How Neurons Communicate and Adapt: A Comprehensive Study Guide

How Neurons Communicate and Adapt

Introduction to Brain and Behavior (Bryan Kolb, Ian Q. Whishaw, G. Campbell Teskey – Seventh Edition)

  • This chapter explores the mechanisms of neuronal communication and adaptation.

  • Key topics include:

    • Chemical messages within the brain.

    • Variety of neurotransmitters and receptors.

    • Neurotransmitter systems and their influence on behavior.

    • Adaptive role of synapses in learning and memory.

A Chemical Message: Early Discoveries

  • Otto Loewi (1921) and the Frog Heart Experiment:

    • First isolation of a chemical messenger.

    • Loewi demonstrated that the vagus nerve in a frog heart contains a chemical that slows its rate.

    • He subsequently identified two messenger chemicals: one for speeding up heart rate (excitatory) and one for slowing it down (inhibitory).

    • This experiment laid the foundation for understanding chemical synaptic transmission.

  • Acetylcholine (ACh):

    • The first neurotransmitter discovered in both the peripheral nervous system (PNS) and central nervous system (CNS).

    • Activates skeletal muscles in the somatic nervous system (SNS).

    • Can excite or inhibit internal organs in the autonomic nervous system (ANS).

  • Research Focus 5-1: The Basis of Neural Communication in a Heartbeat:

    • Heart rate adjusts to match energy expenditure and the body's needs for nutrients and oxygen.

    • Loewi's work showed a chemical signal from the vagus nerve mediating heart rate changes.

  • Experiment 5-1: How Does a Neuron Pass on a Message? (Conceptual experiment involving direct chemical transfer, building on Loewi's insights).

  • Loewi’s Complementary Experiments:

    • Epinephrine (EP, or adrenaline): A chemical messenger that acts as both a hormone (mobilizing the body for fight or flight during stress) and a neurotransmitter (in the CNS).

    • Norepinephrine (NE, or noradrenaline): A neurotransmitter found in the brain and the parasympathetic division of the autonomic nervous system; it accelerates heart rate in mammals.

Neurotransmitters: Definition and Discovery

  • Neurotransmitter: A chemical released by a neuron onto a target cell (another neuron, muscle, or gland) with either an excitatory or inhibitory effect.

  • Many of these chemicals also circulate in the bloodstream as hormones, which have distant targets and a slower action than neurotransmitters.

  • Loewi's discoveries spurred the search for more neurotransmitters and their functions.

  • Currently, over 6060 neurotransmitters are confirmed, with up to 200200 posited.

Structure of Synapses

  • The discovery of the electron microscope in the 19501950s (about 3030 years after Loewi's work) facilitated the understanding of synaptic structure.

  • It revealed that neurotransmitters are packaged in vesicles at the axon terminals.

  • Chemical Synapse: A specialized junction where messenger molecules (neurotransmitters) are released from one neuron to excite or inhibit the next neuron.

    • Most synapses in the mammalian nervous system are chemical.

  • Clinical Focus 5-2: Parkinson Disease:

    • Named by Jean-Martin Charcot over 5050 years after James Parkinson's initial descriptions.

    • Neural basis involves:

      • Degeneration of the substantia nigra on the side opposite to symptom manifestation.

      • Symptoms appear when dopamine (DA) levels in the basal ganglia are reduced to less than 10%10\% of normal.

      • Studies in rats confirmed that selective destruction of dopamine-containing neurons produced Parkinsonian symptoms, highlighting dopamine's role in a pathway connecting the substantia nigra to the basal ganglia.

  • Terms to Learn: Structure of Chemical Synapses:

    • Presynaptic membrane (axon terminal): The transmitting side of the synapse.

    • Postsynaptic membrane (dendritic spine): The receiving side of the synapse, often on a dendritic spine.

    • Synaptic cleft: The space between the presynaptic and postsynaptic membranes.

    • Tripartite synapse: The functional integration of the presynaptic terminal, postsynaptic spine, and surrounding astrocyte.

    • Synaptic vesicle (presynaptic): Small sacs containing neurotransmitters in the presynaptic terminal.

    • Storage granule (presynaptic): Larger packages of neurotransmitters, often peptides.

