Main points
- Behavior in complex multicellular organisms builds upon their \(\approx 4 B\) year history
- (Slower) chemical communication via diffusion
- (Faster) Electrical communication along membrane via ion flows
Cells of the nervous system
PSY 511.001 Spr 2026
Learn
So, why nervous systems?
- Chemical communication specific (neurotransmitters \(\rightarrow\) receptors)
- Energy efficient
- But slow
- Bigger bodies \(\rightarrow\) fast(er) communication
- To/from periphery
Who (what) am I?
- 20,000-25,000 human genes
- \(\approx\) 2-20 million genes in non-human “metagenome”
- Human Microbiome Project Consortium (2012); Tierney et al. (2019)
- humans as supraorganisms (Gilbert, Sapp, & Tauber, 2012)
“These findings challenge the common view that humans stand out from other primates in their brain composition and indicate that, with regard to numbers of neuronal and nonneuronal cells, the human brain is an isometrically scaled-up primate brain.”
– Azevedo et al. (2009)
Glia (neuroglia)
- “Glia” means glue
- Functions
- Structural support
- Metabolic support
- Brain development
- Neural plasticity?
- Multiple types
Astrocytes
- “Star”-shaped cells
- Physical and metabolic support
- Support blood/brain barrier
- Regulate local blood flow & oxygen
Astrocytes
- Interact with neurons
- Ion (Ca++/K+) buffering
- Neurotransmitter (e.g., glutamate) buffering
- Regulate/influence communication between neurons (Bazargani & Attwell, 2016)
Astrocytes
- Disruption linked to cognitive impairment, disease (Chung, Welsh, Barres, & Stevens, 2015)
Myelinating cells
Myelin
- outer covering of neurons
- provided by separate class of glial cell
- increases the speed of signal (action potential) conduction.
- found in all vertebrates3
- The white in white matter
See also: https://en.wikipedia.org/wiki/Myelin
Oligodendrocytes
Oligodendrocytes
Schwann cells
- In peripheral nervous system (PNS)
- 1:1 neuron
TV-show-inspired mnemonic
Central Oligodendrocytes Peripheral Schwann cells
TV-show-inspired mnemonic
Schwann cells Peripheral Oligodendrocytes Central
Microglia
Microglia
- Role in multiple sclerosis (MS) (Distéfano-Gagné, Bitarafan, Lacroix, & Gosselin, 2023)
- Disruptions -> impaired connectivity and social behavior (Zhan et al., 2014)
Neurons
Macrostructure
- Dendrites
- Soma
- Axons
- Terminal buttons (boutons)
Dendrites
- Majority of input to neuron
- Passive (do not generate current flows) vs. active (generate current flows like axons)
Dendrites
- “Polarized” or directional information flow (to soma)
Dendritic Spines
Soma (cell body)
- Varied shapes
- Nucleus
- Chromosomes
- 70-84% of human genes expressed in the brain (Negi & Guda, 2017)
Soma (cell body)
- Nucleus
- Mitochondria
- Source of Adenosine Triphosphate (ATP), chemical energy
- Smooth and Rough Endoplasmic reticulum (ER)
- Synthesis of proteins, lipids, calcium storage, …
- Mitochondria
Axons
- Another branch-like “extrusion” from soma
- Extend farther than dendrites
- Usually transmit info
Axon components
- Axon initial segment (closest to soma, unmyelinated)
- Nodes of Ranvier (unmyelinated segments along axon)
- Axon terminals, terminal buttons, synaptic boutons
Synaptic bouton (terminal button)
- Synapse (~1-1,000s/neuron)
- Pre- (sending side) and postsynaptic (receiving side) membranes
- Synaptic cleft
- Synaptic vesicles
- Store/release neurotransmitters
Autoreceptors & transporters
Classifying neurons
- Functional role
- Input (sensory), output (motor/secretory), interneurons
- Anatomy of axons
- Unipolar
- Bipolar
- Multipolar
Classifying neurons
Classifying neurons
Morphology, physiology, gene transcription
Basic principles
- Electrical potential (== voltage)
- Think of potential energy
- Voltage ~ pressure
- Energy that will be released if something changes
