Notes on Synapses, Sherrington, and Course Design

Course Context: class feedback and design

  • Word cloud of team expectations over years highlights themes: communication, respect, effort, among others.
  • AI summarized survey results about student interests and career aims:
    • Medical and clinical professions: about 16 respondents
    • Psychiatry and clinical psychology: about 11 respondents
    • Academic and research (including research, graduate school, higher education professor): about 9 respondents
    • Law and forensics: about 6 respondents
    • Other health care: about 3 respondents
  • Why students take the class and what they hope to learn:
    • Interest in the topic; some students have it as a required course due to positive prior feedback; broad interest in foundational knowledge about how the human body works.
    • Goals include foundational understanding, career and academic learning progression, exploring mental health, and personal growth.
    • Plan to build from the basics at the start of the course and develop to more advanced topics later.
  • Thoughts on course design:
    • Positive aspects: collaborative, interactive elements, structured learning, and support for learning.
  • Specific points for consideration:
    • Exam weight: some would prefer less emphasis; instructor notes most students have done well with current weighting.
    • Group work: one student dislikes semester-long group work and prefers to work alone; others suggest smaller groups. Real-world analogy: teamwork is a life skill, so the single-output-for-a-team format mirrors professional settings.
    • Real-world classroom analogy: university classroom is a form of real-world experience; good practice for teamwork and producing outputs.
  • Lecture materials and accessibility:
    • Some bullet points on slides were hard to follow; instructor pasted the summary from the textbook to aid readability.
    • A general summary for the whole chapter is included on the final summary slide.
  • Access to lectures:
    • Some students asked for recorded lectures or live Zoom links for days they cannot attend in person.
    • Rationale for keeping in-person attendance: most material is in the textbook; some topics can be controversial, and students should feel free to ask questions.
    • Emphasis on notetaking support: discussion about notetakers for peers; a message will be shared to recruit volunteers.
  • Open questions environment:
    • Students encouraged to ask any questions, including “stupid questions”; instructor values curiosity and humor (anonymized examples discussed briefly without harm).
  • Practical note: if a student misses a class, it’s not a big deal; questions can be addressed afterward through Sam or the instructor.

Today's focus and learning objectives

  • Today’s topic: the synapse; Chapter 2.1.
  • Learning objective: understand the synapse as a specialized structure enabling communication between neurons.
  • Historical anchor: Charles Sherrington, Nobel Prize in Physiology or Medicine (1932), a foundational figure in synaptic physiology.

Charles Sherrington and the synapse

  • Sherrington’s contribution:
    • Identified the synapse as the communication junction between neurons, transforming electrical signals into chemical signals to enable inter-neuronal communication.
    • Studied reflexes in dogs to investigate neural communication; introduced the concept of the reflex arc.
  • Reflex arc concept:
    • Example: leg flexion reflex where a sensory neuron excites a second neuron, which excites a motor neuron, which stimulates muscle contraction.
    • Focus on response time: measured how long it takes for a dog to retract its leg when stimulated.
  • Key observation leading to the synapse concept:
    • Reflexes were slower than the conduction speed along a single axon.
    • If a reflex were produced by a single axon, it would be nearly instantaneous; the observed delay suggested a communication step beyond a single axon.
    • Inference: there must be multiple synapses slowing the signal, enabling modulation.
  • Measured speeds and implication:
    • Axonal conduction speed (unmyelinated or myelinated fibers): about
      vaxon≈40 m/sv_{axon} \approx 40\ \text{m/s}
    • Reflex arc conduction speed: sometimes as slow as
      vreflex≈15 m/s or lessv_{reflex} \approx 15\ \text{m/s} \text{ or less}
    • The additional delay is attributed to synapses at various points in the reflex pathway.
  • Significance: synapses allow for modulation, integration, and more complex responses than a pure electrical relay would permit.

Temporal and spatial summation

  • Core idea: postsynaptic neuron integrates inputs from multiple synapses over time and space.
  • Temporal summation:
    • Repeated stimuli over a short period produce a stronger response than a single input.
    • Basis: successive EPSPs accumulate before the membrane potential returns to baseline.
  • Spatial summation:
    • Multiple inputs onto a single postsynaptic neuron can combine to push the membrane potential past the threshold.
    • Inputs can arrive from different presynaptic neurons simultaneously.
  • EPSP concept:
    • Excitatory postsynaptic potential: a small depolarization of the postsynaptic membrane that moves toward the threshold but may not reach it on its own.
    • Resting potential example:
      Vrest=−70 mVV_{rest} = -70\ \text{mV}
    • An EPSP might depolarize toward, for example,
      −60 mV-60\ \text{mV}, though the exact threshold value is neuron-dependent.
  • Post-synaptic potential decay:
    • EPSP and IPSP are graded changes that decay in time and space.
    • The net effect is the sum of all inputs at the axon hillock, which determines whether an action potential is fired.
  • Axon hillock as the integrator:
    • The axon hillock integrates dendritic and somatic inputs
    • If the integrated membrane potential reaches the threshold, an action potential is generated and travels down the axon with a fixed all-or-none property.
  • Visualizing the concept (graph described): three traces on a graph showing subthreshold EPSPs and their cumulative effects:
    • A: one subthreshold EPSP
    • B: two consecutive subthreshold EPSPs
    • C: three consecutive EPSPs reaching threshold and triggering an action potential
  • Terminology recap:
    • Presynaptic neuron: delivers the signal to the synapse.
    • Postsynaptic neuron: receives the signal.
    • Postsynaptic potential (PSP): the net depolarization or hyperpolarization produced in the postsynaptic neuron.

