Chapter 1 and 2 of Neurology

Chapter 2: Neurons and Glia

History of neuroscience

Where is the seat of intelligence

• Ancient Egyptians= proposed that the heart was the seat of intelligence

• Aristotle= The role of the brain is to cool the blood

• 1600s= Gall= phrenology= behavioral traits could be inferred from bumps on the skull reflecting brain enlargements

• 1861= Dr. Paul Broca= studied patients unable to speak but they could understand language. They had a legion in the same part of the brain (now coined as the Broca area) which is important for language

• 1891= Dr. Carl Wernickle= studied patients that could speak but could not understand language

  • It had legions but just in a different part of the brain

• Now: some functions are localized but others aren’t

How does information pass through nerves and move muscles?

• Galen: discovers the brain’s fluid filled ventricles. Proposes that the nervous system operates via hydraulics

• Descartes= agreed with Galen’s sentiment

• Mid-1700s= Electricity is discovered→ Luigi Galbani demonstrated this is how neves and muscles work via electricity.

Debate: Is the nervous system a continuous “reticulum” or cells?

• Late 1800s/Early 1900s

  • Golgi= argues that nervous system is a continuous reticulum like the circulatory system

  • Ramon y Cajal= argues that it’s made of cells that communicate via contact

    • Cajal= used silver nitrate stain (Golgi stain) Golgi developed to prove he was right and Golgi was wrong

    • Settled in 1950s with the help of the electron microscope

  • Neuron doctrine= the fact that the nervous system is a selection of cells called neurons

• Nerve cell communication

  • Sparks= Information travels down n erve cells with electricity. This is how neurons communicate (how the gap closed)

  • (Correct theory) Soups= Information travels down nerve cells with electricity. But the connection is crossed via chemicals

  • Dominant framework in neuroscience since 1960s

    • Molecules → neurons & circuits → brain function and dysfunction

    • Genes >> proteins >> neurons>> circuits (brain activity) >> mind and behavior

      • E.g. Huntington Disease

        • Genetic mutation >> toxic proteins >> neurons die >> motor mood and cognitive impairment

        • Problems at the molecular level leads to problems at highest level

      • Dominant framework

        • genes → proteins→ neurons → circuit → brain activity→ mind and behavior

    • Genes: code for proteins that are used to form and operate neurons. They then form a network of circuits to communicate info which is called brain activity, which dictate mind/behavior

Neurons and Glia

• Histology

  • Brain cells→ neurons and glia are very small

    • Size of brain cells 10-50 micrometers

  • Cannot be seen by the naked eye

  • Compound microscope (17th century) allowed the field of cellular neuroscience to begin

  • Brain tissue is similar to jello and cannot be sliced into sections unless hardened

  • Usually harden with formaldehyde and sliced with microme

  • It is uniform under a microscope

  • Nissil stain= primarily stains neurons not glia

    • Stains the cell body

    • I.e. not the hest stain does not show complete cytoarelinetine which is the arrangement of cells

  • Camillo Golgi

    • Golgi Stain 1873

    • Silver chromate solution

    • Two parts of neurons

      • Cell body= soma

      • Neurites= axons and dendrite

      • 

    • Santiago Ramon y Cajal

      • Used the Golgi stain 1888 and a light microscope to see and draw neurons and neural circuits

      • The neuron doctrine

        • Neuron is the basic functional unit of the nervous system

        • Cell theory applies to neurons

        • Contact, not continuity

        • Cell theory= the belief that the system is made of a collection of cells than a continuous reticulum

      • Cajal and the Neuron Doctrine

        • Neurons are discrete cells

        • Connected but not continuous

        • Synapse is 20-50 mm

    • Difference between axons and dendrites

      • Axons are the way a neuron sends outgoing signal

      • Dendrites are where a neuron receives a signal

      • Specificity to the connections among neurons

      • Unidirectional information flow

    • Basics of a neurons

      • Neurons sense changes in the environment, communicate them to other neurons and command the body’s response to the stimulus

    • Properties of neurons

      • Morphologically heterogeneous in size and shape each has a unique size/shape

      • Conduct bioelectric signals across long distances with no toss of signal strength

