neurotransmitters

NEUROTRANSMITTERS

Chapter 3

Introduction
  • Cell Phones: Reminder to turn off during the lecture.
  • Attendance Sheet: Instructions to sign.
Learning Objectives
  • Chemicals of Consequence: An overview of significant neurotransmitters and their roles.
  • Opioids: Explanation of why opioids are challenging to quit without therapeutic drugs.
  • THC Mimicry: Exploration of the blissful chemical that THC mimics, impacting the brain's pleasure pathways.

SYNAPSE

  • Definition: The synapse is the physical space between neurons.

NEUROTRANSMITTERS

  • Definition: Chemicals that transmit signals between neurons.
  • Effects: Can induce either an excitatory or inhibitory effect on a target neuron.
  • Otto Loewi's Experiment: Demonstrated the chemical transmission of neurotransmitters using acetylcholine as a prime example.

SYNAPSE MECHANICS

  • Voltage-Gated Calcium Channels: These channels open in response to changes in voltage and allow Ca2+ ions to enter the neuron.
  • Ca2+ Influx: The increase in intracellular calcium concentration triggers neurotransmitter release through exocytosis.
  • Neurotransmitter Release: The process by which neurotransmitters are expelled from the presynaptic neuron into the synaptic cleft.
  • Postsynaptic Receptors: Neurotransmitters bind to these receptors on the postsynaptic neuron.
  • Reuptake: The process by which neurotransmitters are reabsorbed by the presynaptic neuron.
  • Excitatory Postsynaptic Potential (EPSP): A depolarization of the postsynaptic membrane that makes the neuron more likely to fire an action potential.
  • Inhibitory Postsynaptic Potential (IPSP): A hyperpolarization of the postsynaptic membrane that makes the neuron less likely to fire an action potential.

MULTIPLE NEUROTRANSMITTERS

  • Co-Transmitters: More than one neurotransmitter can be present at a nerve terminal.
    • Vesicle Packaging: Each neurotransmitter is typically packaged in separate vesicles, with some exceptions emerging.
    • Frequency of Action Potential:
    • Low-Frequency Action Potential: May typically release only one type of neurotransmitter, which is usually a small molecule.
    • High-Frequency Action Potential: Can release multiple types, often involving neuropeptides, which are larger molecules.

NEUROPEPTIDES

  • Features: Neuropeptides can be in large vesicles alongside classic neurotransmitters.
  • Precursor Requirement: They are derived from protein molecules that must be synthesized in the cell body, packaged, and transported to axon terminals.
  • Replenishment: Compared to other neurotransmitters, neuropeptides have slower replenishment rates.

RETROGRADE NEUROTRANSMITTERS

  • Types: Lipid and gas neurotransmitters that are not released from vesicles. These are typically produced in the postsynaptic cell.
    • Lipid Example: Anandamide, which reduces the amount of neurotransmitter released.
    • Gas Example: Nitric oxide, which has various signaling roles in the brain.

CONTROLLING NEUROTRANSMITTER RELEASE

  • Autoreceptors: Located on the terminal of the presynaptic neuron, activated by the neurotransmitter itself, leading to the inhibition of further neurotransmitter release.

DRUG ACTIONS ON NEUROTRANSMITTERS

  1. Drug serves as a neurotransmitter precursor.
  2. Drug inhibits neurotransmitter synthesis.
  3. Drug prevents storage of neurotransmitter in vesicles.
  4. Drug stimulates the release of neurotransmitters.
  5. Drug inhibits neurotransmitter release.
  6. Drug stimulates postsynaptic receptors.
  7. Drug blocks postsynaptic receptors.
  8. Drug stimulates autoreceptors, inhibiting neurotransmitter release.
  9. Drug blocks autoreceptors, which increases the release of neurotransmitters.
  10. Drug inhibits the degradation of neurotransmitters.
  11. Drug blocks the reuptake mechanism.

NEUROTRANSMITTER TYPES

Amino Acids

  • Glutamate: Excitatory neurotransmitter.
  • GABA (Gamma-Aminobutyric Acid): Inhibitory neurotransmitter.

Monoamines

  • Serotonin: Modulates mood, emotion, and sleep patterns.
  • Catecholamines:
    • Dopamine: Involved in reward and motor functions.
    • Norepinephrine: Associated with arousal and alertness.
  • Acetylcholine: Involved in muscle activation and memory.

Neuropeptides

  • Endorphins: Involved in pain relief and pleasurable sensations.
  • Enkephalins: Similar roles to endorphins.

Lipids

  • Anandamide: An endogenous cannabinoid.

Gases

  • Nitric Oxide: Acts as a signaling molecule in the central nervous system.