Basic principles
- Current flow (\(I\)) across membrane
- Resistors resist current flow
- Product \(IR\) is electromotive force (\(E\)) or voltage
- Resistors dissipate (as heat) energy stored in voltage source
\[E = IR\]
Basic principles
- A capacitor (\(C\)) accumulates electrical charge
- Stores & releases charge
- Camera flash uses a capacitor
Measuring electrical potential
- In the neuron
- Electrode on inside
- Electrode on outside (reference)
- Inside - Outside = potential
Neurons have electrical potential
- Have potential energy
- Resting potential
- Voltage across neuronal membrane when cell is ‘at-rest’ (not firing)
- Inside typically -60-70 mV, with respect to outside
- ~1/20th typical \(1.5V\) AA battery
Metaphor I
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
Ion channels
- Macromolecules that form openings in membrane
- Different types of subunits
- Selective (permit some ions to flow)
- Vary in permeability (allow some substances to pass more than others)
Ion channels
- Types
- Passive/leak
- Voltage-gated
- Ligand-gated (chemically-gated)
- Transporters
Na+/K+ “pump”
- Also known as Na+/K+-ATPase
- Moves ions across membrane
- With metabolic “help” (energy expenditure)
Metaphor III
Forces at work I
Forces at work II
- “Metabolic” force via Na/K-ATPase
- 3 \(Na^+\) out : 2 \(K^+\) in
- Creates/sustains ion concentration imbalances
Forces at work III
- Electrostatic force
- Movement of charged particles (ions) == current
- Like charges repel; opposite charges attract
- Build-up of charges along membrane creates a voltage
Electrostatic force
- Membrane acts like a capacitor
Focus on \(K^+\)
- \(K^+\) ions move outward
- Line up along outside of membrane
- \(A^-\) ions can’t escape
- line up along inside
Focus on \(K^+\)
- Flow stops at equilibrium potential
- Equilibrium potential for \(K^+ \approx -90mV\)
- Nernst equation14
Story so far
- Na/K-ATPase creates inside/outside concentration differences
- Outflow of \(K^+\) \(\rightarrow\) a negative membrane potential
Your turn
- Resting potential is \(\approx\) -60-70 mV, more positive than the -90 mV that would stop \(K^+\) outflow
- Why?
Focus on \(Na^+\)
- Flow stops at equilibrium potential for \(Na^+\)
- Calculate using Nernst equation
Your turn
What is the sign of the equilibrium potential for \(Na^+\)
Or, what inside/outside voltage would stop the inflow of \(Na^+\)?
Metaphor I
A combination of forces
- Calculate net effects of ion flow across membrane via
- Goldman-Hodgkin-Katz equation
From rest to action
- What ion has the strongest driving force when the neuron is at resting potential?
- Which way will that ion flow?
- What will happen to the membrane potential if flow for that ion increases?
From rest to action
- What change(s) could alter the neuron’s equilibrium state (change the resting potential)?
Footnotes
“Timeline of Key Human Neurodevelopmental Processes and Functional Milestones.”
Neuron (yellow), astrocyte (green), oligodendrocyte (blue), microglia (reddish brown)
except jawless fish
“A neuron cell diagram, cropped to show oligodendrocyte and myelin sheath. By Neuron_with_oligodendrocyte_and_myelin_sheath.svg: *Complete_neuron_cell_diagram_en.svg: LadyofHatsderivative work: Andrew c (talk) - Neuron_with_oligodendrocyte_and_myelin_sheath.svg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=10888009.”
“An oligodendrocyte seen myelinating several axons. By Artwork by Holly Fischer - http://open.umich.edu/education/med/resources/second-look-series/materials - CNS Slide 9, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=24367135”
“Rat microglia grown in tissue culture in green, along with nerve fiber processes shown in red. By GerryShaw - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17504964.”
