Neurochemistry II

2025-10-07

Rick Gilmore

Department of Psychology

Prelude

– Netflix (2025)

Today’s topics

• Wrap-up on synapses
• Neurotransmitters

Warm-up

What ion flows into the presynaptic terminal and triggers neurotransmitter release when the action potential arrives?

• A. potassium, \(K^+\)
• B. organic anions, \(A^-\)
• C. calcium, \(Ca^{++}\)
• D. chloride, \(Cl^-\)

What ion flows into the presynaptic terminal and triggers neurotransmitter release when the action potential arrives?

• A. potassium, \(K^+\)
• B. organic anions, \(A^-\)
• C. calcium, \(Ca^{++}\)
• D. chloride, \(Cl^-\)

What ion flows into the presynaptic terminal and triggers neurotransmitter release when the action potential arrives?

• A. potassium, \(K^+\) flows out not in
• B. organic anions, \(A^-\) doesn’t flow in or out
• C. calcium, \(Ca^{++}\)
• D. chloride, \(Cl^-\) flows in, but doesn’t trigger NT release

What ways are neurotransmitters inactivated after they bind with a postsynaptic receptor?

• A. Buffering (e.g., by astrocytes)
• B. Chemical breakdown (enzymatic degradation)
• C. Reuptake (into presynaptic terminal)
• D. All of the above

What ways are neurotransmitters inactivated after they bind with a postsynaptic receptor?

• A. Buffering (e.g., by astrocytes)
• B. Chemical breakdown (enzymatic degradation)
• C. Reuptake (into presynaptic terminal)
• D. All of the above

What sort of PSP would opening a Na+ channel produce?

• Na+ flows in, so Excitatory PSP (EPSP)
• Na+ flows out, so Excitatory PSP (EPSP)
• Na+ flows in, so Inhibitory PSP (IPSP)
• Na+ flows out, so Inhibitory PSP (IPSP)

What sort of PSP would opening a Na+ channel produce?

• Na+ flows in, so Excitatory PSP (EPSP)
• Na+ flows out, so Excitatory PSP (EPSP)
• Na+ flows in, so Inhibitory PSP (IPSP)
• Na+ flows out, so Inhibitory PSP (IPSP)

Why must NTs be inactivated?

• Or what would happen if they weren’t?
• Or weren’t quickly?

• Concentration gradient wouldn’t be large
• NT flow would be altered

Synapses

Types of synapses

• Axodendritic (axon to dendrite)
• Axosomatic (axon to soma)
• Axoaxonic (axon to axon)
• Axosecretory (axon to bloodstream)

Wikipedia

General synapse properties

• on dendrites
  • usually excitatory
• on cell bodies
  • usually inhibitory
• on axons
  • usually modulatory (change p(fire))

Encyclopedia Britannica

Neurotransmitters

What are they?

• Chemicals produced by neurons
• Released by neurons
• Bound by neurons and other cells

https://www.compoundchem.com/2015/07/30/neurotransmitters/

What are they?

• Send messages (have physiological effect on target cells)
• Inactivated after release

https://www.compoundchem.com/2015/07/30/neurotransmitters/

Amino acids

Family	Neurotansmitter
Amino acids	Glutamate (Glu)
	Gamma aminobutyric acid (GABA)
	Glycine
	Aspartate

Amino acids

Family	Neurotansmitter
Amino acids	Glutamate (Glu)
	Gamma aminobutyric acid (GABA)
	Glycine
	Aspartate

Glutamate

• Primary excitatory NT in CNS (~ 1/2 all synapses)
• Role in learning (via NMDA receptor)
• Transporters on neurons and glia (astrocytes and oligodendrocytes)
• Linked to umami (savory) taste sensation, think monosodium glutamate (MSG)
• Dysregulation in schizophrenia McCutcheon, Krystal, & Howes (2020), mood disorders (Małgorzata, Paweł, Iwona, Brzostek, & Andrzej, 2020)

Glutamate

Type	Receptor	Esp Permeable to
Ionotropic	AMPA	Na+, K+
	Kainate
	NMDA	Ca++
Metabotropic	mGlu

\(\gamma\)-aminobutyric Acid (GABA)

• Primary inhibitory NT in CNS
• Binding sites for benzodiazepines (e.g., Valium), barbiturates, ethanol, etc.
• Synthesized from glutamate
• Inactivated by transporters

GABA

Type	Receptor	Esp Permeable to
Ionotropic	GABA-A	Cl-
Metabotropic	GABA-B	K+

What PSP will occur if we open a K+ channel?

