S. D. V. Stephens

notes / Basic Neuroscience and Geometry of Neuroscience / chapter 1: Neurons and Signalling

3 Hormones and Neurotransmitters

This lecture has three goals: to understand the steps of synaptic transmission, to describe the main functions of key neurotransmitters, and to critically evaluate outcomes associated with neurotransmitter dysregulation. It opened with a discussion question about myelin, which is collected with the other questions at the end.

Synaptic transmission

The action potential from the last lecture travels down the axon of one neuron, the pre-synaptic (“sending”) cell, to its axon terminals. There the axon terminals meet the dendrites of the next neuron, the post-synaptic (“receiving”) cell.

Definition 3.1 (Synapse). The synapse is the point where an axon terminal of the sending (pre-synaptic) cell meets a dendrite of the receiving (post-synaptic) cell.

Two neurons: an action potential travels along the pre-synaptic (sending) cell's axon to its axon terminals, which meet the dendrites of the post-synaptic (receiving) cell at the synapse.

Steps of synaptic transmission

  1. The neurotransmitter, or the enzymes needed to make it, is made in the cell body.
  2. It is transported down the axon to the axon terminals and stored there in small sacs called vesicles.
  3. The vesicles release the neurotransmitter into the synapse.
  4. The neurotransmitter binds to receptors on the post-synaptic cell, which triggers a response in that cell.
  5. The excess is taken back into the pre-synaptic neuron through transporters in its membrane.

The lecture’s diagram also shows two enzymes that break neurotransmitter down: a degradation enzyme in the synapse itself, and a metabolizing enzyme inside the sending neuron’s terminal.

Close-up of a synapse showing neurotransmitter made in the cell body, stored in vesicles in the axon terminal, released into the synapse, bound by receptors on the receiving neuron, and taken back into the sending neuron by a transporter, with metabolizing and degradation enzymes.

The lecture also shows a photo of an actual synapse, taken with an electron microscope (the scale bar is 0.5 μm). The axon terminal at the top is packed with small round synaptic vesicles. Below it, separated by a thin dark line where the two membranes meet (the synapse), is a dendrite.

What is a neurotransmitter?

Definition 3.2 (Neurotransmitter). A neurotransmitter is a chemical messenger that a neuron stores in vesicles in its axon terminals and releases into the synapse, where it binds to receptors on the receiving cell.

Neurotransmitters and hormones

GABA and glutamate

GABA is inhibitory: it decreases action potentials. When GABA binds to GABA receptors, Cl (chloride) flows into the receiving cell more readily.

Glutamate is excitatory: it increases action potentials. When glutamate binds to glutamate receptors, Na flows into the receiving cell more readily.

Spike trains comparing the inhibitory transmitter GABA, with few action potentials, and the excitatory transmitter glutamate, with many closely spaced action potentials.

Remark. This ties back to the action potential. Na entering the cell is depolarization, which pushes the neuron toward threshold, so glutamate makes the receiving cell fire more. Cl carries a negative charge, so letting it in makes the inside of the cell more negative and moves it away from threshold, so GABA makes the receiving cell fire less.

The lecture shows the chemical structure of each of the next three neurotransmitters. Notice how much dopamine and norepinephrine resemble each other.

Skeletal chemical structures of dopamine, norepinephrine (dopamine with an extra OH group on its side chain) and serotonin (5-hydroxytryptamine).

Dopamine

Dopamine is mainly produced in a region called the ventral tegmental area, and it is processed throughout the limbic system. Dopamine is often described as the brain’s “reward” chemical. The lecture’s more careful description is that dopamine signals motivational salience.

Definition 3.3 (Motivational salience). Motivational salience is the perceived desirability or aversiveness of an outcome: how much something seems worth approaching or avoiding.

Dopamine is also involved in learning and memory, and in motor function.

Serotonin

Serotonin is also known as 5-HT (5-hydroxytryptamine). About 90% of the body’s serotonin is produced in the gastrointestinal tract; the remaining 10% is produced in the brainstem’s raphe nuclei.

Serotonin is involved in:

  • mood
  • anxiety
  • memory formation
  • digestion
  • sleep
  • sexual inhibition

Norepinephrine

Norepinephrine is produced by very few cells, primarily in a small cluster of neurons called the locus coeruleus. Only about one millionth of the neurons in the brain produce it, but those neurons send projections everywhere.

Norepinephrine is involved in physiological arousal and wakefulness, including:

  • the fight-or-flight response
  • stress and anxiety
  • attention

Acetylcholine

The lecturer introduced this one as “a neurotransmitter we’ll probably never talk about again. But it does EVERYTHING”: nearly every function you can think of has acetylcholine involved.

Acetylcholine is highly prevalent in the peripheral nervous system (the nerves outside the brain and spinal cord). It is released at neuromuscular junctions, where nerves meet muscles, to control movement.

It is also produced in several brain regions involved in:

  • learning, memory and attention
  • arousal
  • muscle movement
  • cardiac function and blood pressure

The lecture’s brain diagram shows acetylcholine pathways fanning out from the septal nuclei and the substantia innominata, near the front of the brain, to the cortex, cingulate gyrus, hippocampus and amygdala, and from a cluster in the brainstem up to the thalamus and down the brainstem.

Alzheimer’s disease and dementia have been associated with low acetylcholine levels. Acetylcholine signaling is also the target of many poisons: some natural toxins work by blocking it, while nerve agents work by stopping acetylcholine from being broken down, so that it builds up at the synapse.

Oxytocin

Oxytocin is involved in:

  • pair-bonding
  • affiliation
  • reproduction
  • smooth muscle contraction

Oxytocin is a small peptide: a chain of nine amino acids (the building blocks of proteins), Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH, closed into a ring by a sulfur–sulfur (S–S) bond between its two cysteines (Cys).