    • Postsynaptic receptor (postsynaptic): Protein molecules on the postsynaptic membrane that bind to neurotransmitters.

    • Anterograde synaptic transmission: The conventional direction of signal transmission, from presynaptic to postsynaptic neuron.

    • Transporter: Protein molecules embedded in the cell membrane that pump building blocks for neurotransmitter synthesis into the cell or reuptake neurotransmitters from the synaptic cleft.

Neurotransmission in Five Steps (Anterograde Synaptic Transmission)

This is a five-step process for transmitting information across a chemical synapse:

  1. Neurotransmitter Synthesis: The neurotransmitter is synthesized inside the neuron.

  2. Neurotransmitter Packaging and Storage: It is packaged and stored within vesicles at the axon terminal.

  3. Neurotransmitter Release: It is transported to the presynaptic membrane and released into the synaptic cleft in response to an action potential.

  4. Receptor-Site Activation: It binds to and activates receptors on the postsynaptic membrane.

  5. Neurotransmitter Inactivation: It is degraded or removed from the synaptic cleft to prevent continuous receptor interaction.

Steps 1 and 2: Neurotransmitter Synthesis, Packaging, and Storage

  • Neurotransmitters are synthesized in two main ways:

    • In the axon terminal: Building blocks from food are pumped into the cell via transporters. This applies to small-molecule transmitters.

    • In the cell body: According to instructions in the DNA (for peptide transmitters), then transported on microtubules to the axon terminal.

  • Origins of neurotransmitters can include different chemical classes: Peptide, Lipid, Gaseous, Ion.

Step 3: Neurotransmitter Release

  • When an action potential arrives at the axon terminal, it opens voltage-sensitive calcium (Ca2+Ca^{2+}) channels.

  • Ca2+Ca^{2+} ions enter the terminal and bind to the protein calmodulin, forming a complex.

  • This complex causes some vesicles to undergo exocytosis (emptying their contents into the synapse) and others to prepare for release.

Step 4: Receptor-Site Activation

  • After release, the neurotransmitter diffuses across the synaptic cleft and binds to transmitter-activated receptors on the postsynaptic membrane.

  • Quantum (pl. quanta): The fixed amount of neurotransmitter contained within each synaptic vesicle, representing the fundamental unit of neurotransmitter release.

  • Receptors can be of different types:

    • Ionotropic receptor: Direct and rapid action.

    • Metabotropic receptor: Indirect and slower action, often involving second messengers.

    • Autoreceptor: A receptor on the presynaptic membrane that detects the amount of neurotransmitter remaining in the cleft and regulates further release.

Step 5: Neurotransmitter Inactivation

To ensure precise and controlled communication, neurotransmitters are quickly removed from the receptor sites and synaptic cleft through at least four ways:

  1. Diffusion: Neurotransmitter diffuses away from the synaptic cleft.

  2. Degradation: Enzymes break down the neurotransmitter (e.g., acetylcholinesterase (AChE) breaks down ACh).

  3. Reuptake: Neurotransmitters are reabsorbed into the presynaptic terminal by transporters.

  4. Astrocyte uptake: Astrocytes (a type of glial cell) absorb neurotransmitters from the cleft.

The Versatile Synapse

  • Synapses vary widely in location, structure, function, and target, forming a versatile chemical delivery system.

  • Connections to dendrites, cell body, or axon allow transmitters to control neuron actions in diverse ways.

Electrical Synapses

  • Gap junction: A specialized connection between cells that allows for direct electrical communication.

    • Contain connexin proteins on adjacent cell membranes that form hemichannels.

    • These hemichannels connect to allow ions (and thus electrical signals) to pass directly between neurons.

    • They act as regulated gates, capable of being open or closed.

    • Eliminate brief delays in information flow typical of chemical synapses.

    • Allow glial cells and neurons to exchange functions and selectively pass specific size molecules.

    • Can facilitate dual chemical and electrical synaptic transmission (mixed synapse), offering greater flexibility.

Excitatory and Inhibitory Messages

Synapses have distinct structural characteristics depending on whether they are excitatory or inhibitory:

  • Excitatory Synapse:

    • Typically located on dendrites.

    • Round vesicles.

