BioPsych

Don’t let the silly mnemonic fool you.  These gaps between neurons are important. Everything you do, think or feel depends on neurotransmitters making it across synapses. Diseases, drugs and chemicals that stop synaptic function, stop your muscles from working, your heart from beating, and your brain from living.

A lot can happen between neurons. These separations are called synapses. Structurally, synapses are intercellular spaces (between cells). They are small separations between neurons.

Synapses can be electrical or chemical. They are the location where drugs and chemicals impact behavior. Pay particular attention to how chemical bonds are formed and how synapses are cleaned up.

Notes

• Typical Electrical Neuron & Chemical Synapse
• At Neuron Terminal
  • Depolarization causes calcium gates open
  • Calcium flows into terminal
  • NT is released
    • within 1-2 milliseconds
• Sherrington
  • Reflex Arc
• Synapse
  • Thousands of synapses along neuron
  • Three types
    • 1. Axon-Soma (axosomatic)
      • Usually inhibitory
    • 2. Axon-Axon
      • Electrical
    • 3. Axon-Dendrite
      • Dendrites
      • Chemical
  • 40 nanometers
    • Sheet of paper 100,000 nm
    • Hair 40,000 nm
    • Red blood cell 7,000 nm
    • Bacteria 5,000 nm
    • Virus 30-50 nm
    • Ultraviolet light 40 nm
    • Synapses 40 nm
    • Cell membrane 10 nm
    • DNA 2.5 nm
•  Fill the gap with chemicals
  • 4 Stages
  • 1. Release the chemical
    • Pre-synapse
  • 2. Float across synapse
    • Diffusion
  • 3. Bind with receptor
    • Not just anyone
    • Matching key
      • Nicotinic receptors
        • Activated by nicotine
        • Blocked by curare
  • 4. Clean up the gap
    • Destroy leftovers
    • Recycle (reuptake)
• Release and Diffusion
  • Release of NT thru membrane
    • Exocytosis
      • Lasts 1-2 ms
      • No more than 0.01 ms across a 20 to 30 nanometers wide cleft
    • Opposite of endocytosis
      • Cells absorb protein molecules
    • Only release 2-3 transmitters
      • always the same combo
• Ionotropic effects
  • used for quick events
    • visual stimulation
    • muscle movements
  • quick start (10 ms)
  • short duration (30 ms)
  • localized effect on membrane
  • opens gates for ions
    • e.g.,acetylcholine
  • Most common
    • glutamate (excitatory)
    • GABA (inhibitory)
• Metabotropic effects
  • Slow start (30 m)
  • Can last for hours
  • Has broad impact
  • Can affect most of a cell
    • opens or closes ion channels
    • changes protein production
    • activates chromosomes in cell
  • Activates G-protein inside membrane
  • G-protein activates 2nd messenger system
• G-proteins
  • Little protein that sits close to receptor
    • coupled to energy-storing molecule GTP (guanosine triphosphate)
  • Changing cell causes the G-protein to change shape
  • Part of G breaks off to bind to a site on an ion channel
  • Binding causes ion channel to open
  • G-proteins can also activate enzymes
  • Enzymes causes production of second messenger
  • Second messenger binds to ion channels to open them up
• After causing action potential, after exciting or inhibiting
  • Inactivation
    • broken down by an enzyme
    • acetylcholine is broken down by Acetylcholinesterase
  • Reuptake
    • detach from the receptor
    • taken back by presynaptic cell
    • Transporters
    • Serotonin is reuptaken
• Characteristics
  • Summation
    • also called integration
    • neuron can receive input from 1000+ cells
    • each input either excites or inhibits
    • interaction between incoming EPSP’s (excitation) and IPSP’s (inhibition)
  • 1. Temporal summation
  • 2. Spatial
• Neurotransmitters
  • Brain uses dozens of NTs
  • No single neuron releases all
  • A neuron may respond to different NTs at different synapses
  • 300+ types
• 6 Major Types of NTs
  • 1. Amino acids
    • Building blocks
    • Essential (must get from food)
    • Unessential (can synthesize)
  • 2. Monoamines
    • Based on amino acids
    • Histamine
    • Catecholamines (dop, nor, ep)
    • Tryptamines (serotonin-melatonin)