Oxytocin as a chain of nine amino acids, Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2, with a sulfur-sulfur bridge joining the two cysteines.

Vasopressin

Vasopressin is involved in:

  • water retention
  • vasoconstriction (narrowing of blood vessels)
  • aggression and dominance
  • pair-bonding and monogamy

The lecture also shows vasopressin’s chemical structure: like oxytocin, it is a short chain of amino acids closed into a ring by a sulfur–sulfur bond.

A video followed, showing three connected cages with a small rodent in each. It appears to be a partner-preference test of the kind used to study pair-bonding.

Testosterone and estrogen

Testosterone and estrogen are not just “male” and “female” hormones! Estrogen is “processed” testosterone: the body makes estrogen from testosterone. Both hormones are involved in the development of the reproductive organs and in reproductive endocrine (hormonal) processes: puberty, spermiogenesis (the final stage of sperm production) and ovulation.

The two hormones share most of their functions:

Testosterone Estrogen
Sexual development Sexual development
Stereotyped male sexual behavior Stereotyped female sexual behavior
Dominance & aggression Dominance & aggression
Stress regulation Stress regulation
Memory Memory
Puberty (voice deepening, male genital development) Puberty (physical growth, muscle development, ova & sperm maturation)

Estrogen is essential for memory

Example 3.4 (Estrogen and memory). Rats with their ovaries removed have impaired memory ability. Supplementing them with synthetic estrogen restores memory and decreases anxiety behavior. (Dr. Emese Renczés is pictured with this work.)

Estrogen deficiencies cause cell death in the hippocampus: when the hippocampus’s estrogen receptors are not activated, its mitochondria (the cell’s energy-producing structures) degenerate. (Dr. Rukmani Pandey is pictured with this work.)

Testosterone is also essential

Example 3.5 (Testosterone and memory). Decreased testosterone impairs memory, while supplementing testosterone increases memory ability. There’s a limit: too much testosterone starts to decrease memory performance again. (Dr. Karlye Rodriguez-Wisdom is pictured with this work.)

This effect is mediated by testosterone maintaining synaptic function in the hippocampus. (Dr. Seppan Prakash is pictured with this work.)

Check yourself

Question 3.6. Describe three symptoms that someone will likely have if their brain is not producing enough myelin, or if the myelin sheath is damaged. Why is myelin important to these functions?

Show solution

From multiple sclerosis (previous lecture): impaired sensation, impaired vision, muscular weakness and impaired coordination. Myelin insulates the axon and speeds up transmission, so without it the signals behind sensing, seeing and moving slow down or fail.

Question 3.7. Why are dopamine-based drugs addictive? What happens if you have a deficiency in dopamine?

Show solution

Dopamine signals motivational salience and supports learning, so a drug that boosts dopamine makes taking it seem highly desirable and teaches the brain to seek it again. A deficiency would show up in what dopamine regulates: motivation, learning and memory, and motor function.

Question 3.8. What happens if you have too little serotonin? Too much?

Show solution

Either one disturbs what serotonin regulates: mood, anxiety, memory formation, digestion, sleep and sexual inhibition. For example, since serotonin promotes sexual inhibition, too much would be expected to lower sex drive.

Question 3.9. How might oxytocin be associated with giving birth?

Show solution

Oxytocin drives smooth muscle contraction and is involved in reproduction, so it can drive the contractions of labor. Its role in pair-bonding and affiliation also fits the bond between parent and newborn.

Question 3.10. What happens if you take a drug that shuts down vasopressin?

Show solution

Vasopressin makes the body retain water, so blocking it means the body holds on to less water and loses more as urine, risking dehydration. It would also be expected to affect behaviors vasopressin supports, such as aggression and pair-bonding.

Question 3.11. Where are neurotransmitters released from, and where do they bind to?

  • a. Soma, axon
  • b. Axon, soma
  • c. Dendrites, axon terminals
  • d. Axon terminals, dendrites
Show solution

d. Axon terminals, dendrites. Neurotransmitter is released from the axon terminals of the sending cell into the synapse and binds to receptors on the dendrites of the receiving cell.

Question 3.12. Which of the following does dopamine regulate?

  • a. Happiness
  • b. Reward
  • c. Pair bonding
  • d. Stress
Show solution

b. Reward, or more precisely motivational salience: how desirable or aversive an outcome seems.

Question 3.13. Which of the following does oxytocin regulate?

  • a. Happiness
  • b. Reward
  • c. Pair bonding
  • d. Stress
Show solution

c. Pair bonding.

Question 3.14. Which of the following does norepinephrine regulate?

  • a. Happiness
  • b. Reward
  • c. Pair bonding
  • d. Stress
Show solution

d. Stress. Norepinephrine drives physiological arousal, including the fight-or-flight response and stress and anxiety.

Question 3.15. You’re an endocrinologist who treats patients with low levels of estrogen. What symptoms would you likely see in your patients?

  • a. Decreased sex drive
  • b. Memory impairments
  • c. Shorter height
  • d. All of the above
  • e. A & B only
Show solution

d. All of the above, going by this lecture: estrogen supports sexual behavior and memory, and drives physical growth at puberty. So low estrogen can show up as decreased sex drive, memory impairments and, when it happens during puberty, reduced growth.

Question 3.16. Many people will have the misfortune of getting hangovers at some point in their life, and vasopressin is a big part of why. Based on what you’ve learned, how is vasopressin implicated in how we get hangovers? (Hint: alcohol inhibits vasopressin.)

Show solution

Vasopressin makes the body retain water. Alcohol inhibits vasopressin, so after drinking the body loses more water than usual and becomes dehydrated, which is a big part of a hangover.