    • Dense material on membranes.

    • Wide synaptic cleft.

    • Large active zone.

  • Inhibitory Synapse:

    • Typically located on the cell body.

    • Flat vesicles.

    • Sparse material on membranes.

    • Narrow synaptic cleft.

    • Small active zone.

  • Research Focus 5-3: Dendritic Spines; Small but Mighty:

    • Dendritic spines mediate learning; each spine can act independently and undergo unique changes.

    • They provide the structural basis for behavior, skills, and memories.

    • Impairments in spine formation are linked to some mental disabilities, and spine loss is associated with Alzheimer disease dementia.

Evolution of Complex Neurotransmission Systems

  • Chemical transmission may have evolutionary roots in the feeding behavior of single-celled organisms.

    • Digestive juices are secreted onto prey via exocytosis (similar to neurotransmitter release).

    • Prey is captured via endocytosis.

    • This parallels the release of neurotransmitters for inter-neuronal communication in more complex creatures.

Varieties of Neurotransmitters and Receptors

  • Current research highlights the impressive variety of neurotransmitters and receptors in the human brain.

  • Neurotransmitters operate in versatile ways:

    • Some can be excitatory at one location and inhibitory at another.

    • Two or more neurotransmitters may co-exist and team up in a single synapse, allowing one to potentiate the other.

    • Each neurotransmitter can interact with several receptor subtypes, each having slightly different functions.

  • Identification of New CNS Neurotransmitters: Techniques involve:

    • Staining: Identifying specific chemicals in living tissue.

    • Stimulating: Using microelectrodes on specific neuronal targets to observe responses.

    • Collecting: Preserving nervous system tissue in a saline bath to detect and analyze neuronal communication.

  • Renshaw Loop:

    • Motor-neuron axons leaving the spinal cord use acetylcholine (ACh).

    • Each axon has an axon collateral within the spinal cord that synapses on a nearby CNS interneuron.

    • This interneuron, in turn, synapses back on the motor neuron's cell body, providing feedback.

    • Blocking this loop, e.g., with strychnine toxin, leads to motor neuron overactivity, convulsions, and potentially death from respiratory failure.

  • Broadening the Term Neurotransmitter Today: Beyond simply influencing postsynaptic voltage, neurotransmitters are chemicals that also:

    • Change the structure of a synapse.

    • Communicate via retrograde (reverse direction) messages, influencing the release or reuptake of transmitters on the presynaptic side.

Classes of Neurotransmitters

Neurotransmitters are classified into groups based on their chemical composition:

Small-Molecule Transmitters

  • Quick-acting neurotransmitters synthesized in the axon terminal from dietary nutrients.

  • Packaged into synaptic vesicles ready for use.

  • Best-Known and Well-Studied Small-Molecule Neurotransmitters (Table 5-1 summary):

    • Acetylcholine (ACh)

    • Amines: Dopamine (DA), Norepinephrine (NE, or noradrenaline [NA]), Epinephrine (EP, or adrenaline), Serotonin (5-HT)

    • Amino acids: Glutamate (Glu), Gamma-aminobutyric acid (GABA), Glycine (Gly), Histamine (H)

    • Purines: Adenosine, Adenosine triphosphate (ATP)

Acetylcholine Synthesis

  • Two enzymes combine choline (from diet) and acetate within the cell to synthesize ACh.

  • Acetylcholinesterase (AChE): An enzyme that breaks down ACh in the synapse for reuptake, preventing prolonged action.

Amine Synthesis

  • Involves sequential biochemical modifications, with a different enzyme at each step.

  • Tyrosine: The precursor chemical.

  • Tyrosine hydroxylase: Converts tyrosine into L-dopa (a rate-limiting factor).

  • L-dopa is then converted into dopamine, then norepinephrine, and finally epinephrine.

  • Histamine (H): Another amine neurotransmitter.

Serotonin Synthesis

  • Serotonin (5-HT, or 5-hydroxytryptamine): An amine transmitter synthesized from the amino acid L-tryptophan (found in foods like pork, turkey, milk, bananas).

  • Plays roles in mood regulation, aggression, appetite, arousal, respiration, and pain perception.

Amino Acid Synthesis

  • Considered the