      • Possess specific connections with other nerve cells and with muscles and glands

        • Specific neurons are connected to specific efforts the connections aren’t arbitrary

        • Protoypical neurons

Three parts

Soma: cell body; contains nucleus and other organelles

Performs most metabolic functions

Dendrites- projections from the soma that information

Axon; extension that sends information- via electrical signals from the cell body to the terminal buttons (transmits away)

Usually has one acon it may branch to form axon collaterals

• Soma and its contents

  • Nucleus: contains DNA, which is transcribed into mRNA and translated into a protein

  • Chromosomes>> DNA

  • Gene expression: DNA → transcription→ mRNA

  • RNA processing (alternative splicing 1 gene > multiple proteins)

    • mRNA exists nucleus via pores in nuclear envelope for translation into protein

  • Nucleus Structure

    • Roughly spherical with double membrane nuclear envelope with folded inner membrane

    • Reinforced with nuclear pores for exchange of materials e.g. nucleotides, mRNA etc

    • Pores are 0.1 um. Contains all genetic material as DNA condemned into chromatin threads, which contains genes that each code for specific proteins

  • Ribosomes and Rough Endoplasmic reticulum (ER)

    • Ribosomes: proteins translation: mRNA >> protein

    • Bound ribosomes >> Rough ER

Aka. Nissl bodies: membrane with attached ribosomes (bound ribosomes)

Translated proteins inserted into plasma membrane or are exocytosed (ion channels)

Also they are packet in lysosomes

Lots in neurons

• Free ribosomes

Translates proteins that are released into the cytosol

• Smooth ER and Golgi Apparatus

Smooth ER: no ribosomes

Folds proteins giving them 3D structure

Regulates internal Ca2+ concentration

Golgi apparatus

“Post translational” modification of proteins

“Post office” sorts proteins destinations

• Mitochondria

Site of cellular respiration

“Powerhouse”

Kreb’s cycle yield ATP, the cell’s energy source

Neurons require large amounts of ATP

Mitochondria are especially abundant where energy needs are greatest

Concentrated at synapses- neurotransmitter synthesis

• Rough ER structure

Network of tubular membranes enclosing fluid filled sacs called eisternae each

1-1.5 um

Contains receptors to which ribosomes attach

• Ribosome structure

Made of rRNA 2 subunit (1 small 1 big) contains peptidyl site, amino deysite and E site

• Structure of smooth ER

More tubular than RER. modifies and transports lipid and helps 3’ folding of proteins

It regulates Ca 2+ in muscle cells → sarcoplasmic reticulum

• Structure of Golgi apparatus

Stacks of flattened fluid filled sacs called cisternae. CONVEX: forming face where vesicles containing materials to modify enter. CONCAVE: maturing face, when vesicles with modified material huf off

• Structure of mitochondria

1 um thick to 10 um in length

Double membrane envelope

Inner membrane folded cristae which increases SA for phosphorylation; impermeable to ions to set up electrochemical gradient for ATP synthesis

Contains circular DNA for binary fission not enclosed in a nuclear membrane, free in the matrix (bachynoid fluid), not associated with histones, 70s ribsomes for protein synthesis

• Neural membrane structure

selectively permeable phospholipid bilayer controls exchange of materials between cell and environment

Contains protein channels carriers and pumps (K+/Na+)

Many of which are voltage gated which help to set of action and resting potential for transmitting impulses.

Cytoskeletal Proteins in Neurons

The Axons (sends info)

• No rough ER or free ribosomes

• Membrane proteins are quite different

  • Axon hillock (beginning) where axons tanners away from soma

  • Axon proper (middle)

    • Collaterals (branches) = increase surface area

  • Axon terminal (end)

    • “Terminal bouton”

    • “Nerve terminal” (synaptic bulb)

      • Used for communication

    • Axon collaterals that branch and then return to communicate with original neurons are called cecurrent axon collaterals

Axon terminal

• Presynaptic side

• Presence of synaptic vesicles (w/ neurotransmitter (NT))

• Large number of mitochondria (high demand)