    • Trace amines
  • 3. Neuropeptides
    • Chains of amino acids
    • Neuropeptides = small chains
    • Poloypeptides = long chains
    • Proteins = very long chains
  • 4. Acetylcholine
    • Individual neurotransmitter
    • First NT discovered
  • 5. Purines
    • Not stored in vesicles
    • Adenosine and derivatives
    • ATP (adenosine triphosphate)
    • Synthesized in mitochondria
    • Easily combines to make reactions
    • Present in cytoplasm of every cell
    • High-energy molecule; stores energy
  • 6. Gases
    • Nitric oxide (NO)
    • possibly others
• Most Common In Brain
  • Glutamate 90%
  • GABA 9%
  • Other 1%
• Glutamate
  • Amino acid
    • Building blocks of proteins
  • MSG (monosodium glutamate)
  • Non-essential (body can create)
  • Glutamine
  • Serine
  • Taurine
  • Glutamate to Glutamine
  • Glutamate & Amonia
  • Glutamine Synthetase enzyme
  • 90% of glutamine synthesized in muscles
  • Small amounts also released by lungs and brain
  • Liver could synthesize glutamine but doesn’t, regulates it
  • Collect glutamine from the gut
• Glutamate-Glutamine Cycle
  • Neurons & glial cells work together to maintain glutamate supply
  • Glial cells release glutamine
    • Astrocytes
  • Sent to presynaptic terminals
  • In neuron terminal
    • Converts glutamine to glutamate
    • by glutaminase (enzyme)
  • Sent to vesicles
  • Packaged in vesicles by VGULT transporter
  • Released & Binds
  • Reuptaken by EAAT
    • Excitatory amino acid transporter
  • 5 types (1 for each receptor type)
  • Reuptaken by glial cells
    • converted into glutamine
    • By glutamine sythetase
  • Transported out of cells into neuron terminal
• At GABAergic synapses
  • called GABA-glutamine cycle
  • Glutamine converts to glutamate
  • Glutamate into GABA
  • By glutamate decarboxylase
  • Upon release, GABA is taken up by glial cells
  • GABA transporters
  • Glial cells
  • Convert GABA into succinate
  • Series of steps to alpha-ketoglutarate and then back to glutamine
• Glutamate
  • Easily binds
  • Excitatory effect
  • Important for:
    • neural communication
    • memory formation
    • learning
    • regulation
  • Used in:
    • 50% of body’s synapses; 90% of brain’s synapses
  • Problems
    • Too much in MS
    • Binds too easily in epilepsy
    • Not enough in schizophrenia
    • MIGHT cause:
      • Ischemia
      • Thinning of blood vessels
      • Restricted blood supply
      • Thrombosis, vasoconstriction
  • Types of Receptors
    • Ionotropic receptors (iGluRs)
      • NMDA 4 subtypes
      • Kainate 5 subtypes
      • AMPA 7 subtypes
    • Metabotropic receptors (mGluRs)
      • 8 subtypes
      • Cascade of reactions
      • G protein
  • Used as a point-to-point transmitter
  • Used as a spill-over transmitter
  • Synaptic crosstalk
    • summation of glutamate from neighboring synapse causes extrasynaptic signaling
  • Glutamate transporter
    • Neurons & glial cells
    • Rapidly remove glutamate from extracellular space
    • Glutamate transporter problem
      • In brain injury or disease
      • Can work in reverse, builds up excess glutamate outside cells
    • Reversed transporter
      • Causes calcium ions to enter cells
      • Go thru NMDA channels
      • Results can be:
        • Neural damage & cell death; called excitotoxicity
        • Damage to mitocondira
          • (high intracellular calcium)
        • Might explain:
          • Stroke
          • ALS
          • Autism
          • Alzheimer’s
        • Implicated in epileptic seizures
        • Spontaneous opening of voltage-gated calcium channels?
  • Glutamate levels
    • Controlled by ATP
    • controls glutamate transport levels
• GABA
  • From Glutamate
  • 9% of brain
  • Inhibitory
  • Regulates muscle tone
  • Impacts opening of
    • Negative chloride ions in
    • Positive potassium ions out
  • Types
    • GABAa = ionotrophic
    • GABAb = metabotropic
      • G-protein
  • Low GABA
    • Epilepsy?
  • High GABA ($ receptors)
    • Benzodiazepine
    • Barbiturates
    • Alcohol

Ggg

Neurons are a lot like toilets.

