesterase

Nervous System

Functions: –!Input from sensory receptors

–!Integration and processing of signals

–!Output to effector cells

–!Behavior

Neurons

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Neurons have dendrites, a cell body & an axon. Neuronal Structure: –!Cell body

Nissl substance

Nucleus/nucleoi

organelles

–!Axon •!Axon Hillock (initial segment)

•!Ion channels

•!Sometimes myelinated

Anterograde Cell body!Axon terminal Motor= Kinesin

Retrograde Axon terminal!Cell body Motor= Dynein

Axonal transport

Nervous System Structure:

–!Dendrites Dendritic spines

Synaptic input

www.neuro.duke.edu/.../ media/3381036764_t.gif

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Normal Fragile-X Syndrome

Dendritic Spines

Density and shape influenced by:

-activity

-environment

-age

-lead exposure

- genetics/disease

- drug use Left panel: Portions of apical dendrites of layer V pyramidal cells of the visual cortex in a normal 48-day-old mouse stained with the Golgi method.

Right panel: Apical dendrites of pyramidal cells in the visual cortex of mice reared in complete darkness for 48 days since birth.

www.cajal.csic.es/ valverde/spines.htm

Synapse: Chemical Synaptic Transmission

Presynaptic terminal

Synaptic vesicles

Neurotransmitter

Synaptic cleft

Postsynaptic Membrane

Neurotransmitter Receptors

Postsynaptic density

http://starklab.slu.edu/neuro/synapse.jpg

synapses.mcg.edu/ atlas/1_4_1_20.gif

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Electrical Synaptic Transmission

NO SYNAPTIC VESICLES

Gap Junction (Connexons)

Chemical Transmission

Electrical Transmission

Myelin sheath Function: increase speed of action potential

propagation (saltatory conduction)

Produced by Glial cells •! Schwann cells- motor & sensory neurons •!Oligodendrocytes- brain & spinal cord

Nodes of Ranvier

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Node of Ranvier

Sciatic nerve axon:

sodium channels (TTX)

potassium channels (Kv1.2) (TEA) caspr (contactin-associated

protein: mediates interactions

between Schwann cell and axon)

www.urmc.rochester.edu/. ../sciatic_node.gif

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Peripheral Nerve: Schwann cells wrap axons

- MYELINATED Myelin sheath 1 axon/Schwann cell

-UNMYELINATED No myelin sheath Multiple axons/Schwann cell

Oligodendrocytes form myelin in CNS

-! glial cell

-! myelinates CNS axons

-! multiple axons/ oligodendrocyte

-! NOT associated with unmyelinated axons

Multiple Sclerosis

gamma-interferon

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What are the consequences of cutting the axon of a neuron?

Consider: Transmission of action potential Composition of synapses Structure of damaged neuron

Axonal damage influences target and input cells.!

Muscle Atrophy

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CNS: Limited Regeneration

Unlike PNS axons, after CNS axon damage: •!neurons die •!growth of regenerating axons is inhibited •!lack of environmental growth factors

Glial Scar Formation: Astrocyte and microglia

Myelin contains growth-inhibiting proteins: Nogo-A MAG (myelin-associated glycoprotein) Bind to Nogo receptor (NgR)

Approaches to improve CNS regeneration:

1) Prevent neuronal death -!Limit inflammatory response

2) Induce CNS axon growth -!Implant Schwann cells or PNS nerve -!Implant Olfactory ensheathing cells

3) Overcome inhibitory environmental factors -! prevent or impede scar formation -! block activity of Nogo-A and MAG

RELEASE OF SYNAPTIC VESICLES

Botulinum toxin:

from Clostridium botulinum

prevents neurotransmitter release by proteolytically cleaving proteins required for vesicle release

RELEASE OF SYNAPTIC VESICLES

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A: A patient with blepharospasm, forceful involuntary closure of the eyelids, is unable to open her eyes due to abnormal muscle contractions.

B: Pre-injection, she uses her fingers to keep her eyes open.

C: After Botox injection, her eyes stay open without difficulty. (Photos courtesy Joseph Jankovic, M.D., professor of neurology, Baylor College of Medicine, Houston, Texas)

A B C

users.rcn.com/.../ BiologyPages/P/PNS.html

Nervous System Organization

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Brain, Spinal cord

users.rcn.com/.../ BiologyPages/P/PNS.html

Peripheral Nervous System (PNS)

Autonomic PNS Somatic PNS Internal stimuli External stimuli parasympathetic/sympathetic (sensory-motor)

Groups of Neuronal Cell Bodies

CNS --> Nucleus (Gray matter) -functionally related

PNS --> Ganglion

Bundles of Axons

CNS --> Tracts (White matter)

PNS --> Nerves

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MENINGES

3 connective tissue membranes Cover brain and spinal cord

1)! Dura Mater: dense CT

3)!Arachnoid: web-like arachnoid trabeculae loose CT

subarachnoid space cerebral spinal fluid

3) Pia Mater ensheathes blood vessels

Meninges

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Cerebral Spinal Fluid (CSF) -! Clear fluid

- Circulates through ventricles & subarachnoid space

- Produced by choroid plexus •!modified ependymal cells •!lining ventricles

-!Functions: -!“shock absorber” -!transport nutrients / waste -!compensate for changes in brain blood volume

Choroid Plexus Cuboidal-Columnar Ependymal Cells neighbor capillaries to form the choroid plexus that produces the cerebral spinal fluid

Production of CSF = Absorption of CSF into blood

Blocked CSF flow or overproduction of CSF results in hydrocephalus.

Hydrocephalus: excess CSF accumulation in brain

Hydrocephalus: excess CSF accumulation in brain

Treatment: shunting of CSF into abdominal cavity

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MENINGITIS

-! infection / inflammation of meninges and CSF

Infectious Agents: Viruses Bacteria pneumococcus: blood->meninges meningococcus: respiratory->blood

(college epidemics)

Signs or symptoms: * High fever * Severe headache * Stiff neck * Sensitivity to light * Seizures

DORSAL ROOT GANGION

AUTONOMIC NERVOUS SYSTEM

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Ganglion Neurons

- capsule

dense irregular CT

- satellite cells

cuboidal glial cells

Nerve Fascicles Axon

Epineurieum Perineurium Endoneurium

Epineurieum Perineurium Endoneurium Glial cells •!Schwann cells / Satellite cells

•!Oligodendrocytes

•!Ependymal cells

•!Astrocytes

•!Microglia CNS

PNS

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Astrocytes - largest glia cell - many long processes

- form ”perivascular feet" on capillaries - line surface of CNS (glial limitans) - cap nodes of Ranvier

Functions:

- support neurons

- maintain the [ion] and pH of extracellular fluid

- contribute to blood-brain-barrier

- remove neurotransmitters from synaptic cleft

Protoplasmic Astrocytes

-! in gray matter -! mixed thick and thin processes; fuzzy -! ellipsoid or bean-shaped nucleus

Fibrous Astrocyte

- in white matter

-! thinner processes

-! 80% adult primary brain tumors

Blood Brain Barrier

limit permeability across capillary epithelium

-! tight junctions

-! astrocytic processes

-! gases and sugars

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Challenge: limited access of drugs and therapeutic molecules

Solution: Selectively open barrier (cancer treatment) Couple transport with permeable compound

Microglia

-! smallest, infrequent glial cell

-! short twisted processes

-! act as macrophages, remove debris

-! proliferate & become phagocytic after damage