Cellular Neuroscience

2025-09-16

Rick Gilmore

Department of Psychology

Prelude

– Neural Academy (2020)

Today’s topics

  • Warm-up
  • Cells of the nervous system
  • Neurophysiology I

Warm-up

A dermatome is…

  • A. A receptor in the skin that signals itch.
  • B. A member of an 80’s punk band.
  • C. A sensory region of the frontal cortex.
  • D. A region of the skin innervated by a spinal nerve.

A dermatome is…

  • A. A receptor in the skin that signals itch.
  • B. A member of an 80’s punk band.
  • C. A sensory region of the frontal cortex.
  • D. A region of the skin innervated by a spinal nerve.

The spinal cord contains separate zones of gray and white matter.

  • A. True
  • B. False

The spinal cord contains separate zones of gray and white matter.

  • A. True
  • B. False

This branch of the autonomic nervous system is activated after you eat a big meal.

  • A. The somatic division of the CNS.
  • B. The parasympathetic branch of the ANS.
  • C. The sympathetic branch of the ANS.
  • D. The olfactory nerve (I).

This branch of the autonomic nervous system is activated after you eat a big meal.

  • A. The somatic division of the CNS.
  • B. The parasympathetic branch of the ANS.
  • C. The sympathetic branch of the ANS.
  • D. The olfactory nerve (I).

Cells of the nervous system

By the numbers…

Human vs. non-human cells

  • ~ 37 trillion (10^9) cells (Roy & Conroy, 2018)
  • 10-100 trillion non-human cells (gut, skin/hair, bloodstream, etc.)
  • Human bodies are a community

How many neurons and glia?

  • Old “lore”: ~100 billion (10^6) neurons
  • New estimate (Azevedo et al., 2009)
    • ~86 +/- 8 billion neurons
    • ~85 +/- 9 billion glia
  • 100-500 trillion synapses, 1 billion/mm^3

Tip

How long would it take you to count 170 billion cells?

How would you estimate how long?

  • 60 s/min x 60 min/hr x 24 hrs/day x 365 days/ yr = 31,536,000 s/yr
  • 1.7e11/31,536,000 = 5,390 years

“Back of the envelope” calculations/guess-timates are extremely useful–in science and in other aspects of life.

Quantifying the brain

Figure 2 from Azevedo et al. (2009)

Quantifying the brain

Non-neurons: Mass vs. number of cells

Quantifying the brain

Neurons: Mass vs. number of cells

Quantifying the brain

  • # of glial cells scales with brain size/mass
  • # of neurons doesn’t scale with brain size/mass
    • cerebellum small but # of neurons large

Quantifying the brain

“These findings challenge the common view that humans stand out from other primates in their brain composition and indicate that…the human brain is an isometrically scaled-up primate brain.”

– Azevedo et al. (2009)

Herculano-Houzel (2016)

Glia (neuroglia)

  • “Glia” means glue
  • Functions
    • Structural support
    • Metabolic support
    • Brain development
    • Neural plasticity?
  • Multiple types

Wikipedia; Neuron (yellow), astrocyte (green), oligodendrocyte (blue), microglia (reddish brown)

Astrocytes

Astrocytes

  • Regulate concentration of key ions (Ca++/K+) for neural communication
  • Regulate concentration of key neurotransmitters (e.g., glutamate)
  • Shape brain development, synaptic plasticity
  • Regulate local blood flow

https://en.wikipedia.org/wiki/Astrocyte

Astrocytes

Astrocytes

https://en.wikipedia.org/wiki/Astrocyte

Myelinating cells

  • Produce myelin or myelin sheath
    • White, fatty substance
    • Surrounds many neurons
    • The “white” in white matter

Wikipedia

Myelinating cells

  • Provide electrical/chemical insulation
  • Make neuronal messages faster, less susceptible to noise

Wikipedia

Oligodendrocytes

  • In brain and spinal cord (Central Nervous System or CNS)
  • 1:many neurons

Schwann cells

  • In Peripheral Nervous System (PNS)
  • 1:1 neuron

Schwann cells

https://www.brainfacts.org/brain-anatomy-and-function/cells-and-circuits/2018/schwann-cells-keep-signals-strong-012918

TV-show-inspired mnemonic

Central Oligodendrocytes Peripheral Schwann cells

TV-show-inspired mnemonic

Schwann cells Peripheral Oligodendrocytes Central

Microglia

  • Clean-up damaged, dead tissue
  • Prune synapses in normal development and disease
  • Disruptions -> impaired connectivity and social behavior (Zhan et al., 2014)

Wikipedia contributors (2025b)

Neurons

Figure 1: Neurons in mouse hippocampus: http://www.extremetech.com/wp-content/uploads/2012/03/a-mouse-hippocampus-640x353.jpg

Fun facts about neurons

Macrostructure of neurons

Dendrites

  • Branch-like “extrusions” from cell body
  • Majority of input to neuron
  • Cluster close to cell body/soma
  • Usually receive info
  • Passive (do not regenerate electrical signal) vs. active (regenerate signal)

Wikipedia contributors (2009)

