Nervous System Part I: Central Nervous System

Central Nervous System (CNS)

• Brain

• Spinal cord

Peripheral Nervous System (PNS)

• Spinal nerves

• Autonomic nerves

• Enteric nerves

Cerebral Hemisphere

• Four Anatomical Lobes:

  • Frontal

    • Executive function

    • Motor

  • Parietal

    • Sensory info (pain, touch)

  • Occipital

    • Vision (motion, color perception, contrast)

  • Temporal

    • Sound

      • Distinguishing sound

      • Language

    • Memory

    • Object/facial recognition

Nervous System (Sensory)

• Nervous system is comprised of sensory receptors

  • Detect stimuli in the external environment

• Steps of transfer:

  • Spinal cord

  • Medulla, pons, mesencephalon

  • Cerebellum

  • Thalamus

  • Cerebral cortex

Nervous System (Motor)

• Controlled by:

  • Contraction of appropriate skeletal muscles throughout the body

  • Contraction of smooth muscle in the internal organs

  • Secretion of active chemical substances

    • Exocrine

    • Endocrine

  • Muscles and glands = effectors

Neuronal Development

• 3rd week of development: outermost layer of embryo (ectoderm) thickens to form neural plate

• Plate develops → longitudinal groove flanked by neural folds

• Neural fold fuse → tube-like structure

  • Process = neurulation

  • Form = neural tube

• Cell proliferation from neural tube gives rise to CNS

• Cel proliferation from migratory neural crest cells for PNS

Neuron

Nerve cells & glial cells are primary cellular components of nervous system

Neuron (Cell Body)

• Major organelles:

  • Nucleus, Golgi apparatus, Nissl substances (rich in protein concentration), cytoskeleton, mitochondria

• Primary functions:

  • Synthesize macromolecules

  • Integrate electrical signals

Neuron (Dendrites)

• Extensions of cell body

• Major organelles: cytoskeleton & mitochondria

• Primary functions: collect info from other neurons

Neuron (Axon)

• Single, cylindrical, myelinated (CNS) v. In myelinated (PNS)

• Organelles: cytoskeleton, mitochondria, transport vesicles

• Functions: Conduct info to other neurons

Neuron (Axon Terminals)

• Vesicle-filled apposition to part of another neuron

• Synaptic connections: axodendritic, axosomatic, axoaxonic

• Organelles: synaptic vesicles, mitochondria

• Functions: transmit info to other neurons

Small Molecules

• Ex: Amines or AA

• Synthesized in presynaptic cytoplasm

  • Locally available substrates (Ex: acetate & choline)

  • Soluble enzymes that arrive by slow atonal transport

Neuropeptides

• Synthesized in neuronal cell body

• Packed into vesicles & dispatched by fat axonal transport

• Ex: Angiotensin II: Promotes water retention (larger molecules)

Amino Acids

• Glutamate: major transmitter for ESPS in the CNS

• GABA & Glycine: ISPS in the CNS

Amines

• Acetylcholine: Muscle contraction

Intracellular Transport in Neurons

• Kinesin family proteins (KIFs) transport organelles anterogradely: KIF3, KIF17

• Cytoplasmic dynein & KIF2 transport retrogradely

• Small molecule NT synthesize in axon terminal

• Large-molecule NT synthesized in Cell Body

Diffusion

• Utilizes a concentration gradient

• Movement of ions from HIGHER concentration to LOWER concentration

Electrical Potential

• Force exerted on a charged particle

• Opposites attract v. Same repels

Gating Channels

Types: Ca 2+, K+, Cl-, Na+

Voltage-gated

Respond to appropriate voltage changes

Ligand-gated

• Respond to binding of signaling molecule

• Need binding site to allow channel to open up

Action Potentials Along the Axon

• Voltage-gated channels are closed (K+ > Na+)

• Depolarization: causes Na+ voltage channels to open

• Na+ channels inactive, K+ open

• K+ efflux repolarize the membrane

• K+ are slow to close during hyperpolarization (Na+ opening)

