Neurotransmission:

1. Introduction to Neurotransmission

• The human brain has approximately 100 billion neurons.

• Neurons communicate within and between each other.

• Communication happens through synaptic transmission.

• Two types of synapses: electrical and chemical.

2. Structure of a Neuron

Main Components:

1. Dendrites – Receive information from other neurons (like antennas).

2. Soma (Cell Body) – Processes information.

3. Axon – Sends information as an electrical signal (action potential).

4. Axon Terminals (Terminal Boutons) – Release neurotransmitters to communicate with other neurons.

Neuronal Membrane:

• Separates intracellular (inside the cell) and extracellular (outside the cell) environments.

• Composed of a lipid bilayer with protein structures that control what enters and exits.

3. The Synapse (Neuron-to-Neuron Communication)

Types of Synapses

1. Electrical Synapses (Rare in adult mammals):

   • Found in the retina.

   • Neurons connected directly via gap junctions (small channels).

   • Ions move freely between cells.

   • Very fast transmission.

2. Chemical Synapses (Common in the brain):

   • Neurons communicate by releasing neurotransmitters.

   • Involves a small gap called the synaptic cleft.

   • Slower but more versatile.

4. Steps of Chemical Neurotransmission

1. Neurotransmitter Synthesis – Neurotransmitters are made in the neuron.

2. Storage – Stored in vesicles in the axon terminal.

3. Action Potential – An electrical signal travels down the axon.

4. Calcium (Ca²⁺) Channels Open – Voltage-gated calcium channels let Ca²⁺ into the neuron.

5. Vesicle Movement & Docking – Vesicles move to the membrane and get ready to release neurotransmitters.

6. Exocytosis – Neurotransmitters are released into the synaptic cleft.

7. Neurotransmitter Binding – Neurotransmitters bind to receptors on the next neuron.

8. Neurotransmitter Inactivation – Neurotransmitters are removed by:

   • Reuptake – Taken back into the neuron.

   • Enzyme Breakdown – Broken down by enzymes.

   • Diffusion – Move away from the synapse.

5. Neurotransmitters & Their Functions

A. Excitatory vs. Inhibitory Neurotransmitters

• Excitatory → Increases likelihood of firing (e.g., Glutamate).

• Inhibitory → Decreases likelihood of firing (e.g., GABA).

B. Types of Neurotransmitters

6. Neurotransmitter Receptors

A. Ionotropic Receptors (Fast-Acting)

• Directly open ion channels.

• Cause an immediate change in neuron activity.

• Example:

  • Glutamate Receptors (Excitatory) → Allow Na⁺ into the neuron → Depolarization (EPSP).

  • GABA Receptors (Inhibitory) → Allow Cl⁻ into the neuron → Hyperpolarization (IPSP).

B. Metabotropic Receptors (Slow & Amplified Response)

• Work through G-proteins and second messengers.

• Cause slower but more complex effects.

• Example:

  • GABA B Receptor (Inhibitory).

  • Dopamine & Serotonin Receptors.

AMPA Receptors

• Primary function: Rapid excitatory neurotransmission.

• Activation:

  • When glutamate binds, the channel immediately opens, allowing Na⁺ to enter and K⁺ to leave.

  • This leads to depolarization and an excitatory postsynaptic potential (EPSP).

• Role in synaptic transmission:

  • AMPA receptors mediate fast transmission in the central nervous system.

  • Their quick kinetics make them crucial for rapid signaling.

NMDA Receptors

• Primary function: Synaptic plasticity, learning, and memory.

• Activation:

  • Binding of glutamate alone is not enough.

  • At resting membrane potential (-65 mV), Mg²⁺ blocks the NMDA receptor channel.

  • When the neuron is depolarized (e.g., by AMPA receptor activation), Mg²⁺ is removed, allowing ions to pass.

• Ion selectivity: Unlike AMPA, NMDA receptors allow Ca²⁺ influx, which plays a major role in LTP (long-term potentiation).

• Role in synaptic transmission:

  • NMDA receptors help in strengthening synapses (important for learning and memory).

  • Since NMDA receptors remain open longer, they contribute to prolonged excitatory effects.

Differences between AMPA & NMDA:

Similarities of AMPA & NMDA:

7. Specific Neurotransmitters & Their Pathways

A. Glutamate (Excitatory)

• Main excitatory neurotransmitter in the CNS.

• Activates AMPA, NMDA, and Kainate receptors.

• Excessive glutamate can lead to excitotoxicity, causing brain damage (e.g., stroke, chronic stress).

B. GABA (Inhibitory)

• Main inhibitory neurotransmitter.

• GABA A Receptors (Ionotropic) → Open Cl⁻ channels (Fast inhibition).

• GABA B Receptors (Metabotropic) → Work via G-proteins (Slow inhibition).

• Drugs that increase GABA include:

  • Benzodiazepines (Valium, Xanax) – Reduce anxiety.

  • Alcohol – Enhances inhibition.

  • Barbiturates – Used for sedation.

C. Dopamine (Reward & Movement)

• Found in three main pathways:

  1. Nigrostriatal System – Movement control (Parkinson’s disease).

  2. Mesolimbic System – Reward & addiction (Drugs increase dopamine here).

  3. Mesocortical System – Cognition & emotion (Schizophrenia-related).

• Drugs affecting dopamine:

• Cocaine & Amphetamines → Block dopamine reuptake (stimulant effects).

• L-DOPA → Increases dopamine in Parkinson’s patients.

D. Serotonin (Mood & Emotion)

• Found in the Raphe nuclei of the brainstem.

• Functions in:

  • Mood & depression.

  • Sleep & appetite.

  • Pain perception.

• Drugs affecting serotonin:

  • SSRIs (e.g., Prozac) → Block serotonin reuptake (antidepressant).

  • MDMA (Ecstasy) → Releases more serotonin (euphoria, empathy)

8. Drug Effects on Neurotransmission

Key Takeaways