Neuroscience Chapter on Synapses and Neurotransmitters

Nervous System Lectures

•  The nervous system lectures are scheduled for Tuesday, November 19th on cells and synaptic transmission; Wednesday, November 20th on membrane and action potentials; Tuesday, November 26th on the autonomic nervous system; and Wednesday, November 27th on graded potentials, neuromuscular junctions, and a recap exercise.

Lecture Content - 1st Hour

•  The first hour of the lecture covers an introduction to neurons and basic neuroanatomy along with an introduction to non-neuronal cells in the nervous system.
•  Suggested reading is Silverthorn, Human Physiology: An Integrated Approach, 7th edition, Chapters 5, 8, and 11; and Rang et al., Rang and Dales Pharmacology, 8th edition, sections of chapters 4, 12, 13, and 14.

Organisation of the NS

•  The nervous system (NS) is organised into two main parts: - Central nervous system (CNS) — comprises of the brain and spinal cord - Peripheral nervous system (PNS) — comprises nerves outside of the CNS that extend to and from the brain and spinal cord.

Functions of the Nervous System

•  Sensory Function: afferent neurons transmit sensory information from the periphery to the CNS.
•  Processing function: the CNS processes the incoming sensory information and initiates a response that modifies a process.
•  Motor function: efferent neurons transmit motor signals that travel from the CNS to the periphery.

Sensory & Motor Information Types

•  PNS has two divisions    - Sensory (afferent) division includes:        - Somatic sensory (general): touch, pain, pressure, vibration, temperature, proprioception (body position) in skin, body walls, and limbs. (Special senses include: hearing, equilibrium, vision, smell)        - Visceral sensory (general): stretch, pain, temperature, chemical changes, and irritation of viscera (internal organs), such as nausea, hunger        - Special senses include: taste    - Motor (efferent) division includes:        - Somatic motor (voluntary motor): motor innervation to all skeletal muscles        - Visceral motor (involuntary): motor innervation to smooth muscle, cardiac muscle, and glands. This is equivalent to the autonomic nervous system (ANS).

The Neuron

•  Functional unit of the nervous system
•  Estimated to contain 86 billion neurons in the human brain.
•  Neurons can live and function for a lifetime.
•  Foetal neurons lose their ability to undergo mitosis — neural stem cells are the exception.
•  Require abundant glucose and oxygen.

The Neuron - Structure

•  Cell body (biosynthetic center and receptive region): contains nucleus, organelles plus other structures, chromatophilic bodies (Nissl bodies), clusters of rough ER and ribosomes; located within the CNS
•  Dendrites: extensive branching from the cell body, transmit electrical signals towards the cell body.
•  Axon: nerve fiber, impulse generator and conductor; transmits action potentials away from the cell body
•  Axon Terminal: secretory component

The Neuron - Structure

•  Myelin sheath: protective covering around some axons, enables saltatory conduction. Increases the speed of transmission.
•  Synapse: region where axons transmit to target cells, via neurotransmitters.
•  Ganglia: clusters of cell bodies in the PNS.

Neuron Classes

•  Unipolar: Single axon, sensory neurons
•  Bipolar: Single dendrite, single axon, found as sensory neurons in ear, eye, and nose.
•  Pseudounipolar: Single axon branches to connect to spinal cord or CNS neurons; found as sensory neurons
•  Multipolar: Single axon, multiple dendrites, most common type of neuron; found as interneurons (within CNS) and motor neurons

Glial Cells

•  Support cells of the nervous system.
•  6 types: - CNS Neuroglial cells: astrocytes (chemical environment), microglia (phagocytic), ependymal (CSF), oligodendrocytes (myelin)
•  PNS Non-neuroglial cells: Schwann cells (myelin), satellite cells (chemical environment)

Schwann Cells

•  Produce the myelin sheath in the PNS.
•  Protect axons and insulate them. 
•  Myelinated axons conduct action potentials more quickly.
•  Maintains microenvironment, assists neural repair, enables saltatory conduction.

Summary - 1st Hour

•  Neurons have common structural features but can be classified on anatomical features.
•  The nervous system contains additional non-neuronal cells with diverse functions.

Lecture Content - 2nd Hour

•  Introduction to electrical synapses
•  Introduction to chemical synaptic transmission
•  Suggested reading: Silverthorn, Human Physiology: An Integrated Approach, 7th edition, chapters 5, 8, and 11; and Rang et al., Rang and Dales Pharmacology, 8th edition, sections of chapters 4, 12, 13, and 14.

The Synapse

•  Synapse: the connection between a neuron and another cell
•  Chemical Synapse:    - synaptic cleft [20-50 nm]—space between two communicating cells    - presynaptic density – axon terminal    - synaptic vesicles containing neurotransmitter molecules    - postsynaptic density – dendrite or cell body

The Synapse - Electrical

•  Direct transfer of ionic current from one cell to the next.
•  Gap junction formed by connexons — channels formed by six connexions.
•  Cell membranes connected by connexons.
•  allow ions to pass from one cell to another.
•  found in smooth muscle and the heart.

The Synapse - Chemical

•  presynaptic neuron releases neurotransmitter into synaptic cleft.
•  neurotransmitter binds to receptors on postsynaptic cell
•  causes a response in the postsynaptic cell

Neurotransmitters

•  Substances released by a neuron, affecting transmission of information to a post-synaptic target.
•  Criteria: method of synthesis, storage, mechanism of release, mechanism of removal

Neurotransmitters - More

•  Nerve stimulation must result in release of sufficient transmitter to elicit observed response.
•  Response must be mimicked when applied exogenously.
•  Antagonists must block both endogenous and exogenous transmitters.

Neurotransmitter Classes

•  Major Neurotransmitters in the CNS:
•  glutamate (principle excitatory), GABA (principle inhibitory)
•  Acetylcholine — parasympathetic function, memory
•  Noradrenaline — sympathetic function

Neurotransmitter Release

•  Exocytosis: Process by which vesicles release their contents.

The Chemical Synapse - steps

•  Neurotransmitter synthesis
•  Neurotransmitter loaded into synaptic vesicles
•  Action potential causes membrane depolarization
•  Voltage-gated Ca2+ channels open
•  Ca2+ triggers fusion of synaptic vesicles to presynaptic terminal
•  Neurotransmitter is released into the synaptic cleft by exocytosis
•  Neurotransmitter crosses the cleft and binds to postsynaptic receptors
•  Biochemical or electrical response elicited in postsynaptic cell.
•  Neurotransmitter removed.

The Chemical Synapse - Postsynaptic Receptors

•  Ionotropic    - Ligand-gated ion channels    - Ligand binding causes a conformational change that leads to the opening of channels.
•  Metabotropic    - G protein-coupled receptors    - Trigger slower, often longer-lasting actions.

Summary - 2nd Hour

•  Description of electrical and chemical synapses.
•  Neurotransmitter synthesis, storage, release, signal generation, and removal.