Unit 1: Chemical Neurophysiology

• role of neurons: signaling for brain and nervous system
• role of glia: support cells that help neurons accomplish their functions
• connectome: map of all neurons in an organism and their connections
• c. elegans

  • the only species we know the full connectome of
  • over 300 neurons
  • less than 6000 connections (synapses)
  • 2000 connections between neurons and muscle (neuromuscular junctions)
• human nervous system:

  • 85 billion neurons
  • 100 trillion connections (synapses) between neurons
  • around 85 billion glia
• The brain has a Jello-like consistency, so brains are usually fixed in formaldehyde before slicing. This preserves and toughens the tissue.
• Sectioning is done on an instrument called a microtome. Fixed brains are embedded in paraffin wax and sliced in sections as thin as 20 µm.
• • It can be difficult to see cells on a brain slice. In order to see cells, stains were historically used. One such stain was invented by Camillo Golgi. He used silver to stain neurons.
  • Only a small percentage of brain cells are stained in a Golgi stain.
• • Santiago Ramón y Cajal used Golgi’s stain quite profitably. He drew his findings, producing these gorgeous images. These images helped solidify the “neuron doctrine,” the idea that the cells of the nervous system were discrete, separate units.
  • Prior to the work of Cajal and Golgi, many scientists believed that neurons were part of an interconnected “reticulum,” which enabled direct communication throughout the brain.
• Nissl Stain:

  • developed by Franz Nissl.
  • used basic dyes to stain brain slices.
  • dyes label DNA/RNA in both neurons and glia.
  • glia show up as small spots, representing their nuclei.
  • neurons show up as bigger structures—nuclei plus more diffusely stained structures called Nissl bodies.
• fluorescence microscopy:

  • another way to look at neurons is to use fluorescent tags or dyes.
  • a neuron can be filled with a fluorescent dye to visualize its structure.
  • Alternatively, specific proteins or structures in cells (DNA, membrane) can be fluorescently tagged.
• Electron microscopy (EM) uses an electron beam (instead of light) to look at cells.

  • This allows for much better resolution (0.1 nm or 10 -10 m), which helps to image finer structures in neurons and glia.
• Serial EM

  • also being used to map brain connections.
  • a piece of brain is sectioned by a microtome, each slice is imaged with EM and computers are use to stitch the images together.
  • this allows individual neurons to be traced
• nucleus:

  • a membrane-bound organelle that contains chromosomes.
  • chromosomes contain all of our genetic material in the form of DNA.
• endoplasmic reticulum:

  • a membrane-enclosed structure, adjacent to the nucleus. It can be divided into the rough ER and smooth ER
  • The rough ER contains ribosomes, workbenches for making protein. Ribosomes can also be found in the cytoplasm, the watery phase inside cells. For a protein to be made, the DNA sequence for a gene is copied into mRNA (transcription)
  • The ER is also a storage organ for calcium ions (Ca2+).
• endoplasmic reticulum connection to proteins:

  • The mRNA finds the ribosome and is used as a template for making protein (translation).
  • Proteins that reside in the cytoplasm are made by ribosomes in the cytoplasm.
  • Proteins that are destined for insertion in the cell’s membranes or for secretion are made by ribosomes in the rough ER.
• golgi apparatus

  • the golgi extends from the ER. It consists of stacks of membrane.
  • membrane proteins and secreted proteins are modified and sorted in the Golgi to their final destinations in the cell.
• plasma membrane:

  • cells are surrounded by a plasma membrane (cell membrane, neuronal membrane).
  • main job is to form a barrier, separating the watery extracellular space from the watery cytoplasm. It is made of phospholipids.
  • phospholipids have a hydrophilic (water-loving) head group and hydrophobic (water-fearing) tails.
  • arranged in a bilayer, with the head groups facing out towards the water and the hydrophobic tails facing each other.
• mitochondria:

  • the powerhouses of the cell
  • about 20% of the calories you take in are used by the brain. The brain only uses glucose for energy (at least under non-starvation conditions)
• glucose uptake:

  • glucose gets taken up into neurons by special transporter molecules. from there, it goes through a metabolic pathway called “glycolysis.” pyruvate is produced, which goes through the Kreb’s Cycle in the mitochondria, producing water and CO2.
  • glycolysis and particularly the Kreb’s Cycle produce lots of ATP which is used by neurons as an energy source to power all sorts of chemical reactions.
• neuron parts:

  • axon: sends signals throughout the nervous system
  • neurons have dendrites which specialize to receive signals
• the part of the neuron where the cell body meets the axon is called the “axon hillock.” axons also have branches called collaterals.
• cytoskeleton:

  • all cells have a cytoskeleton
  • like poles propping up the plasma membrane
  • neurons have microtubules, made of a protein called “tubuilin.”
  • run parallel down the length of the axon
  • neurons also have microfilaments (made of protein actin) and neurofilaments (made of filamin)
  • all lend structual support to the neurons
• axon terminal / bouton:

  • contains synaptic vesicles (membrane-bound sacks of neurotransmitter) and lots of mitochondria.
  • no ribosomes found here so proteins have to be made then travel to the terminal
• Fast transport:

  • anterograde (from the cell body to the terminal) direction
  • retrograde (from the terminal to the cell body)
  • works at a rate of hundreds of mm a day
  • used for cargo in membrane vesicles (membrane proteins, lipids, neurotransmitters)
• slow transport:

  • few mm per day
  • used for cytoplasmic proteins (enzymes or cytoskeletons)
• Anterograde transport is accomplished by a motor called kinesin, which walks along the microtubules
• Retrograde transport is accomplished by a motor protein called dynein, which also uses microtubules as tracks.
• • dendrites are in charge of receiving signals (found on the post-synaptic side of a synapse)
  • shorter than axons and can be decorated with spines
  • spines can grow/shrink based on strength of synaptic connection
• ways to classify neurons:

  • Connections (sensory, motor, interneuron)
  • Projections
  • Shape
  • Transmitters (-ergic)
  • Electrical properties
  • Gene expression
• myelinating glia:

  • method of increasing  λ
  • myelin: wraps of plasma membrane
  • increases membrane resistance and increases  λ
  • gaps between wraps of myelin are called nodes of ranvier
• astrocytes:

  • most abundant cell type in brain
  • mop up after active neurons (neurotransmitters and excess K+ leftover)
  • also occupy a lot of space between neurons
  • act as a physical barrier to limit neurotransmitter spread outside of the synaptic region
• charge:

  • Physical property of certain particles.
  • Particles can have a positive charge, a negative charge, or no charge (neutral).
  • Like charges repel each other.
  • Opposite charges attract each other.
• ions to know:

  • •sodium (Na+)
  • potassium (K+)
  • calcium (Ca2+)
  • magnesium (Mg2+)
  • chloride (Cl-)
• electric current:

  • movement of charge
  • in neurons, currents are made by ions moving from one side of the plasma membrane to the other
• conductance:

  • Conductance (units of siemens, S) refers to how easy it is for current to flow.
  • The larger the conductance (g) the larger the current (I).
  • The smaller the conductance, the smaller the current.
  • The inverse of conductance (1/g) is resistance (units of ohms, Ω). Resistance is opposition to current flow.
• voltage: a difference in electrical potential between two points
• ohm's law:

  • I = gV (current is equal to conductance times voltage)
  • as g goes up, I goes up
  • as V goes up, I goes up (bigger potential difference driving the charges downhill)
  • Can also rewrite Ohm’s law as: V = IR
• neuronal membrane resting:

  • When we say “rest” or “resting,” what we really mean is not signaling.
  • When we say “active” or “action” we are talking about a neuron in the process of sending an electrical signal.
• • Recall that the brain uses 20% of the body’s energy.
  • Glucose is converted to ATP; ATP powers lots of chemical reactions.
  • The Na+/K+ pump is a protein that consumes a good chunk of the brain’s energy.