People use them but don’t talk about them. They are usually hidden from view. And you have to wait for them to refill.

After a flush, it can take 3 or 4 minutes until the apparatus is ready for regular use. Neurons are a lot faster but the process is similar. It only takes a neuron 3ms to recover, as it resets its ion channels and finds its resting potential.

Neurons are like living batteries that automatically recharge. It’s a complicated and fascinating process.

Ggg

Notes

• Neurons are electrical
  • Communication within a neuron
  • Membrane potential
    • inside vs. outside
•  Two Basic Principles
  • 1. Resting Potential
  • 2. Action Potential
• 1. Resting Potential
  • Semi-Permeable Membrane
    • Positive ions outside
    • Negative inside
    • – 70 mvolts
    • Chloride stuck inside (negative)
  • Ion gates are specific
    • Sodium gates
    • Potassium gates
    • Calcium gates
  • Flow for 2 reasons
    • 1. Passive Transport
      • From more to less concentrated
      • Passive transport (no energy)
    • 2. Active Transport
      • Primary active transport
      • Use chemical like ATP
      • Use fuel = glucose
      • Sodium Pump
        • Secondary active transport
        • Use electrochemical gradient
  • How does it work?
    • NT activates dendrite receptors
    • NT opens lipid gate
    • Intracellular charge more positive
    • More NT
    • Higher internal positive charge
    • No major change until -55
  • Hit Threshold of -55
    • Voltage gates open
    • 2 kinds: Sodium & potassium
• 2. Action Potential
  • Sodium voltage gates open
  • Sodium rushes in
  • Only about 1% of available
  • Impacts voltage for next gate
  •  If sodium gates don’t open… neuron doesn’t fire!
    • Local anesthetics block gates
    • Novocain, Xylocaine, etc.
• Down the axon
  • Sodium gates open
    • • Sodium rushes in
    • • Impacts voltage for next gate
  • Sodium gates wide open
    • Cell is already positive
    • Potassium rushes OUT
• 1-WAY ONLY
  • Sodium gates close quickly
  • Can’t reopen (too positive in cell)
• How Membranes Work
  • Primarily composed of lipids
    • Other molecules move from high concentration to low across it
    • Diffusion
  • Selectively Permeable
    • Some go through easily
      • Water, oxygen, carbon dioxide
    • Some go through slowly
      • Potassium
      • Its gates are slightly open
    • Some don’t go through at all
      • Sodium channels are closed
      • Chloride can’t get out
• Electrolyte = Water solution
  • adds or removes electrons
  • ionizes a soluble acid, base or salt
• Ion = charged molecule
  • positively charged
  • negatively charged
• Electrostatic pressure
  • charged atomic particles
  • opposite signs attract
  • same sign repulsive
• Ion channels
  • Specialized protein molecule
  • Lets specific ions enter or leave
• Why open?
  • Chemical
  • Voltage
• Sodium-potassium transporter
  • protein in all cell membranes
  • extrudes sodium ions (pushes)
  • sodium pump
    • 2 in , 3 out
• Conduction
  • 1. Cable conduction
    • Passive conduction
    • Decreases as goes down length of axon
    • Less as you go
  • 2. Saltatory conduction
    • Node to node
      • in myelinated axons
      • increases the speed of impulse; 10x faster
    • No sodium channels under sheath
      • breaks in sheath every 1mm
      • have sodium channels
      • un-mylinated sections
    • nodes of Ranvier
• BOTH Cables & Node work together
  • Cable conduction
  • Node to node
• Action Potential
  • the nerve impulse
  • +50 millivolts
  • 200 mph
• Negative After-Potential
  • More negative than resting potential
  • Reaches resting potential by diffusion
  • Sodium-potassium pump
• Principles
  • All-or-None Law
    • Either neuron fires or it does not
    • It fires if it passes a certain threshold
    • If it fires, it does so at full strength
    • Can’t change intensity
    • Can’t go fast or slow
  • Firing rate = frequency
  • Refractory Period
    • Can’t fire until it recovers
    • 3 millisecond to totally “reload”
      • Refill (toilet tank level)
    • 2 part recovery process
    • Absolute Recovery Period
      • Not recovered
      • Can’t fire for 1 ms
    • Relative Recovery Period
      • Fire if lots of $
      • Resting potential 2 ms later
• Thresholds
  • Super-threshold stimulus
  • 1 neuron releases enough NT
  • activates (depolarize) the post-synaptic neuron in 1 shot
• Summation
  • Not enough NT to trigger firing
  • 1. Temporal Summation
    • 1 neuron, several times
    • So NT doesn’t dissipate
  • 2. Spatial Summation
    • Many neurons, 1 time
• 1 cell can code 2+ percept. experiences
  • 1 Cell: 2 codings
  • excitation signals one quality
  • inhibition signals another
    • Fire = yes Not fire = no
    • Fire = left Not fire = right
    • Fire = blue Not fire = yellow