Inhibitory transmission and modulation

  • Inhibitory synapses (IPSPs):
    • IPSPs cause hyperpolarization of the postsynaptic membrane, moving it further away from the threshold and reducing the likelihood of firing.
    • IPSPs can serve as a “brake” on excitation, allowing fine-tuning of neural circuits.
  • Temporal and spatial interactions:
    • Excitatory and inhibitory inputs can combine in time and space to shape the final output of the postsynaptic neuron.
    • The combination of EPSPs and IPSPs can produce complex, adaptive responses (e.g., reflex modulation).
  • Spontaneous firing and modulation:
    • Neurons have spontaneous firing rates that can be shifted by excitatory or inhibitory inputs.
    • This baseline activity can be modulated to change the likelihood of firing in response to further stimuli.

Variability and complexity of synaptic transmission

  • Synaptic effects are not simply on/off switches:
    • There is large variance in the duration and strength of synaptic effects depending on:
    • The type and amount of neurotransmitter released
    • Receptor types and density on the postsynaptic membrane
    • The combined effect of multiple synapses can be more than or less than additive, depending on molecular interactions.
  • Neurotransmitter types and duration:
    • Different neurotransmitters have different profiles of duration and impact, contributing to the diversity of signaling in the CNS.
  • Conceptual takeaway:
    • The strength and timing of neural signals can be heavily modulated, enabling complex processing and flexible behavior.

Wiring diagrams and network examples

  • Simple wiring concept:
    • An axon projects excitatory synapses onto a postsynaptic cell and also onto an inhibitory interneuron.
    • The inhibitory interneuron also targets the postsynaptic cell, providing inhibition to modulate firing probability.
    • This configuration supports more complex network behavior than a single direct excitatory path.
  • Simple two-input example (a or b):
    • If the postsynaptic neuron (x) has a threshold of 1, stimulation by either input A or input B can cause x to fire if either one alone brings the total to or above the threshold.
    • This illustrates how different inputs can converge to control a single output neuron.

Practical takeaways and real-world relevance

  • Why synaptic complexity matters:
    • Allows for nuanced control of movement, perception, and reflexes beyond a simple one-step transmission.
    • Enables learning and adaptation through synaptic plasticity and modulation by other inputs.
  • Real-world analogy and learning value:
    • Synapses provide a model for how teams and systems balance multiple inputs to produce a coordinated output, mirroring how real-world tasks require integrating diverse signals and collaborating components.
  • Educational design implications from the course context:
    • Group work builds teamwork skills relevant to professional settings, even if some students prefer solitary work.
    • Providing lecture notes, summaries, and access to recordings can help with learning, especially when topics are intricate or controversial.
    • Encouraging questions, including light-hearted or humorous ones, fosters a supportive learning environment.

Quick reference: key numbers and formulas

  • Resting membrane potential: Vrest=−70 mVV_{rest} = -70\ \text{mV}
  • Example EPSP depolarization: from Vrest=−70 mVV_{rest} = -70\ \text{mV} toward −60 mV-60\ \text{mV} (partial depolarization, not yet at threshold)
  • Action potential trigger threshold: VthV_{th} (neuron-dependent value; occurs when the integrated PSP reaches this level at the axon hillock)
  • Axonal conduction speed: vaxon≈40 m/sv_{axon} \approx 40\ \text{m/s}
  • Reflex arc conduction speed: vreflex≈15 m/s  or lessv_{reflex} \approx 15\ \text{m/s}\;\text{or less}
  • Net postsynaptic potential (PSP) concept: V<em>PSP(t)=∑</em>iEPSP<em>i(t)−∑</em>jIPSPj(t)V<em>{PSP}(t) = \sum</em>i EPSP<em>i(t) - \sum</em>j IPSP_j(t)
    • Each PSP decays over time and space after its arrival.
  • Temporal summation description: repeated PSPs over a short interval can summate to reach threshold, even if individual PSPs are subthreshold.
  • Spatial summation description: simultaneous PSPs from multiple inputs can sum to reach threshold.
  • Conceptual takeaway: the combination and timing of EPSPs and IPSPs determine whether an action potential is fired, illustrating the all-or-none nature of the action potential once threshold is reached.

Summary of key takeaways

  • The synapse is a crucial, modulatory junction that converts electrical signaling into chemical signaling to enable inter-neuronal communication.
  • Sherrington’s work established that reflexes involve multiple synapses and modulatory processes, not just rapid single-axon conduction.
  • Neurons employ temporal and spatial summation to integrate excitatory and inhibitory inputs, with the axon hillock acting as the decision point for firing an action potential.
  • Inhibitory inputs provide a regulatory brake, enabling refined control and complex behavior.
  • Synaptic transmission is dynamic and variable, involving diverse neurotransmitters and receptor interactions, which shape the strength and duration of signaling.
  • Course design considerations emphasize collaborative learning, accessible materials, and a supportive environment for asking questions, all of which support mastering complex topics like synaptic physiology.