Dendrites

  • Dendritic Spines (protrusions from dendrites)

Dendrites

  • “Polarized” or directional information flow (to soma)

https://askabiologist.asu.edu/neuron-anatomy

Soma (cell body)

  • Varied shapes
  • Nucleus
    • Chromosomes (genetic material)
  • Organelles
    • Mitochondria
    • Smooth and Rough Endoplasmic reticulum (ER)

Axons

  • Another branch-like “extrusion” from soma
  • Extend farther than dendrites
  • Usually transmit info

Axons

  • Parts
    • Axon hillock (closest to soma, unmyelinated)
    • Nodes of Ranvier (unmyelinated segments along axon)
    • Axon terminals, terminal buttons, synaptic boutons

Wikipedia contributors (2025a)

Synaptic bouton (terminal button)

  • Synapse (~5-10K per neuron)
  • Presynaptic membrane (sending cell) and postsynaptic (receiving cell) membrane
  • Synaptic cleft – space between cells

Synaptic bouton (terminal button)

Figure 1 from Torres, Gainetdinov, & Caron (2003)

Classifying neurons

  • Functional role
    • Input (sensory), output (motor/secretory), interneurons
  • Anatomy of axons
    • Unipolar
    • Bipolar
    • Multipolar

Classifying neurons

  • By specific anatomy
    • Pyramidal cells
    • Stellate cells
    • Purkinje cells
    • Granule cells

Pyramidal cell (Wikipedia)

Classifying neurons

Pyramidal cell (left) | Stellate cell (right) from Wikipedia

Neurophysiology I

Or how do neurons communicate?

Two communication ‘modes’

  • Electrical
    • Membrane potential (voltage) changes
  • Chemical
    • Neurotransmitter or hormone release

Electrical potential

  • Potential \(\rightarrow\) voltage
  • Voltage \(\approx\) pressure
  • Measure with
    • electrodes
    • Reference: outside

Electrical potential

  • Potential energy
    • Energy that could be released
    • If circumstances change

Neurons have electrical potential

  • Resting potential
    • Voltage across neuronal membrane when cell is ‘at-rest’ (not firing)
  • Action potential
    • Voltage across neuronal membrane when cell is active or firing

Neuron as a dynamical system

  • In a (temporarily stable) equilibrium
    • Not really at “rest”
  • Influenced by multiple forces
  • Forces balance-out (for now)

Metaphor I

Metaphor II

  • Annie/Alex (\(A^-\)) was having a party.
    • Used to date Nate/Natalie (\(Na^+\)), but now sees Karl/Kristie (\(K^+\))
  • Hired bouncers called
    • “The Channels”
    • Let Karl/Kristie and friends in or out, keep Nate/Natalie out

Metaphor II

  • Annie/Alex’s friends (\(A^-\)) and Karl/Kristie’s (\(K^+\)) mostly inside
  • Nate/Natalie and friends (\(Na^+\)) mostly outside
  • Claudia/Claude (\(Cl^-\)) tagging along

Studying systems in equilibrium

  • What are the forces?
  • How do the forces act on the system individually?
  • How do the forces act on the system collectively?
  • What happens when the forces or the balance among them changes?

Resting potential

  • Ions (charged particles)
    • Potassium, \(K^+\)
    • Sodium, \(Na^+\)
    • Chloride, \(Cl^-\)
    • Organic anions, \(A^-\)
  • Ion channels
    • Molecular gateways or doors

Resting potential

  • Separation between charges
    • Positive and negative charges spatially separated
  • A balance of forces
    • Force of diffusion
    • Electrostatic force
  • Forces cause ion flows across membrane
    • Force of diffusion consistent (over time)
    • Electrostatic force changes

Ion channels

  • Openings in neural membrane
  • Selective for specific ions
  • Vary in permeability (how readily ions flow)
    • Some ions can flow more easily than others at different times

Ion channels

  • Types
    • Ligand-gated (chemically-gated)
    • Mechanically-gated
    • Passive/leak (always open)
    • Voltage-gated

Na+/K+ “pump”

  • Also known as Na+/K+-ATPase
  • Moves ions across membrane
  • With metabolic “help” (energy expenditure)

Metaphor III

Figure 6 from Kaunda, Kimambo, & Nielsen (2012)

Neuron at rest permeable to \(K^+\)

  • [\(K^+\)] concentration inside >> outside
    • Na+/K+ pump moves it in
  • Permeable: Permits flow across/through
  • Passive \(K^+\) channels open
  • \(K^+\) flows out
    • Neuron constantly brings \(K^+\) in

Force of diffusion

Wikipedia

A practical illustration of the force of diffusion.