• Synaptic bulb heavily coated in proteins

• When a neuron makes contact with another cell it is called innervation

The Synapse (gap between neurons)

Two sides

1. Presynaptic membrane

   1. Filled with NT vesicles

2. Postsynaptic membrane

   1. NT receptors inserted into membrane

   2. Synaptic cleft= the space between

      1. NT is released into here

   3. Synaptic transmission= transfer of info at the synapse

      1. Electrical to chemical to electrical: transfer of info at the synapse

Axoplasmic Transport

• No protein translation in axon→ all protein is made in the soma

• Axoplasmic transport: proteins made in the soma must be transported to the axon terminals

• Uses the cytoskeleton

  • MT form the track along which packets of proteins travel by the action of motor proteins (kinesin & dynein)

• Anterograde→ away froom the soma

  • Soma to axon terminal

  • Uses kinesin

• Retrograde→ back to soma

  • Axon terminal to soma

  • Uses dynein

• Dendrites (receive information)

  • “Antennae” of neurons

  • Dendritic “tree” aborization

    • collective= dendritic tree

    • 1 branch= dendrite

  • Covered with neurotransmitter receptors

  • High ribosome content

    • Protein synthesis

  • Some covered with spines

    • Like leaves on a tree, increase surface

• Dendritic spines

  • Described by Cajal in 1888 “brisitiling thorns or short spines”

  • “Leaves on the trees”

  • Contain neurotransmitter receptors

  • Form, enlarge, shrink, and retract throughout the animal’s lifespan

    • Dynamic in nature

    • Branching from original branch dendrite in the tree especially

    • Dendritic spines are induced in development to ensure neurons are connected to correct neurons

• There are some exceptions to this

  • Axons can be connected to other axons

Classifying neurons

• Based on the number of neurites (axons and dendrites) on soma

• 

Based on connections

• Motor neurons

  • Direct output to muscles

• Primary sensory neurons→ they have connections with receptors

  • Convert physical stimuli (like light or sound or pressure) into electrical signals

• Interneurons

  • Connections only with other neurons in brain spinal cord

    • Do not make connections outside of PNS and CNS

Based on dendritic or somatic morphology

• Stellate cells → can be spiny or aspinous

• Pyramidal cells→ always spiny

Based on axonal length

• Golgi type 1: long axons → projection neuron→ axon extend from 1 side of brain to other

  • Pyramidal cells

• Golgi type 2: short axons→ axon doesn’t extend beyond

  • Stellate cells

Based on neurotransmitter type

• Ex: glutamatergic: releases glutamate at synapses

• Ex: dopaminergic: releases dopamine at synapses

• Ex: cholinergic: release acetylcholine at synapse

• MB: Every neuron will make for unique proteins or neurotransmitters for their corresponding receptors

Glia: The Glue that holds it altogether

• Contribute to brain function in a supporting role. They act as insulators, nourish and support neighboring neurons and within spaces to limits neurite growth

• Glia

  • Outnumber neurons 10 to 1

    • Support neuronal functions

      • Formation of synapses and development

      • Neuronal plasticity

      • Protection against neurodegeneration and toxicity

      • Response to i injury

      • Neurotransmission

  • Types of glia

    • Astrocytes

    • Oligodendrocytes

    • Ependymal cells

    • Microglia

Astrocytes

• Most numerous glia in the brain

  • Envelop synapses

  • Neurotransmitter reuptake

• Influence neurite growth (radial glia) → subtying glia

Myelinating glia

• Produce myelin sheath that insulates axons

  • Schwann cells (peripheral NS)

    • One cell myelinates a single axon

  • Oligodendrocytes (central NS)

    • One cell can myelinate several axons

      • (probably due to density of neurons in CNS)

      • Lactating at Nodes of Ranvier

      • Allows propagation of action potential across the axon for faster transmission

  • Microglia

    • “Immune system of the brain”

    • Respond to insult or injury in the CNS

    • Microglial activation and motility following brain tissue injury

    • They act as phagocytes or repair the brain

  • Ependymal cells

    • Line the brain’s ventricular system

    • Produce cerebrospinal fluid CSF