POSTSYNAPTIC DECISION-MAKING

  • EPSP: A process that leads to the depolarization of the postsynaptic neuron, making it more likely to fire an action potential.
  • IPSP: A process that results in hyperpolarization, leading to decreased likelihood of an action potential firing.

Dendritic Field

  • Diagram: Illustrates relationship between excitatory and inhibitory synapses.

Summation Types

  1. Spatial Summation: Addition of EPSPs occurring at separate spatial locations on the membrane.
    • Example: EPSPs produced at the same time but on separate parts of the membrane do not influence each other, while close EPSPs can sum to form a larger EPSP.
  2. Temporal Summation: Addition of EPSPs occurring closely in time.
    • Example: Additional excitation overcoming inhibition leads to action potential firing.

POSTSYNAPTIC RECEPTORS

  • Ionotropic Receptors: Ligand-gated receptors that change membrane voltage upon binding with neurotransmitters.
  • Metabotropic Receptors: These are membrane proteins linked to G proteins that influence cellular processes through secondary messengers.

G Protein Structure

  • Composed of three subunits: Alpha, Beta, and Gamma.
    • Activation: Alpha subunit detaches and interacts with other proteins upon neurotransmitter binding.
    • Secondary Messenger Cascade: Initiates amplification of the signal across downstream proteins.

Examples of Secondary Messengers

  • Cyclic Adenosine Monophosphate (cAMP): Levels controlled by various neurotransmitters; notably high during opioid withdrawal, contributing to pharmacodynamic tolerance.

NEUROTRANSMITTER ACTIVATING SYSTEMS

  • Overview: Organization of neurochemical systems within the central nervous system (CNS). Neural pathways coordinate overall brain activity through a primary signaling neurotransmitter.
    • Cell Bodies: Located in brainstem nuclei, including the reticular activating system with extensive CNS distribution.

Cholinergic System (Acetylcholine)

  • Function: Critical for maintaining attention and EEG patterns; involved in memory by sustaining neuron excitability.
  • Relation to Alzheimer’s: Death of cholinergic neurons and decreased ACh in neocortex linked to Alzheimer’s disease.

Dopaminergic System (Dopamine)

  • Target Areas: Predominantly the cortex in the frontal lobe, particularly the ventral tegmental area (mesolimbic pathway) and the substantia nigra (nigrostriatal pathway).

Noradrenergic System (Norepinephrine)

  • Function: Maintains emotional tone; alterations in NE activity linked to depression and mania, also plays a role in attention-deficit/hyperactivity disorder (ADHD).

Serotonergic System (Serotonin)

  • Role: Maintains waking patterns, regulated serotonin linked to various psychological disorders (e.g., OCD, tics, schizophrenia) and physical disorders like sleep apnea and Sudden Infant Death Syndrome (SIDS).

HORMONES

  • Definition: Hormones are essentially neurotransmitters present in the blood, playing critical roles in the body.
  • Endocrine System: Slow communication in contrast to the nervous system; hormones influence body development, brain function, sexual function, and stress responses.

CONTROL OF HORMONES

  • Hypothalamus Actions: Produces neurohormones to stimulate the pituitary gland for hormone regulation.
  • Pituitary Gland Functions: Secretes releasing hormones that guide other endocrine glands, releasing appropriate hormones into the bloodstream.

HYPOTHALAMUS FUNCTIONS

Posterior Pituitary

  • Hormones Released:
    • Oxytocin: Associated with nurturing behavior, hugging, social bonding, and sexual activities.
    • Vasopressin: Prevents loss of water from the body, thereby reducing urine production.

Anterior Pituitary

  • Releasing Hormones: Such hormones can increase or decrease hormonal release, synthesized directly in the anterior pituitary itself.
  • Key Hormones and Functions:
    • Adrenocorticotrophic Hormone (ACTH): Controls adrenal cortex secretions, related to stress and fear responses.
    • Thyroid-Stimulating Hormone (TSH): Regulates secretion from the thyroid gland, involved in metabolism.
    • Follicle-Stimulating Hormone (FSH): Controls gonadal secretions, influencing development and reproduction.
    • Luteinizing Hormone (LH): Regulates gonadal secretions, affecting testosterone production and reproduction.
    • Prolactin: Manages secretion from mammary glands, facilitating milk production in females.
    • Growth Hormone (GH): Promotes bodily growth and development across systems.

GLUCOCORTICOIDS AND STRESS

  • Definition of Stressor: A stimulus that challenges the body’s homeostasis, triggering arousal and physiological responses.
  • Stress Response Mechanisms: Fast-acting responses primed for “fight-or-flight” using epinephrine, while slow-acting responses involve cortisol for resource mobilization and stress damage repair.