L1 - Synaptic Transmission & Beginner Neural Circuit Computations

Recap & Scope

  • Lesson 2: action potentials (“spikes”) move information reliably along one neuron.

  • Lesson 3 (4 videos): how neurons pass information to other neurons; focus on synapses.

  • Today’s video objectives:

    • Distinguish electrical vs. chemical synapses (structure & function).

    • Explain how different patterns of spikes in neuron A translate into activity in neuron B.

    • Show that synaptic connections—and therefore computations—can be modified over time.

Propagation Within vs. Between Neurons

  • Within one neuron:

    • AP initiated at axon hillock propagates to axon terminal nearly unchanged (just delayed).

  • Between neurons (at the synapse): three realistic response patterns were illustrated:

    1. 1 : 1 relay – every incoming AP in A evokes an AP in B.

    2. First-only relay – only the first AP of each burst in A triggers B.

    3. Summation requirement – only when A fires a sufficiently dense burst does B reach threshold.

  • Goal: understand mechanisms that create each scenario and how plasticity can switch between them.

Simple Circuits & Basic Computations

  • Figures ignored dendrites for clarity (one axon terminal ↦ one postsynaptic site).

  • Circuit examples:

    • Single A→B synapse: B’s spike train roughly mirrors A’s.

    • Multiple synapses A→B: stronger influence; B spikes more reliably.

    • A→C→B chain: same logic as A→B but with extra delay and more failure points.

    • Divergence: one A branches to four different downstream neurons – A influences many targets.

    • Convergence (mentioned): many presynaptic neurons converge on one postsynaptic cell.

  • Two-input examples:

    • Summation circuit – Neuron D spikes mainly when both A and B are active (A+B).

    • Subtraction circuit – An excitatory A and inhibitory B both contact D; D spikes when A is active and B is silent (A–B).

Synapse Types Overview

  • Two fundamental categories:

    1. Electrical synapses – direct ionic continuity through gap junctions.

    2. Chemical synapses – presynaptic electrical signal → chemical transmitter → postsynaptic electrical change.

Electrical Synapses (Gap Junctions)

  • Membrane separation: \approx 4\,\text{nm} (bilipid layer itself \approx 3\,\text{nm}).

  • Structure:

    • Each membrane contributes a connexon (hemichannel) made of six connexins.

    • Two opposing connexons align to form a non-selective aqueous pore (passes cations & anions).

  • Functional traits:

    • Bidirectional current flow; either neuron can influence the other.

    • Very fast (virtually no synaptic delay).

    • Postsynaptic potential amplitude much smaller than presynaptic AP (depends on number of gap junctions).

    • Computationally inflexible – cannot easily modulate strength on short time scales; need to add/remove channels for lasting change.

Chemical Synapses

  • Synaptic cleft width: \approx 20{-}40\,\text{nm} (larger than electrical synapse).

  • Unidirectional: information flows presynaptic → postsynaptic only.

  • Presynaptic terminal specializations:

    • Active zones (electron-dense) house proteins that dock & release vesicles.

    • Vesicles (~40–60 nm) contain neurotransmitter; mitochondria supply ATP.

  • Postsynaptic specialization:

    • Postsynaptic density (PSD) packed with receptors, scaffolding proteins, signaling molecules.

  • Slower than electrical synapses but far more versatile (plasticity, excitation vs. inhibition, modulation, etc.).

Five Ways to Classify Chemical Synapses

1 – By Location on Target Neuron

  • Axodendritic

    • Onto dendritic spine or shaft; classic excitatory site.

  • Axosomatic

    • Onto cell body; often inhibitory.

  • Axoaxonic

    • Onto another axon; usually modulatory (alters transmitter release).

2 – By Effector Cell Type

  • Neuron → neuron (CNS information processing).

  • Neuron → muscle (neuromuscular junction; drives contraction).

  • Neuron → gland (triggers secretion: saliva, sweat, hormones).

3 – By Size / Number of Contacts (Strength)

  • Few small boutons = weak, low-reliability influence.

  • Many large boutons with abundant vesicles & multiple active zones = strong, high-fidelity influence.

  • Divergence example: one axon terminal contacts 5 different spines → spreads signal broadly.

4 – By Ultrastructure (Gray’s Type)

  • Gray’s Type I (asymmetric)

    • Large PSD, round vesicles, commonly on spines, usually excitatory (glutamatergic).

  • Gray’s Type II (symmetric)

    • Thin PSD, flattened/oval vesicles, often on shafts or soma, usually inhibitory (GABAergic).

5 – By Neurotransmitter Released

  • Rule of thumb: a single presynaptic neuron releases one principal small-molecule transmitter at its fast synapses; can co-release peptides for slow modulation.

Neurotransmitter Definition (4 Criteria)

  1. Synthesized in presynaptic neuron (often packaged in vesicles).

  2. Produces a consistent, specific action on postsynaptic cell (e.g., opens cation or anion channel).

  3. Exogenous application mimics endogenous effect.

  4. Specific removal mechanism exists (reuptake, enzymatic breakdown, diffusion).

Major Neurotransmitter Classes

  • Amino acids (smallest)

    • Glutamate – opens cation channels → depolarization → excitatory.

    • GABA & Glycine – open \text{Cl}^- channels → hyperpolarization / shunting → inhibitory.

  • Amines (slightly larger)

    • Acetylcholine (neuromuscular junction, autonomic ganglia).

    • Dopamine, Histamine, Noradrenaline, Serotonin (modulatory systems).

  • Peptides (largest)

    • Short amino-acid chains; stored in large dense-core vesicles/secretory granules; long-lasting, hormone-like effects (e.g., neuropeptide Y, substance P).

Excitatory vs. Inhibitory Output Rule

  • A postsynaptic neuron can receive both excitatory and inhibitory inputs.

  • However, most neurons release only one fast transmitter type:

    • Either excitatory (e.g., glutamate) or inhibitory (e.g., GABA).

  • Some neurons co-release a slow peptide transmitter in addition to their main fast transmitter, but they do not mix glutamate & GABA at the same synapse.

Example Circuit to Analyze (Thought Experiment)

  • High-frequency APs in Neuron A → excitatory onto an interneuron.

  • Interneuron excites itself (auto-synapse) and excites an inhibitory neuron.

  • Inhibitory neuron suppresses Interneuron.

  • Task: Predict AP rate evolution in Neuron B (downstream target) as A’s firing rate changes.

    • Hints: auto-excitation sustains interneuron activity; inhibitory feedback provides delayed negative loop; overall could create adaptation or oscillations.

Key Numbers & Terms to Remember

  • Electrical synapse gap: 4\,\text{nm}.

  • Chemical cleft width: 20{-}40\,\text{nm}.

  • Action-potential amplitude: 70{-}80\,\text{mV} above rest.

  • Lipid bilayer thickness: \approx 3\,\text{nm}.

These notes capture all major & minor points, definitions, circuit motifs, numerical references, and conceptual implications discussed in the transcript. They are organized to serve as a standalone study guide on synaptic transmission and basic neural computations.