• K+ flows out, so excitatory (EPSP)
• K+ flows out, so inhibitory (IPSP)

What PSP will occur if we open a K+ channel?

• K+ flows out, so excitatory (EPSP)
• K+ flows out, so inhibitory (IPSP)

Other amino acid NTs

• Glycine
  • Spinal cord interneurons
  • Also inhibitory
• Aspartate
  • Like Glu, stimulates NMDA receptor

Acetylcholine (ACh)

• Primary NT of CNS output
• Somatic nervous system (neuromuscular junction)
• Inactivated by acetylcholinesterase (AChE)

Acetylcholine (ACh)

• Autonomic nervous system
  • Sympathetic branch: preganglionic neuron
  • Parasympathetic branch: pre/postganglionic

Acetylcholine

Type	Receptor	Esp Permeable to	Blocked by
Ionotropic	Nicotinic (nAChR)	Na+, K+	e.g., Curare
Metabotropic	Muscarinic (mAChR)	K+	e.g., Atropine

Curare

Atropine

• also known as (aka), nightshade or belladonna
• blocks ACh receptors in muscles of the iris

Many ways to paralyze your prey

Substance	Effect
Japanese pufferfish toxin	Blocks voltage-gated Na+ channels
Black widow spider venom	Accelerates presynaptic ACh release
Botulinum toxin (BoTox)	Prevents ACh vesicles from binding presynaptically

Many ways to paralyze your prey

Substance	Effect
Sarin nerve gas	Impedes ACh breakdown by AChE
Pesticides	Impede AChE
Tetanus toxin	Blocks release of GABA, glycine

Monoamines

Family	Neurotansmitter
Monoamines	Dopamine (DA)
	Norepinephrine (NE)/Noradrenaline (NAd)
	Epinephrine (Epi)/Adrenaline (Ad)
	Serotonin (5-HT)
	Melatonin
	Histamine

Dopamine (DA)

• Released by two pathways
• Both originate in the midbrain tegmentum

Dopamine (DA)

• Substantia nigra -> striatum, meso-striatal projection
• Ventral tegmental area (VTA) -> nucleus accumbens, ventral striatum, hippocampus, amygdala, cortex; meso-limbo-cortical projection

Dopamine (DA)

• Disruption linked to
  • Parkinson’s Disease (mesostriatal)
    • DA agonists treat (agonists facilitate/increase transmission)
  • Schizophrenia (mesolimbocortical)
    • DA antagonists treat
  • Addiction (mesolimbocortical)
  • ADHD (mesolimbocortical)

Dopamine (DA)

• Inactivated by
  • Chemical breakdown
  • Dopamine transporter (DAT)

McHugh & Buckley (2015)

Dopamine (DA)

Type	Receptor	Comments
Metabotropic	D1-like (D1 and D5)	more prevalent
	D2-like (D2, D3, D4)	target of many antipsychotics (drugs that treat schizophrenia symptoms)

Dopamine (DA)

• Not the pleasure or motivation NT
• One function: signals differences between predicted and actual outcomes

Bell (2013)

Norepinephrine (NE)

• Role in arousal, mood, eating, sexual behavior
• Released by
  • locus coeruleus in pons/caudal tegmentum

Wikipedia

Norepinephrine (NE)

• Released by Sympathetic branch of Autonomic Nervous System (ANS) onto targets in PNS

Norepinephrine (NE)

• Monoamine oxidase (MAO) inactivates monoamines in neurons, glial cells
• Monoamine oxidase inhibitors (MAOIs) increase NE, DA
  • Inhibiting inactivation ~ -(-1) = + 1

Youdim, Edmondson, & Tipton (2006)

