lecture exam 4: neural communication: synapses, neurotransmitters, and drug effects

The Synapse and Neural Communication

Reflexes and the Discovery of the Synapse

Reflexes are automatic muscular responses to stimuli and have been instrumental in understanding how neurons communicate. The study of reflexes led to the concept of the synapse, the junction where information is transmitted from one neuron to another.

• Reflexes are slower than conduction along an axon, indicating a delay due to synaptic transmission.

• Temporal summation: Repeated weak stimuli over a short period can produce a stronger response than a single stimulus, suggesting that synaptic inputs can accumulate over time.

• Spatial summation: Several weak stimuli at different locations can combine to trigger a nerve impulse, showing that inputs from multiple synapses can be integrated.

• During reflexes, as one set of muscles relaxes, another set becomes excited, indicating coordinated excitatory and inhibitory synaptic activity.

Example: When a dog's foot is pinched, one leg retracts (flexor muscles excited) while the other three extend (inhibitory messages sent), demonstrating the integration of excitatory and inhibitory signals.

Postsynaptic Potentials

• Excitatory postsynaptic potential (EPSP): A graded depolarization that decays over time and space. EPSPs increase the likelihood of an action potential.

• Inhibitory postsynaptic potential (IPSP): A temporary hyperpolarization of the membrane, making the neuron less likely to fire. IPSPs occur when synaptic input opens gates for K+ to leave or Cl- to enter the cell.

• The likelihood of an action potential depends on the ratio of EPSPs to IPSPs at any moment.

• Spontaneous firing rate: Some neurons produce action potentials periodically without synaptic input. EPSPs increase, and IPSPs decrease, this rate.

Chemical Events at the Synapse

Neurotransmitter Synthesis and Release

Neurotransmitters are chemicals that transmit signals across the synaptic cleft. Their synthesis and release depend on their size and type.

• Small neurotransmitters (e.g., acetylcholine) are synthesized in the presynaptic terminal.

• Large neurotransmitters (e.g., peptides) are synthesized in the cell body and transported down the axon.

• Neurotransmitters are synthesized from dietary precursors (e.g., choline for acetylcholine, tryptophan for serotonin).

• Catecholamines (dopamine, norepinephrine, epinephrine) contain a catechol group and an amine group.

Synaptic Transmission

• Transmission across the synaptic cleft is rapid (less than 10 microseconds).

• Most neurons release two or more types of neurotransmitters and can respond to more types than they release.

• Ionotropic effects: Neurotransmitters (e.g., glutamate, acetylcholine) bind to receptors and immediately open ion channels, producing fast, short-lived effects.

• Metabotropic effects: Neurotransmitters bind to receptors that initiate slower, longer-lasting metabolic reactions, often involving G-proteins and second messengers. These effects are important for behaviors like hunger, fear, and anger.

• Neuromodulators: Substances that modulate the activity of other neurotransmitters, often by increasing or decreasing their release or altering postsynaptic responses.

Hormones and the Endocrine System

• Hormones are chemicals secreted by glands and transported by the blood to affect distant organs.

• Endocrine glands produce hormones that trigger long-lasting changes in the body.

• The pituitary gland (attached to the hypothalamus) consists of:

  • Anterior pituitary: Glandular tissue, synthesizes and releases several hormones.

  • Posterior pituitary: Neural tissue, releases hormones (oxytocin, vasopressin) synthesized in the hypothalamus.

• The hypothalamus regulates hormone levels via a negative-feedback system (e.g., TSH-releasing hormone).

Neurotransmitter Inactivation and Reuptake

• Neurotransmitters are removed from the synapse by:

  • Inactivation: Enzymes break down neurotransmitters (e.g., acetylcholine is broken down by acetylcholinesterase).

  • Reuptake: Presynaptic neurons reabsorb neurotransmitters via transporter proteins (e.g., serotonin reuptake).

  • Enzymes like COMT and MAO convert catecholamines into inactive chemicals.

Drugs and the Synapse

Mechanisms of Drug Action

Drugs can alter neural communication by affecting neurotransmitter synthesis, release, reuptake, breakdown, or receptor activity.

• Drugs may:

  • Increase neurotransmitter synthesis

  • Cause vesicles to leak neurotransmitters

  • Increase neurotransmitter release

  • Decrease reuptake

  • Block breakdown into inactive chemicals

  • Directly stimulate or block postsynaptic receptors

• Agonists: Mimic or increase the effects of neurotransmitters.

• Antagonists: Block the effects of neurotransmitters.

• Affinity: The strength with which a drug binds to a receptor.

• Efficacy: The tendency of a drug to activate a receptor.

Drugs and Dopamine Release

• Most abused drugs stimulate dopamine release in the nucleus accumbens, a brain area associated with pleasure.

• Sustained dopamine release inhibits GABAergic neurons, enhancing reward signals.

Categories and Examples of Psychoactive Drugs

Drug Type	Main Action	Examples	Mechanism
Stimulants	Increase excitement, alertness, motor activity, mood	Amphetamines, cocaine, methylphenidate (Ritalin), MDMA (Ecstasy), nicotine	Amphetamines: Increase dopamine release Cocaine: Blocks reuptake of dopamine, norepinephrine, serotonin Methylphenidate: Blocks dopamine reuptake (slower than cocaine) MDMA: Increases dopamine (low dose), serotonin (high dose) Nicotine: Stimulates nicotinic acetylcholine receptors, increases dopamine release
Opiates	Decrease pain, increase relaxation	Morphine, heroin, methadone	Bind to endorphin receptors, inhibit GABA release, increase dopamine Block locus coeruleus (affecting arousal and memory)
Cannabinoids	Analgesia, relaxation, altered perception	THC (marijuana)	Bind to cannabinoid receptors (presynaptic), inhibit glutamate and GABA release Effects: euphoria, altered senses, appetite stimulation, memory impairment
Hallucinogens	Distorted perception	LSD, psilocybin, mescaline	Resemble serotonin, stimulate 5-HT2A receptors

Additional info:

• Chronic use of some drugs (e.g., MDMA) is associated with cognitive deficits, anxiety, and depression.

• Endorphins are endogenous peptides that act as natural painkillers and reinforce certain behaviors by modulating dopamine release.

• The location of cannabinoid receptors in the brain explains the subjective effects of marijuana, such as altered time perception and memory impairment.