Chapter 2 Synapses

Synapses

Introduction

Neurons communicate via chemical transmission at junctions called synapses. Charles Scott Sherrington coined the term in 1906 to describe the specialized gap between neurons. Sherrington studied reflexes (automatic muscular responses to stimuli) in a reflex arc to understand neuronal communication.

Sherrington's Evidence for Synaptic Delay

Synaptic transmission in the spinal cord is slower than axonal transmission. The speed of conduction along an axon is approximately 40 m/s. The speed of conduction through a reflex arc is slower and more variable (sometimes 15 m/s or less), with the delay occurring at the synapse.

Excitatory Postsynaptic Potential (EPSP)

• Presynaptic neuron: neuron that delivers the synaptic transmission.
• Postsynaptic neuron: neuron that receives the message.
• Excitatory postsynaptic potential (EPSP): graded depolarization that decays over time and space.
• Cumulative effect of EPSPs underlies temporal and spatial summation.

Temporal Summation

Sherrington observed that repeated stimuli over a short period produce a stronger response, illustrating temporal summation. Repeated stimuli can have a cumulative effect, generating a nerve impulse even when a single stimulus is too weak. Temporal summation involves the summation of EPSPs or IPSPs due to repeated stimulation by one neuron.

Spatial Summation

Sherrington also noted that several small stimuli in a similar location could trigger a reflex when a single stimulus could not, illustrating spatial summation. Synaptic input from multiple locations can have a cumulative effect and trigger a nerve impulse.

Spatial Summation Importance

Spatial summation is critical for brain function. Neurons receive numerous incoming axons that often produce synchronized responses. Temporal and spatial summation usually occur together. The sequence of axon firing influences the results.

Recordings from a Postsynaptic Neuron During Synaptic Activation

Illustrates EPSP, temporal summation (several impulses from one neuron over time), spatial summation (impulses from several neurons at the same time), and action potential.

Inhibitory Synapses

Sherrington observed that when a dog's leg was pinched, one leg retracted while the other three extended. This suggested an interneuron in the spinal cord sent an excitatory message to the flexor muscles of one leg and an inhibitory message to the other three legs.

Inhibitory Postsynaptic Potential (IPSP)

Inhibitory postsynaptic potential (IPSP): temporary hyperpolarization of a membrane.

Occurs when synaptic input opens gates for positively charged potassium ions to leave the cell or negatively charged chloride ions to enter the cell.

Serves as an active "brake" that suppresses excitation.

Sherrington's Inference of Inhibitory Synapses

Diagram illustrating sensory neuron, brain neuron, intrinsic neuron, motor neuron axon to extensor muscle and to flexor muscle including excitatory and inhibitory synapses.

A Possible Wiring Diagram for Synapses

Wiring diagram for an "A or B" response including axon and dendrite.

Knowledge Check

• Temporal summation is summation over time. Spatial summation is summation over space.

Nerves Send Messages by Releasing Chemicals

German physiologist Otto Loewi demonstrated that synaptic communication is chemical. Stimulation of one nerve slowed the heart, while another increased it, indicating that chemicals, not electricity, were responsible. Loewi stimulated the vagus nerve of one frog’s heart, decreasing the heartbeat, and transferring fluid from that heart to another frog’s heart, he observed a decrease in its heartbeat.

Transmission at a Synapse

Diagram explaining:

1. Synthesis of smaller neurotransmitters (e.g., acetylcholine).
2. Action potential causes calcium to enter, releasing neurotransmitter.
3. Neurotransmitter binds to receptor.
4. Separation from receptors.
5. Reuptake of neurotransmitter by transporter protein.
6. Postsynaptic cell releases retrograde transmitters that slow further release from presynaptic cell.
7. Negative feedback sites respond to retrograde transmitter or to presynaptic cell's own transmitter.

