5 Notes: Synapses – biologicalpsych.com

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

Leave a Reply Cancel reply