Norepinephrine (NE)

• MAO-Is early treatment for depression, but side effects (dry mouth, nausea, headache, dizziness)

Youdim et al. (2006)

Norepinephrine (NE)

Type	Receptor	Comments
Metabotropic	\(\alpha\) (1,2)	antagonists treat anxiety, panic
	\(\beta\) (1,2,3)	‘beta blockers’ in cardiac disease

Serotonin (5-HT)

• Released by raphe nuclei in brainstem
• Role in mood, sleep, eating, pain, nausea, cognition, memory
• Modulates release of other NTs

Wikipedia

Serotonin (5-HT)

• Most of body’s 5-HT neurons regulate digestion
  • via Enteric Nervous System (in PNS)

Furness (2012)

Serotonin (5-HT)

• 5-HT receptors
  • Seven families (5-HT 1-7) with 14 types
  • All but one metabotropic

Serotonin (5-HT)

• Ecstasy (MDMA) disturbs serotonin
• So does LSD
• Fluoxetine (Prozac)
  • Selective Serotonin Reuptake Inhibitor (SSRI)
  • Inhibits reuptake -> increases extracellular concentration
  • Treats depression, panic, eating disorders, others
• 5-HT3 receptor antagonists are anti-mimetics used in treating nausea

Melatonin

• Hormone released by pineal gland into bloodstream
• Concentrations vary over the day, peak near bedtime
• Release regulated by inputs from hypothalamus

Wikipedia

Key points about monoamines

• Monoamine neurotransmitters–DA, NE, 5-HT–modulate activity of other neurons
• Monoamines are released from specific areas in midbrain and hindbrain
• Monoamines project widely throughout the CNS
• Monamines are inactivated chemically and via transporters

Key points about monoamines

• Many drugs that treat psychiatric illness affect monoamines
• Most monoamines activate metabotropic receptors

Next time

• Wrap-up on neurochemistry
• Hormones

Resources

About

This talk was produced using Quarto, using the RStudio Integrated Development Environment (IDE), version 2025.5.1.513.

The source files are in R and R Markdown, then rendered to HTML using the revealJS framework. The HTML slides are hosted in a GitHub repo and served by GitHub pages: https://psu-psychology.github.io/psych-260-2025-fall/

References

Bell, V. (2013, February 3). The unsexy truth about dopamine. The Guardian. The Guardian. Retrieved from https://www.theguardian.com/science/2013/feb/03/dopamine-the-unsexy-truth

Furness, J. B. (2012). The enteric nervous system and neurogastroenterology. Nature Reviews. Gastroenterology & Hepatology, 9(5), 286–294. https://doi.org/10.1038/nrgastro.2012.32

Małgorzata, P., Paweł, K., Iwona, M. L., Brzostek, T., & Andrzej, P. (2020). Glutamatergic dysregulation in mood disorders: Opportunities for the discovery of novel drug targets. Expert Opinion on Therapeutic Targets, 24(12), 1187–1209. https://doi.org/10.1080/14728222.2020.1836160

McCutcheon, R. A., Krystal, J. H., & Howes, O. D. (2020). Dopamine and glutamate in schizophrenia: Biology, symptoms and treatment. World Psychiatry: Official Journal of the World Psychiatric Association, 19(1), 15–33. https://doi.org/10.1002/wps.20693

McHugh, P. C., & Buckley, D. A. (2015). Chapter eleven - the structure and function of the dopamine transporter and its role in CNS diseases. In G. Litwack (Ed.), Vitamins & hormones (Vol. 98, pp. 339–369). Academic Press. https://doi.org/10.1016/bs.vh.2014.12.009

Netflix, S. W. (2025). Dr. Jane Goodall’s final message to the world | famous last words | netflix. YouTube. Retrieved from https://www.youtube.com/watch?v=lfLKHY52ERc

Youdim, M. B. H., Edmondson, D., & Tipton, K. F. (2006). The therapeutic potential of monoamine oxidase inhibitors. Nature Reviews. Neuroscience, 7(4), 295–309. https://doi.org/10.1038/nrn1883