Part 5 · Chapter 5.4

Neurotransmitters

Neurotransmitters are chemical messengers released from presynaptic terminals into the synaptic cleft, binding postsynaptic receptors to open or close ion channels (ionotropic) or activate G-protein cascades (metabotropic). This chapter covers the four classical families (amino acids, biogenic amines, acetylcholine, peptides), their synthesis, release via SNARE-mediated exocytosis, and inactivation.

1. Neurotransmitter Families

Amino acids: glutamate (principal excitatory, ~80% CNS synapses), GABA (principal inhibitory), glycine (spinal inhibitory).
Biogenic amines: dopamine (reward, motor), norepinephrine (arousal), serotonin (mood), histamine (wakefulness).
Acetylcholine: NMJ, autonomic ganglia, basal forebrain / brainstem CNS projections.
Peptides: substance P, enkephalins, oxytocin, neuropeptide Y — often co-released with small-molecule transmitters.
Gaseous: NO, CO — diffuse across membranes, retrograde signalling.

2. Synthesis, Storage, Release

Small-molecule transmitters are synthesised in the terminal (e.g., dopamine from tyrosine via TH + DDC). Peptides are synthesised in the cell body and transported in large dense-core vesicles. Packaging uses vesicular transporters (VMAT1/2, VAChT, VGluT) driven by the vesicular H⁺ gradient. Release requires Ca²⁺ influx through P/Q-type Ca²⁺ channels, which triggers SNARE (synaptobrevin + syntaxin + SNAP-25) zippering to fuse the vesicle with the plasma membrane (Jahn & Südhof 1994, Nobel 2013).

Simulation: Cleft Dynamics & PSCs

Python

script.py43 lines

import numpy as np, matplotlib
matplotlib.use('Agg')
import matplotlib.pyplot as plt

# Neurotransmitter cleft transient
t = np.linspace(0, 5, 1000)
# Exocytosis at t=0.5 ms; peak [NT] ~mM in cleft; clearance by diffusion + uptake
release = np.where((t > 0.4) & (t < 0.6), 1.0, 0.0)
NT = np.zeros_like(t)
for i in range(1, len(t)):
    dt = t[i]-t[i-1]
    NT[i] = NT[i-1] + dt*(200*release[i] - 5*NT[i-1])

# Postsynaptic current: AMPA (fast) vs NMDA (slow) vs GABAA (fast Cl)
I_AMPA = 40 * NT * np.exp(-t/0.3)
I_NMDA = 10 * NT.cumsum() * 0.001 * np.exp(-t/100)
I_GABA = -30 * NT * np.exp(-t/0.5)

fig, (ax1, ax2) = plt.subplots(1, 2, figsize=(14, 5), facecolor='#0a0f1e')
for ax in (ax1, ax2):
    ax.set_facecolor('#111e2f'); ax.tick_params(colors='#bae6fd')
    for s in ax.spines.values(): s.set_color('#334155')
    ax.grid(True, color='#334155', alpha=0.3)

ax1.plot(t, NT, color='#fbbf24', lw=2.5)
ax1.set_xlabel('Time (ms)', color='#bae6fd')
ax1.set_ylabel('[NT] in cleft (rel)', color='#bae6fd')
ax1.set_title('Cleft transient: peak mM, clearance <1 ms',
              color='#67e8f9', fontweight='bold')

ax2.plot(t, I_AMPA, color='#34d399', lw=2.5, label='AMPA')
ax2.plot(t, I_NMDA*20, color='#f472b6', lw=2.5, label='NMDA x20')
ax2.plot(t, I_GABA, color='#60a5fa', lw=2.5, label='GABA-A')
ax2.set_xlabel('Time (ms)', color='#bae6fd')
ax2.set_ylabel('Postsynaptic current (pA)', color='#bae6fd')
ax2.set_title('EPSCs (AMPA, NMDA) vs IPSC (GABA-A)',
              color='#67e8f9', fontweight='bold')
ax2.legend(facecolor='#1e293b', edgecolor='#334155', labelcolor='#cbd5e1')

plt.tight_layout()
plt.savefig('output.png', dpi=120, bbox_inches='tight', facecolor='#0a0f1e')
print('Synaptic cleft: ~20 nm, NT diffuses in <1 ms')
print('AMPA: fast EPSC (tau ~2 ms); NMDA: slow, Mg-blocked at rest, Ca-permeable')

Click Run to execute the Python code

Code will be executed with Python 3 on the server

3. Inactivation

Transmitter signal is terminated by: (a) enzymatic degradation (ACh by AChE at NMJ), (b) reuptake via plasma-membrane transporters (DAT, SERT, NET, EAAT glutamate transporters), (c) diffusion + glial uptake, (d) endocytic recycling of vesicles (“kiss-and-run” or full collapse). SSRIs, SNRIs, cocaine, amphetamine all act on monoamine transporters.

Key References

• Südhof, T. C. (2013). “Neurotransmitter release: the last millisecond in the life of a synaptic vesicle.” Neuron, 80, 675–690.

• Purves, D. et al. (2018). Neuroscience, 6th ed. Sinauer.

• Edwards, R. H. (2007). “The neurotransmitter cycle and quantal size.” Neuron, 55, 835–858.

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