Why do my neurons look like food?

At the most basic level, the body is run by neurons. These cells link together to provide sensory information and trigger muscle movements.

Each neuron is a cell with all the regular functions. It’s cell body (soma) has a nucleus, DNA, RNA, mitochondria and all the standard cell components.

Neurons have some additional structure components and a very different functional component. Structurally, neurons typically come with extensions. The dendrites look like ginger covered with spiny bristles. Neurotransmitters bind to the receptors of the dendritic spines, so dendrites are important for inputs.

Neurons are amazing. Functionally, they are living batteries that discharge quickly, recharge and discharge again. There are factories to produce the needed components, tubes to carry products, and pumps and gates to manage its climate.

Pay particular attention to how neurons are formed and how they are aided by glia.

Notes

• Neurons
  • Receive & transmit to other cells
  • Many last your whole life
  • Other cells die and are replaced
  • Most aren’t replaced
    • Hippocampus neurons CAN re-grow
    • In General
  • have less neurons as get older
• Neuron Development
  • Create twice as many as need
  • Winnowing
    • just before and after birth
  • 50,000 cells each second
    • for most of intrauterine life
• Soma
  • maintains cell life
  • contains nucleus
  • support structures
  • only one per neuron
  • cell body
  • Looks spotty
    • (Nissl substance)
      • Chromophil granules
      • In soma & dendrites
      • Not in axons
      • Synthesize proteins & regulate metabolism
• Dendrites
  • Thicker than axon
  • Look like tree roots or ginger
  • Attached to the soma
  • Receives info from other neurons
  • Control which gates open
  • Control how quickly gates open
  • Control how long stay open
  • Control rate thru gate
• Dendritic Spines
  • Spiny outgrowths
  • Adults have fewer, children more
  • Synapse plasticity
    • Involved how?
    • Not in most brain neurons
  • Types
    • Stubby
    • Mushroom
    • Thin
      • Usually: spine head with long skinny neck
• Ribosomes
  • Rough texture
  • An organelle
    • specialized function
  • Protein factory for local use
• Axon Hillock
  • In larger neurons
  • Expanded region at initial end of axon
  • Connects cell body to the axon
  • Site of summation
  • Collection of incoming information
  • Electric charge adds up
  • More than threshold causes discharge (action potential)
• Axon
  • Vary in length
    • .1 mm to 1 meter
    • Longer than dendrite
  • Vary in width
    • Thin; about 1 micrometer
    • Thinner than dendrite
  • Can branch at end
  • Usually only 1
  • Output
    • Branch at end (not near cell)
  • Smooth surface
    • No ribosomones
  • Can have myelin
    • Myelin
    • Insulation
    • Fatty layers that coats some axons
• Myelin sheath
  • wraps axon
  • type of glial cell
  • Prevents activation of adjacent axons
  • 14th week of fetal development
  • Two Types
    • 1. In Brain & Spinal Cord: Oligodendrocyte
      • 80% lipid
      • 20% protein
      • Can cover 50 axons
    • 2. Peripheral System: Schwann Cells
      • myelinating & nonmyelinating
      • 1 axon only
      • Help keep neurons alive
      • Insulate 100 micrometres of axon
        • Each cell 100 micrometers long
        • 10k per meter
      • Regularly spaced
      • Gaps = Nodes of Ranvier
      • Schwann Cells
        • Spiral around axon
        • 100+ revolutions
        • Looks like log or rolled-up paper
        • Inner layers are myelin
        • Mostly lipid