Propagation of the AP

1. Glutamate

2. Bind to postsynaptic receptors

3. Open

4. Na+ comes in, K+ leave (Change in current; depolarize neuron)

5. Drive ionic composition (more positive)

6. Threshold (more positive, less negative)

7. Current flows through axon

8. Ca2+ channels open

9. Ca enters neuron

10. Ca causes NT to fuse at synaptic cleft

11. NT released

12. NT binds onto specific receptors

13. Allow ions to flow into the cell

Neuronal Communication (Chemical)

• Chemical synapses: most common form of neuronal communication

• Single AP travels through axon & arrives at axon terminal

• Brief opening of voltage-gated Ca2+ channels increase in [Ca2+]

• Nearby vesicles fuse with presynaptic membrane

• Discharge contents into synaptic cleft; then recycled

Neuronal Communication (Electrical)

• Electrical synapses: gap junctions between neurons; connection between pre & post synapse

• Duplication of signal from pre- to post-

  • No delay in transmission

  • No vesicle syntheses needed

• Lack in functional heterogeneity (rare)

Excitatory Receptors in Postsynaptic Membrane

• Opening of Na+ channels to allow large numbers of positive electrical charges to flow to the interior of the postsynaptic cell

• Depressed conduction through Cl- or K+ channels or both

• Various changes in internal metabolism of postsynaptic neuron to excite cell activity

Inhibitory Receptors in the Postsynaptic Membrane

• Opening of Cl- channels through postsynaptic neuronal membrane (hyperpolarize)’Increase in conductance of K+ ions out of the neuron

• Activation of receptor enzymes that inhibit cellular metabolic functions, increase the number of inhibitory synaptic receptors or decrease the number of excitatory receptors

Excitatory Postsynaptic Potential (ESPS)

• Depolarization brings postsynaptic element closer to threshold for AP

• Both can be fast & slow

Inhibitory Postsynaptic Potential (ISPS)

• Hyper polarization moves membrane away from threshold for AP

• Both can be fast & slow

Clostridium Botulinum (Botox)

• Occurs at presynaptic terminal

• Cleaving of proteins involved in the fusion of synaptic vesicles with presynaptic membrane

• Prevent exocytosis of NT

• Prevent muscle contraction, shutdown presynaptic firing

Treatment of Myasthenia Gravis

• Autoimmune disease producing AB against one’s nicotine receptors

• Larger amounts of acetylcholine are hydrolyzed in synapse

• Patients become progressively weaker with repeated muscle contraction

• Less NT decrease in firing of postsynaptic neuron

Summation

• More synaptic connections firing can induce APs

• Increase in synapses if increase in synaptic clefts

• Spatial summation: # synaptic clefts

• Temporal summation: # firings

Gray Matter

Composed of cell bodies & dendrites (clumps) - nucleus

White Matter

Composed of axons (linear)

Glial Cells in CNS

• Support cells

• 10x more abundant than neurons in mammalian brain

• In CNS:

  • Oligodendrocytes ( CNS myelin sheaths)

  • Astrocytes

  • Ependymal cell

  • Microglia (prevalent in retina)

• Peripheral nerves:

  • Schwann cell (myelin production; electrical insulation)

  • Satellite cells (structural & metabolic support for neuronal cell bodies)

Dura Mater

Thick external layer of dense irregular connective tissue

Arachnoid

• Thin layer

• Composed of connective tissue & loosely arranged collagen & fibroblasts

• Subarachnoid space filled with CNS for protection (cushion)

Pia Mater

• Connection with cortex

• Flattened mesenchymal cells

• Separate CNS tissue of CSF

Arachnoid Villi

Release excess CSF into blood

Spinal Cord

• Gray Matter: neuronal cell bodies

• White Matter: axon tracts

• Posterior Horn: sensory neurons

• Anterior Horn: low motor neurons