Neurotransmitters and neurotransmission

Information between neurons is primarily chemical, while information within a single neuron is electrical. The electrical signal (action potential) is converted into a chemical signal (neurotransmitter release) at the synapse, which then influences the electrical activity of the postsynaptic neuron.

Neurotransmission

Neurotransmission is the process by which neurons communicate with each other by transmitting signals across a synapse. It involves the following steps:

1. An action potential arrives at the presynaptic terminal.

2. Depolarization of the presynaptic terminal opens voltage-gated calcium ($Ca^{2+}$) channels.

3. Calcium ($Ca^{2+}$) ions flow into the presynaptic neuron.

4. The influx of $Ca^{2+}$ triggers synaptic vesicles, containing neurotransmitters, to fuse with the presynaptic membrane.

5. Neurotransmitters are released into the synaptic cleft via exocytosis.

6. Neurotransmitters diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic membrane.

7. Binding of neurotransmitters to receptors causes ion channels on the postsynaptic membrane to open, leading to a change in the postsynaptic neuron's membrane potential (either excitation or inhibition).

8. Neurotransmitters are then inactivated through mechanisms such as reuptake, enzymatic degradation, or diffusion away from the synapse, allowing the synapse to be ready for the next signal.

Role of Calcium ($Ca^{2+}$) in Neurotransmission

Calcium ($Ca^{2+}$) ions play a critical role in neurotransmission. When an action potential reaches the presynaptic terminal, it opens voltage-gated $Ca^{2+}$ channels. The subsequent influx of $Ca^{2+}$ into the presynaptic terminal acts as a signal that triggers the fusion of neurotransmitter-containing vesicles with the presynaptic membrane, leading to the release of neurotransmitters into the synaptic cleft. Without $Ca^{2+}$ entry, neurotransmitter release would not occur.

Key Terms in Neurotransmission

• Synapse: The specialized junction between two neurons where information is transmitted from one neuron to another.

• Presynaptic: Refers to the neuron that sends the signal across the synapse, containing the axon terminal from which neurotransmitters are released.

• Postsynaptic: Refers to the neuron that receives the signal across the synapse, containing receptors on its dendrites or cell body.

• Cleft: The narrow space between the presynaptic terminal and the postsynaptic membrane where neurotransmitters are released.

• Vesicle: Small, membrane-bound sacs within the presynaptic terminal that store neurotransmitters.

• Exocytosis: The process by which synaptic vesicles fuse with the presynaptic membrane to release their neurotransmitter content into the synaptic cleft.

• Neurotransmitter: A chemical messenger that transmits signals across a chemical synapse from one neuron to another, or to a target cell (like a muscle cell).

• Receptor: A protein on the postsynaptic membrane (or presynaptic membrane, autoreceptors) that specifically binds to neurotransmitters, initiating a response in the postsynaptic neuron.

• Ion channel: A protein pore in the cell membrane that allows specific ions to pass through, thereby changing the electrical potential across the membrane.

• Reuptake: The process by which neurotransmitters are actively transported back into the presynaptic neuron or glial cells after release, ending their action in the synaptic cleft.

• Enzymatic degradation: The breakdown of neurotransmitters in the synaptic cleft by specific enzymes, rendering them inactive (e.g., acetylcholinesterase breaking down acetylcholine).

• Diffusion: The passive movement of neurotransmitters away from the synaptic cleft into the surrounding extracellular fluid, reducing their concentration at the receptors.

• Excitation: A postsynaptic effect that makes the postsynaptic neuron more likely to generate an action potential (results in an Excitatory Postsynaptic Potential, EPSP).

• Inhibition: A postsynaptic effect that makes the postsynaptic neuron less likely to generate an action potential (results in an Inhibitory Postsynaptic Potential, IPSP).

• Divergence: A neural circuit pattern where the axon of one neuron branches to make synaptic contacts with many other neurons, allowing one signal to affect multiple targets.

• Convergence: A neural circuit pattern where many neurons make synaptic contact with a single neuron, allowing multiple signals to be integrated by one target neuron.

Otto Loewi's Discovery of the First Neurotransmitter

Otto Loewi conducted an experiment in 1921 that provided the first evidence of chemical neurotransmission. He isolated two frog hearts: one with its vagus nerve intact and the other without. He stimulated the vagus nerve of the first heart, which slowed its beat. He then collected the fluid surrounding this heart and applied it to the second heart (without nerve stimulation), which also slowed down. This demonstrated that a chemical substance, dubbed "Vagusstoff" (later identified as Acetylcholine), was released by the stimulated nerve and transferred through the fluid to affect the second heart, proving chemical communication between nerves and organs.

Neurotransmitter vs. Hormone

• Neurotransmitters are chemical messengers that typically act locally and rapidly across the synaptic cleft, affecting specific target neurons or cells. Their effects are usually short-lived and precisely localized.

• Hormones are chemical messengers produced by endocrine glands that are released into the bloodstream and travel throughout the body to act on distant target cells. Their effects are generally slower, longer-lasting, and more widespread.

Seven Main Neurotransmitters

1. Acetylcholine (ACh)

   • Role: Important for muscle contraction (at the neuromuscular junction), learning, memory, and attention in the central nervous system (CNS).

   • Characteristics: Excitatory to skeletal muscles but inhibitory to heart muscles; involved in REM sleep.

2. Dopamine (DA)

   • Role: Key to reward, motivation, pleasure, motor control, and decision-making.

   • Characteristics: Associated with addiction; dysregulation is linked to Parkinson's disease (low DA) and schizophrenia (high DA).

3. Norepinephrine (NE) / Noradrenaline

   • Role: Involved in alertness, arousal, vigilance, mood, and the fight-or-flight response.

   • Characteristics: Both a neurotransmitter and a hormone; released in response to stress and affects heart rate and blood pressure.

4. Serotonin (5-HT)

   • Role: Regulates mood, sleep, appetite, digestion, learning, and memory.

   • Characteristics: Low levels are associated with depression and anxiety; targeted by many antidepressant medications (SSRIs).

5. Gamma-Aminobutyric Acid (GABA)

   • Role: The primary inhibitory neurotransmitter in the CNS.

   • Characteristics: Reduces neuronal excitability, thus having a calming effect; involved in anxiety regulation and sleep; targeted by anxiolytic drugs like benzodiazepines.

6. Glutamate

   • Role: The primary excitatory neurotransmitter in the CNS.

   • Characteristics: Crucial for learning and memory formation (long-term potentiation, LTP); excessive levels can lead to excitotoxicity and neuronal damage (e.g., in stroke).

7. Endorphins

   • Role: Endogenous opioids that act as natural pain relievers and create feelings of euphoria.

   • Characteristics: Released in response to stress, pain, and vigorous exercise ("runner's high"); involved in reward pathways.