Synapses

Synapses can be grouped into different categories, depending on what we’re comparing:

  • Fast vs. Slow
  • Strong vs. Weak
  • Electrical vs. Chemical
    • Electrical are faster, bidirectional.
    • Chemical are more common, slower, more diverse and unidirectional.
  • Excitatory vs. Inhibitory
    • Excitatory (EPSPs) increase the activity of the postsynaptic neuron.
      • Fast EPSPs are usually mediated by $\ce{Na+}$ ionotropic channels.
    • Inhibitory (IPSPs): decrease the activity of the postsynaptic neuron.
      • Usually mediated by $\ce{Cl-}$ ionotropic channels.
      • Can open $\ce{Cl-}$ channels
      • Can open $\ce{K+}$ channels
      • Can block $\ce{Ca^2+}$ channels
      • Common neurotransmitters:
        • Glycine in the spinal cord.
        • GABA in the mammalian brain.

Electrical Synapses

Chemical Synapse

  1. An action potential travels down the axon, arriving at the presynaptic terminal.
  2. The $\ce{Ca^2+}$ voltage-gated channels are opened, leading to an influx of $\ce{Ca^2+}$.
  3. When depolarized, synaptic vesicles are fused with the presynaptic membrane resulting on the release of neurotransmitters or neural modulators into the synaptic cleft.
    1. This fusion happens by the action of the SNARE protein complex, generating a synaptic potential.
    2. The synaptic vesicles are high in synaptobrevin.
    3. The neurotransmitters are released presynaptically in quantized amounts because they’re released in discrete amounts by vesicles.
  4. Then, these molecules are passed through diffusion and connect to the receptors on the postsynaptic membrane.
    1. Receptors are usually made to bind certain specific molecules, allowing for greater customization and variety than electrical synapses.
  5. Neurotransmitters may activate channels in the postsynaptic membrane leading to the generation of a postsynaptic potential.
  6. After being released, 5 different things can happen to a neurotransmitter
    1. Travel across the synaptic cleft and bind to a dedicated receptor.
      1. To avoid leaving the neurotransmitter hanging there for too long:
        1. The receptor acn be resorbed into the postsynaptic cell
        2. Neurotransmitters can be broken down by enzymes
        3. Neurotransmitters can be taken up by certain transport proteins.
        4. Combinations of the previous mechanisms.
      2. These parts can be recycled.

Neuromodulation

The efficacy of a synapse can be changed by a neuronal modulator. They make a synapse with either a pre or post synaptic membrane.

  • Can act in large areas of the nervous system all at once.
  • Can act through:
    • More commonly via GPCRs
    • Voltage-gated ion channels.
  • Can be presynaptically or postsynaptically or both.

Neuropeptides are proteins and are larger than classical neuromodulators. Act exclusively through GPCRs.

  • Pain perception is modulated by opioids.

  • Serotonin system
  • Dopamine: neuromodulator; produced in the brain; mesocortical, mesolimbic, nigrostriatal and tuberoinfundibular pathways;
    • Substantia nigra regulate movement, lost in Parkinson’s Disease
    • L-DOPA can help producing dopamine, gradually becomes less and less effective
    • Reward behaviors, reinforcement learning, regulating movement
  • Cholinergic system
    • Acetycholine
    • Muscle, motor control, arousal and short term memoryx

Facts

  • GABA is the major neurotransmitter for inhibition in the brain.
  • GABA ad Glycine are inhibitors.
  • Acetylcholine is broken down by acetylcholinesterase, a specific enzyme located in the synaptic cleft.
  • Vesicles are recycled.
  • Vesicles fusion:
    • The axon at the presynaptic terminal depolarizes.
    • Voltage-dependent calcium channels open.
    • Calcium concentration inside the presynaptic terminal increases.
    • v-SNAREs and t-SNAREs are brought together by proteins.
    • The vesicular and synaptic membranes fuse together.
  • t-SNARE are found on the membrane of the presynaptic terminal.
  • v-SNARE are found on the vesicle.
  • SNAP-25 is a t-SNARE. Therefore, its cleavage by botulinum toxin impairs synaptic release. However, none of the other processes (acetylcholine synthesis, vesicle loading, changes in calcium concentration) would be affected.
  • End Plate Potentials EPP
  • Synaptic cleft has ~20-40 nanometers wide
  • Neurotransmitter v~0.05 miles x hour
  • Shunting: charged chlorine influx counterbalances the positively charged sodium influx of excitatory synapses. Canceling out.
  • Temporal summation: two EPSPs simultaneously make a bigger EPSP although the amplitude is not the same as summing both amplitude.