Neurochemistry

2025-09-30

Rick Gilmore

Department of Psychology

Prelude

– LadyGagaVEVO (2021)

Today’s topics

  • Announcements
    • No class Thursday, October 2, 2025
  • Comment on Quiz 1
  • Behavior requires communication
  • Synaptic communication
  • Neurotransmitters

Comment on Quiz 1

9. Electroencephalography (EEG) has ___ temporal resolution than functional MRI, but ___ spatial resolution.

  • A. better; similar
  • B. better; worse
  • C. worse; better
  • D. worse; similar

9. Electroencephalography (EEG) has ___ temporal resolution than functional MRI, but ___ spatial resolution.

  • A. better; similar
  • B. better; worse
  • C. worse; better
  • D. worse; similar

Back story

  • Electroencephalograpy (EEG) & magnetoencephalography (MEG) rely on electromagnetic (EM) signals
  • Large numbers of overlapping action potentials generate EM signals
  • EM signals propagate quickly through brain, skull, & scalp
  • High temporal resolution (>> fMRI)
  • But, EM sources distributed widely, so low spatial resolution (<< fMRI)

Behavior requires communication

Types of communication for behavior

  • Between organisms
  • Within organisms
    • Sensors (eyes, ears, skin, …)
    • Effectors (muscles, glands)
    • Linked via CNS

What do animals need to know to behave?

  • What’s out there
  • Where is it
  • What should I do about it
  • Do it

Nervous systems are communication systems

  • Chemical communication : short distances
    • Force of diffusion
    • Cheap, energy-efficient, “compute with chemistry”
  • Electrical communication : long distances
    • Ion flows across membrane \(\rightarrow\) propagating voltages
    • More “expensive” (metabolically-speaking)/less energy-efficient
    • Much faster

– Sterling & Laughlin (2021)

Nervous systems are communication systems

  • Synaptic communication
    • Chemical (via neurotransmitters)
    • Electrical (via ion flow)
  • Endocrine communication (chemical via hormones released into bloodstream)

Synaptic communication

Steps in synaptic transmission

Step
Action potential arrives at terminal button.
Voltage-gated \(Ca^{++}\) channels open
\(Ca^{++}\) ions enter the cell
\(Ca^{++}\) ions activate synaptic vesicles & trigger exocytosis

Steps in synaptic transmission

Step
Neurotransmitter diffuses across synaptic cleft
Neurotransmitter binds to post-synaptic receptor(s)
Postsynaptic receptor(s) cause EPSP or IPSP
Neurotransmitter unbinds and is inactivated

Action potential propagates from soma

  • Soma receives input from dendrites
  • Axon hillock sums/integrates
  • If sum > threshold, AP “fires”

Wikipedia

Action potential propagates from soma

  • AP propagates
  • Quickly: myelinated + thick axon
  • Slowly: unmyelinated or thin

– Neuron (2021)

Action potential arrives at synaptic terminal

  • How does AP cause chemical release?
  • Voltage-gated calcium (Ca++) channels open
  • Ca++ enters

Action potential arrives at synaptic terminal

  • Ca++ causes synaptic vesicles to bind with presynaptic membrane & merge with it
  • Neurotransmitters (NTs) released via exocytosis (‘out’ of the cell)

Hastoy, Clark, Rorsman, & Lang (2017)

(Hastoy et al., 2017)

Wikipedia

NTs cross the synaptic clef

  • NTs bind with receptors on postsynaptic membrane
  • Receptors respond
  • NTs unbind, are inactivated

Wikipedia

Synaptic vesicles get “recycled”

  • Vesicles reform
  • Get refilled with neurotransmitter

(Haucke, Neher, & Sigrist, 2011)

Why do NTs move from presynaptic terminal toward postsynaptic cell?