        • Outer layers = neurolemma
        • Plasma membrane
      • Saltatory Conduction
        • Slows down as distance increases
        • Repropagation
        • Node to node
          • 10x faster
        • Exposes neuron to extracell. fluid & ion flow
          • “naked” section of myelinated axon
• Axon Terminals
  • Branches at end of axons
  • Presynaptic
• Terminal Buttons
  • Secrete neurotransmitter
• Organelles = specialty units
  • Mitochondrion
    • Cellular power plants
    • Generate ATP
    • Power chemical changes
  • Nucleus
    • contains chromosomes
    • covered by membrane
  • Nissl Bodies
    • groups of ribosomes
    • protein synthesis
  • Endoplasmic reticulum (ER)
    • system of tubes
    • transport materials within cytoplasm
    • rough (ribosomes)
    • smooth (no ribosomes)
  • Golgi Apparatus
    • Stuff peptides & proteins into vesicles (sack-like cavities)
  • Microfilaments/Neurotubules
    • transport system within a neuron
    • also used for structural support
• Types of Neurons
  • Location
    • Peripheral nervous system
      • Sensory neuron
        • detects changes in world
        • detects internal changes
        • sends info to CNS
          • Central nervous system
      • Motor neuron
        • controls contraction of a muscle
        • controls secretion of a gland
        • Interneuron = connects other neurons
  • Number of Extensions
    • Bipolar
      • 1 dendrite, 1 axon
      • Retina and smell
      • 2 processes (extensions)
    • Pseudounipolar
      • Biploar who lose 1 process
      • No dedrites
      • Becoming a unipolar neuron
    • Unipolar
      • Sensory Neuron
    • Multipolar
      • 99% of neurons
      • many processes (extensions)
      • only one axon
      • Spinal motor neurons
    • Pyramidal neurons
      • Purkinje cells
      • can have over 1000 dendrites
      • connect to 10-20k cells
      • some of largest neurons in brain
      • stacked one in front of the other
      • look like dominos
  • Direction They Send Info
    • Sensory neurons (afferent)
      • from sensory receptors
      • skin, eyes, nose, tongue, ears
      • to central nervous system
    • Motor neurons (efferent)
      • from central nervous system
      • to muscles or glands
      • get info from interneurons
      • directly from sensory neurons
      • in some reflexes
    • Interneurons
      • Between sensory & motor neurons
      • No other neurons around them
      • Don’t need dendrites to receive input
      • Connect to each other
      • Intrinsic, association, relay, or local circuit (local) neuron
• Glial Cells
  • Supporting cells
    • called neuroglia or “neural glue”
    • supporting cells of CNS
  • 6 Types of Glial Cells
  • 1. radial glial
    • Help generate neurons & astrocytes
    • Cables neurons use to find home
  • 2. astrocytes
    • Surround synapses
    • Provide nutrients & raw material
    • Limit neurotransmitters
    • Engulf dead cells & form scar tissue = phagocytosis
    • Regulate chemical composition of extracellular fluid
    • Star cells
    • Help neurons:
      • 1) transport nutrients to neurons
      • 2) regulates extracellular space
      • 3) digest parts of dead neurons
      • 4) clean up brain “debris“
      • 5) hold neurons in place
  • 3. oligodendrocytes
    • produce mylein sheath in CNS
  • 4. Schwann cells
    • produce myelin sheath in PNS
  • 5. microglia
    • smallest glial cells
    • act as if they were phagocytes
      • (Bacterial eating white blood cells)
    • protect brain from invading microorganisms
  • 6. satellite cells
    • physical support to PNS neurons

ffg