[Last updated:]

Feb. 23, 2021


PSY 340 Brain and Behavior

Class 08: Chemical Events at the Synapse


Some thought questions:
To answer these questions, we must understand the chemical events at the synapse & what happens with the neurotransmitters secreted there.

          Activity at the SynapseChemical Activity at the Synapse: Summary

Note: the numbers in the explanation on the left correspond to the numbers in the diagram on the right
(1) Synaptic vesicles and peptide neurotransmitters are synthesized in the soma. Vesicles are small spheres which are filled with neurotransmitter molecules (Think: a balloon blown up with water)
(2) These are transported down the interior of the axon to the presynaptic terminal.
(3) Vesicles are stored and smaller neurotransmitters are synthesized in the presynaptic terminal (which is also called the synaptic bouton [or synaptic button)].

(4) Action potentials travel down the axon and cause channels to open in the presynaptic terminal. Calcium ions (Ca++) trigger the release of neurotransmitters at the presynaptic terminal membrane. This release is called exocytosis ("exo" = out of; "cyto" = cell)

We now know that many neurons release more than one type of neurotransmitter, e.g., 2 types at the same time or one type quickly and another type slowly

(5) The molecules of neurotransmitter diffuse across the synaptic cleft (gap) to the postsynaptic membrane almost instantaneously. The molecules remain in the cleft for about 1-2 milliseconds.

(6) Neurotransmitter molecules attach to receptor sites on the post-synaptic membrane and cause post-synaptic activity (discussed below),

(7) Some neurotransmitter molecules may drift away from the cleft. Some will be destroyed in the cleft by enzymes. Others will be taken back up into the presynaptic terminal by transporter proteins (or "reptake" channels); this process is called reuptake.

(8) Back inside the presynaptic terminal, the neurotransmitter molecules may be broken up by the enzyme monoamine oxidase (MAO) or be repackaged into new vesicles.

The microphotograph below shows clustered synaptic vesicles on the right of the presynaptic neuron's axon (ax), the synaptic cleft, and the postsynaptic neuron's dendrite (d). All along the presynaptic neuron membrane, the image captures synaptic vesicles merging with the membrane in the process of exocytosis. It appears online in Ackerman, Gregory, & Brodin (2012).


The May 30, 2014 issue of the journal Science offers the most detailed look at the synaptic bouton (that is, the presynaptic terminal button) ever created. It involves 300,000 individual proteins compressed into a space of just 0.37 ± 0.03 cubic micrometers. Here is what a slice of that 3-dimensional image looks like:


A. Types of Neurotransmitters

Some Important (but not all) Functions & Facts
Amino Acids  Glutamate (Glu) • Most widely-employed excitatory neurotransmitter in the CNS; role in long-term memory
  GABA (Gamma-aminobutyric acid) • Most widely-employed inhibitory neurotransmitter int he CNS; inhibits post-synaptic neurons by hyperpolarizing them (via Cl- and K+ gates) which makes them less likely to fire.

• Effects are enhanced/increased by alcohol, sedatives, etc.
Modified Amino Acid Acetylcholine (ACh) • Skeletal motor neurons in PNS (peripheral nervous system)
• Brain: short-term memory
 Monoamines Indoleamine  • derived from tryptophan (an amino acid from diet). The levels of tryptophan determine the levels of serotonin.  Melatonin which affects the sleep-wake cycle and we will study later is also an indoleamine.

 Serotonin (5-HT or 5-hydroxytryptamine) • modulation of emotion (low levels associated with self-destructive behaviors)
  Catecholamines • derived from phenylalanine (an amino acid from diet) -> Tyrosine -> Dopa -> DA/NE/Epinephrine (see below) 

 Dopamine (DA) • promotes coordinated muscle movement (loss = Parkinson's)
• central to experience of reinforcement (e.g., pleasure & enjoyment)
• Newer concept (not in book): tells us what we need to pay attention to: grabs our attention. Makes an experience highly "salient" or urgent.

 Norepinephrine (NE) • modulation of emotion (low levels associated with depression)
   Epinephrine (Adrenaline) • Stimulates sympathetic nervous system
Other Peptides
(ca. 40 different types) 

Endorphins (& enkephalins) • suppresses transmission of pain by hyperpolarizing neurons which send out Substance P [see below]. Similar to effects of opioids (morphine, heroin, etc.)
Substance P • dull chronic pain due to nervous tissue damage or cancer ("c-fiber" pain)
Neuropeptide Y • in hypothalamus, stimulates feeding & fat storage
Purines  Adenosine, ATP,
et al.
• Adenosine: There are adenosine receptors in the basal forebrain cells which send signals to lead us toward sleep. Caffeine blocks these receptors and causes us to stay alert.
• ATP: basic energy molecule in all cells
Gases  NO (Nitric Oxide)  • dilates blood vessels & increases blood flow in brain and male sexual organ (Viagra®, Levitra®, & Cialis® affect NO functioning)

• NOT stored in vesicles, but released as needed.

• This is NOT Nitrous Oxide (N2O) which is the anesthetic "laughing gas".

Sources: Kalat (2005, 2007, 2009. 2016), Kimball (2005)

B. Transport & Storage of Neurotransmitter/Release and Diffusion of Neurotransmitters

              effectsC. Receptor Activation on the Postsynaptic Cell

What happens when neurotransmitters attach to the receptors on the postsynaptic membrane?

1. Ionotropic

2. Metabotropic & Second Messenger Systems

When neurotransmitters attach to receptor, this causes a series of metabolic reactions. These reactions take a while, e.g, beginning 30 mSec or more after the release of the neurotransmitter and lasting for seconds and, even, longer:

Kalat uses a metaphor which I'll borrow. Second messengers are like someone who can't get into a room, but can extend a long stick into the room. Using that stick the person releases an angry dog from a cage and that dog then runs around the room which is filled with all sorts of other animals to attack them. The dog's behavior in attacking these animals causes them to behave in a lot of different ways (e.g., to hide under or climb on top of other furniture, to defecate or urinate out of fright, etc.). Similarly, in second messenger systems, the neurotransmitter (or hormone as we will see later) never gets past the cell membrane itself, but causes something to happen inside the membrane which then affects the cell.

Second messengers can cause multiple changes inside the postsynaptic neuron, e.g., Neuropeptides (endorphins, substance P, neuropeptide Y, etc.) = neuromodulators

Variations in Receptors

Drugs Binding to Receptors

D. Inactivation and Reuptake of Neurotransmitters

E. Negative Feedback from Postsynaptic Cell

[Electrical Synapse model]
F. Electrical Synapse (Gap Junction)

G. Hormones

            Glands      Hypopituitary System
    Pituitary Gland and the Hypothalamus

This page was first posted January 18, 2005.


Ackerman, F., Gregory, J. A., & Brodin, L. (2012). Key events in synaptic vesicle endocytosis. In B. Ceresa (Ed.), Biochemistry, genetics, and molecular biology. doi: 10.5772/45785 Published: July 6, 2012 under CC BY 3.0 license. © The Author(s).

Kimball, J. W. (2005). Synapse. Kimball's biology pages [Online]. Retrieved February 1, 2005 from the Web site: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Synapses.html