Wikipedia
  • Organic anions (\(A^-\)) too large to move outside of cell
  • \(A^-\) and \(K^+\) largely in balance == no net internal charge
  • \(K^+\) outflow creates charge separation: \(K^+\) (outside) <-> \(A^-\) (inside)
  • Charge separation creates a voltage
  • Outside +/inside -
  • Voltage build-up stops outflow of \(K^+\)

The resting potential

Balance of forces in the neuron at rest

  • Force of diffusion
    • \(K^+\) moves from high concentration (inside) to low (outside)

Balance of forces in the neuron at rest

  • Electrostatic force
    • Voltage build-up stops \(K^+\) outflow
    • Specific voltage that stops flow == equilibrium potential for \(K^+\)+
    • \(K^+\) positive, so equilibrium potential negative (w/ respect to outside)
    • Equilibrium potential close to neuron’s resting potential

Note

In PSYCH 260, we do not emphasize the calculation of equilibrium potentials and the Nernst equation or the Goldman-Hodgkin-Katz equation.

We provide information about this, and the equivalent circuit model, in the next few slides for your reference.

Equilibrium potential

Equilibrium potentials calculated under typical conditions

Ion [inside] [outside] Voltage
\(K^+\) ~150 mM ~4 mM ~ -90 mV
\(Na^+\) ~10 mM ~140 mM ~ +55-60 mV
\(Cl^-\) ~10 mM ~110 mM - 65-80 mV
  • Magnitude and sign of voltage indicates which direction a given ion will “drive” the neuron

Nernst equation

Neuron resting potential ≠ \(K^+\) equilibrium potential

  • Resting potential not just due to \(K^+\)
  • Other ions flow
  • Resting potential == net effects of all ion flows across membrane

Goldman-Hodgkin-Katz equation

\(Na^+\) role

  • \(Na^+\) concentrated outside neuron
  • Membrane at rest not very permeable to \(Na^+\)
  • Some, but not much \(Na^+\) flows in
  • \(Na^+\) has equilibrium potential ~ + 60 mV

\(Na^+\) role

  • Equilibrium potential is positive (with respect to outside)
  • Would need positive interior to keep \(Na^+\) from flowing in

Electrical circuit model

Wikipedia

Summary of forces in neuron at rest

Ion Concentration gradient Force of diffusion Sign of electrostatic force
\(K^+\) \([K^+]_{i} >> [K^+]_{o}\) outward -
\(Na^+\) \([Na^+]_{i} << [Na^+]_{o}\) inward -

Next time

  • Neurophysiology II

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

Azevedo, F. A., Carvalho, L. R., Grinberg, L. T., Farfel, J. M., Ferretti, R. E., Leite, R. E., et al.others. (2009). Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. Journal of Comparative Neurology, 513(5), 532–541. https://doi.org/10.1002/cne.21974
Bazargani, N., & Attwell, D. (2016). Astrocyte calcium signaling: The third wave. Nature Neuroscience, 19, 182–189. https://doi.org/10.1038/nn.4201
Bhardwaj, R. D., Curtis, M. A., Spalding, K. L., Buchholz, B. A., Fink, D., Björk-Eriksson, T., … Frisén, J. (2006). Neocortical neurogenesis in humans is restricted to development. Proceedings of the National Academy of Sciences of the United States of America, 103, 12564–12568. https://doi.org/10.1073/pnas.0605177103
Chung, W.-S., Welsh, C. A., Barres, B. A., & Stevens, B. (2015). Do glia drive synaptic and cognitive impairment in disease? Nature Neuroscience, 18(11), 1539–1545. https://doi.org/10.1038/nn.4142
Herculano-Houzel, S. (2016). The Human Advantage: A New Understanding of How Our Brain Became Remarkable. MIT Press. Retrieved from https://market.android.com/details?id=book-DMqpCwAAQBAJ
Kaunda, C. S., Kimambo, C. Z., & Nielsen, T. K. (2012). Hydropower in the context of sustainable energy supply: A review of technologies and challenges. ISRN Renewable Energy, 2012, 1–15. https://doi.org/10.5402/2012/730631
Magrassi, L., Leto, K., & Rossi, F. (2013). Lifespan of neurons is uncoupled from organismal lifespan. Proceedings of the National Academy of Sciences, 110, 4374–4379. https://doi.org/10.1073/pnas.1217505110
Neural Academy. (2020). THE NEURON SONG. Youtube. Retrieved from https://www.youtube.com/watch?v=R0SZnLOeh5E
Roy, A. L., & Conroy, R. S. (2018). Toward mapping the human body at a cellular resolution. Molecular Biology of the Cell, 29, 1779–1785. https://doi.org/10.1091/mbc.E18-04-0260
Torres, G. E., Gainetdinov, R. R., & Caron, M. G. (2003). Plasma membrane monoamine transporters: Structure, regulation and function. Nature Reviews. Neuroscience, 4(1), 13–25. https://doi.org/10.1038/nrn1008
Wikipedia contributors. (2009, February 24). Dendrite. Retrieved from https://simple.wikipedia.org/wiki/Dendrite
Wikipedia contributors. (2025a, June 13). Node of ranvier. Retrieved from https://en.wikipedia.org/wiki/Node_of_Ranvier
Wikipedia contributors. (2025b, July 28). Microglia. Retrieved from https://en.wikipedia.org/wiki/Microglia
Zhan, Y., Paolicelli, R. C., Sforazzini, F., Weinhard, L., Bolasco, G., Pagani, F., … Gross, C. T. (2014). Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nature Neuroscience, 17, 400–406. https://doi.org/10.1038/nn.3641