The Chemical Events at the Synapse

Major sequence of events allowing communication between neurons across the synapse:

1. Neuron synthesizes neurotransmitters.
2. Action potentials travel down the axon.
3. Released molecules diffuse across the cleft, attach to receptors, and alter postsynaptic neuron activity.
4. Neurotransmitter molecules separate from their receptors.
5. Neurotransmitters are taken back into the presynaptic neuron for recycling or diffuse away.
6. Postsynaptic cells may send reverse messages to slow the release of further neurotransmitters by presynaptic cells.

Types of Neurotransmitters

• Amino Acids: glutamate, GABA, glycine, aspartate.
• Modified Amino Acid: acetylcholine.
• Monoamines: serotonin, dopamine, norepinephrine, epinephrine.
• Neuropeptides: endorphins, substance P, neuropeptide Y.
• Purines: ATP, adenosine.
• Gases: NO (nitric oxide).

Synthesis of Transmitters

Neurons synthesize neurotransmitters and other chemicals from dietary substances.

• Acetylcholine is synthesized from choline found in milk, eggs, and nuts.
• Tryptophan is a precursor for serotonin.
• Catecholamines (epinephrine, norepinephrine, and dopamine) contain a catechol group and an amine group.

Anatomy of a Synapse

Diagram illustrating the anatomy of a synapse.

Effects on the Postsynaptic Cell

The effect of a neurotransmitter depends on its receptor on the postsynaptic cell. Transmitter-gated or ligand-gated channels are controlled by a neurotransmitter. A ligand is a chemical that binds to something.

Ionotropic Effects

Occur when a neurotransmitter attaches to receptors and immediately opens ion channels.

• Effects occur rapidly (less than a millisecond) and are short-lasting.
• Rely on glutamate or GABA.

Metabotropic Effects and Second Messenger Systems

Occur when neurotransmitters attach to a receptor and initiate longer lasting metabolic reactions. The chemicals that affect these receptors are called neuromodulators. Metabotropic synapses use chemicals like dopamine, norepinephrine, serotonin, and sometimes glutamate and GABA.

Metabotropic Effects and Second Messenger Systems Details

When a neurotransmitter attaches to a metabotropic receptor, it bends the receptor protein that goes through the cell membrane, allowing the protein inside the neuron to react with other molecules. Metabotropic events include taste, smell, and pain. Metabotropic effects are also important for arousal, attention, hunger, thirst, and emotion.

Sequence of Events at a Metabotropic Synapse

Diagram:

1. Transmitter molecule attaches to receptor.
2. Receptor bends, releasing G protein.
3. G protein activates a "second messenger" such as cyclic AMP, which alters a metabolic pathway, turns on a gene in the nucleus, or opens or closes an ion channel.

G-Proteins

G-protein activation is coupled to guanosine triphosphate (GTP), an energy-storing molecule, which increases the concentration of a “second-messenger.” The second messenger communicates to areas within the cell and may open or close ion channels, alter production of activating proteins, or activate chromosomes.

Drugs That Bind to Receptors

Hallucinogenic drugs distort perception and chemically resemble serotonin (e.g., LSD). They stimulate serotonin type 2A receptors (5-HT2A) at inappropriate times or for longer durations. Opiates attach to specific receptors in the brain. The brain produces neuropeptides known as endorphins. Opiate drugs exert their effects by binding to the same receptors as endorphins.

Inactivation and Reuptake of Neurotransmitters

Neurotransmitters released into the synapse are subject to either inactivation or reuptake. During reuptake, the presynaptic neuron takes up most of the neurotransmitter molecules intact and reuses them. Transporters are special membrane proteins that facilitate reuptake.

Inactivation and Reuptake of Neurotransmitters - Examples

• Serotonin is taken back up into the presynaptic terminal.
• Acetylcholine is broken down by acetylcholinesterase into acetate and choline.
• Enzymes break down any transmitter molecules that the transporters do not reuptake.

Stimulant Drugs

• Amphetamine and cocaine:
  • Stimulate dopamine synapses by increasing the release of dopamine from the presynaptic terminal.
• Methylphenidate (Ritalin):
  • Blocks the reuptake of dopamine but in a more gradual and controlled rate.
  • Often prescribed for people with ADHD.