“Spines on the dendrite of a medium spiny striatal neuron. The image was obtained by expressing Enhanced Green Fluorescent Protein (EGFP) in the neurons and imaging them using a laser scanning two photon microscope. By http://en.wikipedia.org/w/index.php?title=User:Tmhoogland&action=edit - http://en.wikipedia.org/wiki/Image:Spines.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1826453”
“Monoamine transporters are localized to perisynaptic sites, where they are crucial for the termination of monoamine transmission and the maintenance of presynaptic monoamine storage. Several selective pharmacological agents acting at each monoamine transporter are shown. Amph., amphetamine; DA, dopamine; DAT, Dopamine transporter; L-DOPA, L-3,4-dihydroxyphenylalanine; 5-HT, 5-hydroxytryptamine; MPP+, 1-methyl-4-phenylpyridinium; MDMA, (+)-3,4-methylenedioxymethamphetamine; NA, noradrenaline; NET, noradrenaline transporter; SERT, 5-HT transporter”
“A human neocortical pyramidal cell stained via Golgi’s method. The apical dendrite extends vertically above the soma (cell body) and the numerous basal dendrites radiate laterally from the base of the cell body. Photo by Bob Jacobs, Laboratory of Quantitative Neuromorphology Department of Psychology Colorado College https://www.coloradocollege.edu/basics/contact/directory/people/jacobs_bob.html.”
“Neurons can be classified using morphological, physiological and molecular criteria. a | Representative examples of five subclasses of cortical neurons obtained from brain slices. The cells were filled with biocytin, stained and imaged following patch clamp recording (see part b). Each subclass has distinct morphological features. For the four interneurons on the left, the dendrites are shown in dark grey and the axons in light grey. The soma of the 5-hydroxytryptamine receptor 3A-expressing (HTR3A+) sparse neuro- gliaform cell is located in layer 1, and its axons are also concentrated in this layer. The vasoactive intestinal peptide-expressing (VIP+) bipolar cell has a characteristic bipolar dendritic extension. The soma of the somatostatin-expressing (SST+) deep Martinotti cell is located in layer 5/6, and its axons extend upward into layer 1. The parvalbumin-expressing (PVALB+) basket cell has basket-like axonal arborisation. For the excitatory neuron on the right, the apical dendrites are shown in dark grey and the basal dendrites in light grey. This is a layer 5, thick-tufted cell from a retinol-binding protein 4 (Rbp4) gene promoter-driven Cre-expressing mouse. The cell features thick apical dendritic tufts extending into layer 1. These morphological features are consistent with those described in published reports49,130,140. b | Differential electrophysiological responses of the five subclasses of neurons shown in part a to square pulses of current in patch clamp recordings. For example, the HTR3A+ cell is late spiking, whereas the PVALB+ cell is fast spiking. These responses are consistent with those described in published reports49,130,140. c | Differential molecular signatures of the five subclasses of cortical neurons illustrated in part a derived from single-cell RNA-sequencing data. The violin plot shows the collective gene expression profile for each gene of all the cells in a type (cluster). We define the smallest discrete clusters of cells as types and the aggregates of types that share common features as classes or subclasses. Each transcriptomic cell type is shown as a column of data points with the same colour (the colour coding corresponds to that of the transcriptomic taxonomy shown in Fig. 5). Shown here are three interneuron cell types expressing Htr3a but notVip, six interneuron cell types expressing Vip, six interneuron cell types expressing Sst and seven interneuron cell types expressing Pvalb. All of the interneurons express glutamate decarboxylase 1 (Gad1). Also shown are eight layer 5 excitatory neuron types, all of which express solute carrier family 17 member 7 (Slc17a7). All of the cells express synaptosome-associated protein 25 (Snap25). The height of each ‘violin’-shaped data point represents the range of expression levels of the gene, and the width represents the proportion of cells displaying a particular level of expression. Parts a and b are from the Allen Cell Types Database (see Further Information). Part c is adapted with permission from Ref. 136.”
