BS2015 Block 2 lecture 4

Lecture Topics:
- Introduction to Bioelectricity and Recap of Membrane and Equilibrium Potentials
- Passive Conduction in Neurons, including Time and Length Constants
- Ionic and Molecular Basis of the Action Potential, Experimental Investigations into Action Potentials and Local Current Circuit Theory
- Myelination: Myelination and Saltatory Conduction, Demyelinating Diseases

Structure & Function:
- Describe the structure and function of myelin and the Nodes of Ranvier.
Biological Process:
- Explain the biological process of myelination in both the Central Nervous System (CNS) and Peripheral Nervous System (PNS).
Saltatory Conduction:
- Explain the mechanism of saltatory conduction and its advantages over continuous conduction.
Demyelinating Diseases:
- Discuss how demyelinating diseases impair conduction and neural function.
Clinical Symptoms:
- Relate clinical symptoms to underlying changes in conduction physiology.

Quick Poll: Engaging with the question of why myelin matters in the context of neural conduction. Join code for TopHat course: 982675.
Regulation of Conduction Time:
- Temporal accuracy is vital for proper information transfer in the nervous system.
- The necessity for precise regulation of nerve conduction velocity arises.
- Myelination of axons was described as early as 1854 and is crucial for increasing the speed of conduction.
- Optimal Conduction Velocity: Evolution has favored maximization of conduction velocity in some axons, while others require precision timing in conduction.

Cell Types:
- Neurons are the main cells of the nervous system, accompanied by various supporting cells:
- Microglia: Neuroimmune cells that perform various roles in maintenance and defense.
- Astrocytes: Cells that provide structural support, nutrient transport, and modulation of synaptic transmission.
- Oligodendrocytes (CNS) and Schwann Cells (PNS): Responsible for myelination.

When Does Myelination Occur?:
- Begins prenatally, approximately mid-gestation (around 14-16 weeks in humans), primarily in spinal cord and brainstem.
- Accelerates postnatally, especially during the first 2-3 years of life.
- Continues into adolescence and early adulthood, tapering off towards middle age.

Key Cell Types:
- CNS: Oligodendrocytes, which myelinate multiple axons.
- PNS: Schwann Cells, which myelinate a single segment of an axon.
- Both types derive from precursor cells:
- Oligodendrocytes from oligodendrocyte precursor cells (OPCs).
- Schwann Cells from neural crest cells.
Myelination refers to the formation of a protective myelin sheath around axons which enhances conduction.
Non-myelinated Neurons: In these cases, single glial cells surround numerous axons, not achieving the insulating effects of myelination.

Myelin Sheath Structure:
- Composed of repetitive multi-layered proteolipid membranes.
- Presence of Nodes of Ranvier: segments where the axonal membrane is exposed, critical for conduction.

Functionality:
- Caspr channels (voltage-gated sodium channels), and KV channels (voltage-gated potassium channels).
- Insulation Properties:
- Increases membrane resistance, thereby reducing capacitance.
- Speeds up passive conduction.

Definition: Refers to the ‘jumping’ of action potentials between Nodes of Ranvier, initiated by local circuit currents that depolarize adjacent nodes above threshold.
Mechanism:
- Involves electrotonic conduction where action potentials are actively propagated.

Nodes of Ranvier:
- Characterized by short time constants and high densities of sodium channels.
Internodes:
- Have very high membrane resistance and long length constants with lower levels of ion channels.
Regulation of Conduction:
- Qualitative variations in myelination (internode distance, myelin sheath thickness, axon diameter) impact conduction velocity.

Neurological Disorders: Example - Multiple Sclerosis (MS)
- A chronic autoimmune disease characterized by inflammatory demyelination.
- Symptoms:
- Vision impairment, numbness, tingling, focal weakness, bowel and bladder dysfunction, cognitive impairment.
- The disease was first defined by Jean-Martin Charcot in 1868.
Diagnosis of MS:
- Involves review of medical history, symptom testing, physical/neurological exams, and MRI scans.
- MRI reveals lesions that appear as bright white spots. Collection of cerebrospinal fluid (CSF) via lumbar puncture aids in assessing immune activity in the nervous system.

Process:
- Autoimmune attacks lead to the activation of astrocytes and recruitment and activation of microglia.

Steps involved in the process:
1. Activation and migration of microglia.
2. Recruitment and proliferation of oligodendrocyte precursor cells (OPCs).
3. Synthesis and assembly of myelin proteins.

Altered Conduction Properties:
- Decreased conduction velocity due to higher capacitance and lower resistance in demyelinated internodes.
- Changes lead to slower action potential rise and altered peak amplitude.
Recording Action Potentials:
- Action potentials recorded from demyelinated lesions were notably smaller, with a reduced conduction velocity and prolonged refractory period.

Saltatory Conduction: Action potentials propagate through jumping in myelinated neurons.
Myelination: Crucial for enhancing conduction velocity through axonal insulation.
Demyelination Effects: Conditions like MS alter conduction properties, leading to significant neural function impairment and symptoms.
Conclusion: Understanding the mechanisms and implications of myelination and demyelination is vital for insights into neural conduction dynamics and neurological disorders.