Negative Feedback from the Postsynaptic Cell

Negative feedback in the brain is accomplished in two ways:

• Autoreceptors: receptors that detect the amount of transmitter released and inhibit further synthesis and release.
• Postsynaptic neurons: respond to stimulation by releasing chemicals that travel back to the presynaptic terminal where they inhibit further release.

Cannabinoids

The active chemicals in marijuana bind to anandamide or 2-AG receptors on presynaptic neurons or GABA neurons. When cannabinoids attach to these receptors, the presynaptic cell stops sending, decreasing both excitatory and inhibitory messages from many neurons and typically resulting in decreased anxiety.

Electrical Synapses

A few special-purpose synapses operate electrically and are faster than all chemical transmissions.

• Gap junction: direct contact of the membrane of one neuron with the membrane of another.
• Depolarization occurs in both cells, resulting in the two neurons acting as if they were one.

Hormones

Chemicals secreted by a gland or other cells that are transported to other organs by the blood where it alters activity.

• Produced by endocrine glands.
• Important for triggering long-lasting changes in multiple parts of the body.

Selective List of Hormones

Table including the following:

• Hypothalamus: Various releasing hormones (Promote/inhibit release of hormones from pituitary)
• Anterior pituitary: Thyroid-stimulating hormone(Stimulates thyroid gland), Luteinizing hormone (Stimulates ovulation), Follicle-stimulating hormone (Promotes ovum maturation (female), sperm production (male)), ACTH (Increases steroid hormone production by adrenal gland), Prolactin (Increases milk production), Growth hormone (Increases body growth)
• Posterior pituitary: Oxytocin (Uterine contractions, milk release, sexual pleasure), Vasopressin (Raises blood pressure, decreases urine volume)
• Pineal: Melatonin (Sleepiness; also role in puberty)
• Adrenal cortex: Aldosterone (Reduces release of salt in the urine), Cortisol (Elevated blood sugar and metabolism)
• Adrenal medulla: Epinephrine, norepinephrine (Similar to actions of sympathetic nervous system)
• Pancreas: Insulin (Helps glucose enter cells), Glucagon (Helps convert stored glycogen into blood glucose)
• Ovary: Estrogens and progesterone (Female sexual characteristics and pregnancy)
• Testis: Testosterone (Male sexual characteristics and pubic hair)
• Kidney: Renin (Regulates blood pressure, contributes to hypovolemic thirst)
• Fat cells: Leptin (Decreases appetite, increases activity)

The Pituitary Gland and the Hypothalamus

Attached to the hypothalamus and consists of two distinct glands:

• Anterior pituitary: composed of glandular tissue
  • Hypothalamus secretes releasing and inhibiting hormones that control anterior pituitary.
• Posterior pituitary: composed of neural tissue
  • Hypothalamus produces oxytocin and vasopressin, which the posterior pituitary releases in response to neural signals.

Pituitary Hormones

Diagram with Anterior pituitary (GH, ACTH, TSH, FSH, LH, and prolactin) and Posterior pituitary (Vasopressin and oxytocin).

Negative Feedback in the Control of Thyroid Hormones

Diagram showing Hypothalamus (TSH-releasing hormone), Anterior pituitary (TSH), and Thyroid gland (Thyroxine and triiodothyronine).

Discussion

• If serotonin axons were destroyed, LSD would still have its full effects. However, if dopamine axons were destroyed, amphetamine and cocaine would lose their effects. Discuss how this difference exists.
• Keep notes and share your group’s thoughts with the large group.

Study Questions

• How did Charles Sherrington use behavioral observations to infer the major properties of synapses?
• How do EPSPs (excitatory postsynaptic potentials) and IPSPs (inhibitory postsynaptic potentials) contribute to temporal and spatial summation?
• Why is inhibition important in the functioning of the nervous system?
• What is the sequence of events at a synapse, starting from the synthesis of neurotransmitters, to the stimulation of receptors, and the final disposition of the transmitter molecules?
• What is the difference between ionotropic and metabotropic receptors, and how does each type function?
• How do certain drugs affect behavior through their actions at synapses?
• What are some common hormones, and what effects do they have on the body or behavior?