“The figure shows a proposed hierarchical classification of cells in the retina (a) and cerebral cortex (b). In both areas, individual cell types can be grouped into classes, and intermediate levels of subclasses can be determined based on distinct morphological, physiological and molecular features. Higher-order groupings (such as those shown in part a, including sensory neurons, interneurons and projection neurons) may emerge once enough areas have been provided and compared. Types are the commonly recognized (‘validated’) terminal branches in the current hierarchical arrangement of cell types. Lower-order groupings into subtypes may largely be provisional until additional data are collected that could determine if they could form new types or should be merged into other types. Dashed lines indicate the presence of additional types that cannot be labelled due to lack of space. The question marks in part a indicate that the hierarchical relationship among the indicated cell types remains unclear. The question mark in part b indicates that the status of the cortical cell groups indicated may be either subclasses, types or subtypes. CT, cortico-thalamic neurons; DS, direction-selective retinal ganglion cells (RGCs); F, forkhead box P2 (Foxp2)-expressing RGCs; HTR3A, 5-hydroxytryptamine receptor 3A; ipRGC, intrinsically photosensitive RGCs; IT, intratelencephalic neurons; L4, layer 4; L6b, layer 6b subplate neurons; nGnG, non-GABAergic-non-glycinergic amacrine cells; ooDSGC, ON-OFF direction-selective RGCs; PT, pyramidal tract neurons; PVALB, parvalbumin; SST, somatostatin; VIP, vasoactive intestinal peptide.”
“a, Examples of different firing patterns induced by current injections in layer 1 interneurons. Firing pattern of an RC (top), an NGFC (middle), and an unidentified layer 1 interneuron (bottom). b, SVM-based wrapper-feature selection of electrophysiological parameters for the identification of RCs. Anatomically identified RCs (red dots) and other types of interneurons with known morphology (black dots) are mapped to the distribution of electrophysiological features ranked as the two best delineators by SVM. Black lines show the best hyperplane separating RCs from other interneuron types. c,d, RCs exhibit a distinct impedance profile relative to neurogliaform and other human interneurons in layer 1. (c) Individual responses of anatomically identified rosehip (red), neurogliaform (blue), and other (black) interneurons to current injections with an exponential chirp (0.2–200 Hz; top). Traces were normalized to the amplitude of the rosehip response at 200 Hz. (d) Left: normalized impedance (Z) profiles of distinct groups of interneurons. RCs (n=5) had higher impedance in the range of 0.9–12.4 Hz compared to neurogliaform (n=5) and other (n=5) interneurons. Shaded regions represent s.d. Right: impedances were similar at the lowest frequency (Z0.2 Hz; left), but resonance magnitude (Q) calculated as maximal impedance value divided by the impedance at lowest frequency (middle) and frequencies of maximal impedance (fmax; right) showed significant differences (P < 0.05, ANOVA with Bonferroni post hoc correction). e, Automatized selection of recording periods for assessing subthreshold membrane potential oscillations (boxed segments) and detection of bursts (bars) for measuring intraburst spiking frequency demonstrated on an RC response to near-rheobasic stimulation showing stuttering firing behavior. f, Averaged fast fast Fourier transforms (FFTs) of membrane potential oscillations had higher power between 3.8 and 80 Hz in RCs compared to neurogliaform and other interneurons. g, Intraburst frequency of RCs peaked in the gamma range. AP, action potential.”
“Some particles are dissolved in a glass of water. At first, the particles are all near one top corner of the glass. If the particles randomly move around (”diffuse”) in the water, they eventually become distributed randomly and uniformly from an area of high concentration to an area of low, and organized (diffusion continues, but with no net flux). By JrPol - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=4586487”
Note that the outside/inside concentration ratio < 1. The log of a number < 1 is negative.