  • Electrostatic force pulls them
  • Force of diffusion
  • Synaptic cleft small relative to vesicles, so diffusion time short (< 0.5 ms)

Postsynaptic receptor types

  • Ionotropic (receptor + ion channel)
    • Chemical (ligand)-gated
    • Open/close ion channel
    • Ions flow in/out depending on membrane voltage and ion type
    • Fast-responding (< 2 ms), but short-duration effect (< 100 ms)

Postsynaptic receptor types

  • Metabotropic (receptor only, no attached ion channels
    • Trigger G-proteins attached to receptor
    • G-proteins activate 2nd messengers

Postsynaptic receptor types

  • Metabotropic (receptor only, no attached ion channels
    • 2nd messengers bind to, open/close adjacent channels or change metabolism
    • Slower, but longer-lasting effects

Receptors cause response

  • Generate postsynaptic potentials (PSPs)
    • Small voltage changes
    • Amplitude scales with # of receptors activated
    • Number of receptors activated ~ # of vesicles released

http://pittmedneuro.com/synaptic.html

Two types of postsynaptic potentials (PSPs)

  • Excitatory PSPs (EPSPs)
    • Depolarize neuron (make more +)
    • Move membrane potential closer to threshold

http://pittmedneuro.com/synaptic.html

Two types of postsynaptic potentials (PSPs)

  • Inhibitory (IPSPs)
    • Hyperpolarize neuron (make more -)
    • Move membrane potential away from threshold

http://pittmedneuro.com/synaptic.html

Message from dendrites & soma

  • a mixture of IPSPs and EPSP

Wikipedia

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)

What sort of PSP would opening a Cl- channel produce?

Remember \([Cl^-]_{out}>>[Cl^-]_{in}\); Assume resting potential ~-60 mV. Cl- is negatively charged, so will have opposite effect of positively charged ions.

  • Cl- flows in, so Excitatory PSP (EPSP)
  • Cl- flows out, so Excitatory PSP (EPSP)
  • Cl- flows in, so Inhibitory PSP (IPSP)
  • Cl- flows out, so Inhibitory PSP (IPSP)

What sort of PSP would opening a Cl- channel produce?

Remember \([Cl^-]_{out}>>[Cl^-]_{in}\); Assume resting potential ~-60 mV. Cl- is negatively charged, so will have opposite effect of positively charged ions.

  • Cl- flows in, so Excitatory PSP (EPSP)
  • Cl- flows out, so Excitatory PSP (EPSP)
  • Cl- flows in, so Inhibitory PSP (IPSP)
  • Cl- flows out, so Inhibitory PSP (IPSP)

NT inactivated by multiple mechanisms

  • Buffering
  • Reuptake via transporters
    • molecules in membrane that move NTs inside
    • e.g., serotonin via serotonin transporter (SERT)

NT inactivated by multiple mechanisms

  • Enzymatic degradation
    • e.g., Acetylcholinesterase (AChE) degrades acetylcholine (ACh)

Why must NTs be inactivated?

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

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))

Neurotransmitters

What are they?

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

Glutamate

Glutamate

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

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

  • Primary inhibitory NT in CNS
  • Excitatory in developing CNS, \([Cl^-]_{in} >> [Cl-]_{out}\)
  • 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+

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 receptors in the muscles of your 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

Main points

  • Neurons use electrical communication (action potentials) to communicate quickly over long distances
  • Chemical communication (diffusion) to communicate over short distances
  • Neurotransmitters are special chemicals that neurons release onto other neurons
  • Ionotropic and metabotropic receptors generate EPSPs and IPSPs
  • Amino acid neurotransmitters: glutamate, GABA, ACh

Next time

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

Anderson, C. M., & Swanson, R. A. (2000). Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia, 32(1), 1–14. https://doi.org/10.1002/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W
Hastoy, B., Clark, A., Rorsman, P., & Lang, J. (2017). Fusion pore in exocytosis: More than an exit gate? A \(\beta\)-cell perspective. Cell Calcium, 68, 45–61. https://doi.org/10.1016/j.ceca.2017.10.005
Haucke, V., Neher, E., & Sigrist, S. J. (2011). Protein scaffolds in the coupling of synaptic exocytosis and endocytosis. Nature Reviews. Neuroscience, 12(3), 127–138. https://doi.org/10.1038/nrn2948
LadyGagaVEVO. (2021). Tony bennett, lady gaga - I get a kick out of you (official music video). Youtube. Retrieved from https://www.youtube.com/watch?v=iTdHQ065A_o&list=RDiTdHQ065A_o&start_radio=1
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
Neuron, N. (2021). Propagation of action potential. Youtube. Retrieved from https://www.youtube.com/watch?v=tOTYO5WrXFU
Sterling, P., & Laughlin, S. (2021). Principles of neural design. The MIT Press, Massachusetts Institute of Technology. Retrieved from https://mitpress.mit.edu/books/principles-neural-design