The Nervous System: A Comprehensive Overview

1. Types of Communication in the Nervous System

1. Electrical (nerve impulse / action potential) - rapid, direct transmission of signals along nerve fibers
2. Chemical (synaptic / neurotransmitter-based) - communication between neurons or between neurons and effector cells at the synapse, using chemical messengers (neurotransmitters)
3. Hormonal (neuroendocrine) - slower, blood-borne signaling where hormones released by neural or endocrine tissue act at distant targets

• Electrical signals within a single neuron (action potentials along the axon)
• Chemical signals between neurons (across the synaptic cleft)

2. Definition of the Nervous System

• Central Nervous System (CNS): brain + spinal cord
• Peripheral Nervous System (PNS): all nerve tissue outside the CNS (cranial nerves, spinal nerves, ganglia)

"Nervous tissue develops in the early embryo when the dorsal ectoderm neural plate folds lengthwise to form the neural tube, the precursor of the CNS, and releases neural crest cells, precursors for much of the PNS."

• Junqueira's Basic Histology

3. Brain and Spinal Cord

The Brain

The Spinal Cord

1. Relay station - transmits sensory signals up to the brain and motor commands down to the body
2. Reflex center - mediates spinal reflexes independently of the brain

• Gray matter (central, H-shaped) - contains neuron cell bodies; dorsal horns (sensory), ventral horns (motor)
• White matter (peripheral) - contains myelinated axon tracts carrying ascending (sensory) and descending (motor) signals

• Lateral corticospinal (pyramidal) tract - voluntary motor control
• Reticulospinal tract - posture and gait
• Spinothalamic tract - pain and temperature sensation

4. Somatic vs. Autonomic Nervous System

Somatic Nervous System (SNS)

• Controls voluntary, conscious movement of skeletal muscles
• Carries sensory information (touch, pain, temperature, proprioception) from the body to the CNS
• Uses single myelinated motor neurons that synapse directly on skeletal muscle at the neuromuscular junction
• Responses are generally rapid and under conscious control

Autonomic Nervous System (ANS)

• Controls involuntary functions: heart rate, blood pressure, digestion, gland secretion, bladder, sexual function
• Uses two-neuron chains (preganglionic + postganglionic neurons) rather than single neurons
• Further divided into:

5. How Nerve Impulses Are Initiated and Transmitted

Resting Membrane Potential

• At rest, the inside of a nerve fiber (axoplasm) is -70 mV relative to the outside
• This is maintained by:
  • High Na+ outside, high K+ inside the membrane
  • Voltage-gated Na+ channels closed; K+ channels partially open
  • Na+/K+-ATPase pump actively maintaining the gradient

Initiation of an Action Potential

1. A stimulus (mechanical, chemical, or electrical) raises the membrane potential toward zero
2. When it reaches the threshold (approximately -55 mV), voltage-gated Na+ channels open rapidly
3. Massive Na+ influx → membrane potential shoots from -70 mV to +20 to +30 mV (depolarization)
4. This is a positive-feedback cycle - more depolarization opens more Na+ channels
5. At +20 mV, Na+ channels inactivate and K+ channels open → K+ rushes out → repolarization back to -70 mV (and briefly hyperpolarizes = refractory period)

Propagation Along the Axon

• The depolarized region creates local current flow to adjacent membrane, raising its potential
• This triggers the next segment to depolarize - propagating the impulse in one direction (unidirectional because the segment just fired is in its refractory period)
• In myelinated fibers: current jumps between nodes of Ranvier (saltatory conduction) - much faster than in unmyelinated fibers
• In unmyelinated fibers: propagation is slow and continuous

"The functional nerve unit includes the nerve axon and its surrounding Schwann cell sheath... Junctions between sheaths along the axon, called nodes of Ranvier, contain sodium channels necessary for depolarization."

• Roberts and Hedges' Clinical Procedures in Emergency Medicine

6. What Is a Synapse?

Structure of a Synapse

• Presynaptic terminal (axon terminal of the sending neuron) - contains synaptic vesicles filled with neurotransmitter
• Synaptic cleft - a narrow gap (~20-40 nm) between the two cells
• Postsynaptic membrane - membrane of the receiving neuron/effector cell containing receptor proteins

How Synaptic Transmission Works

1. Action potential arrives at the presynaptic terminal
2. Voltage-gated Ca2+ channels open → Ca2+ enters the terminal
3. Ca2+ triggers exocytosis of synaptic vesicles → neurotransmitter released into the cleft
4. Neurotransmitter diffuses across the cleft and binds postsynaptic receptors
5. Receptor activation opens ion channels → new action potential initiated (excitatory synapse) OR inhibits the postsynaptic cell (inhibitory synapse)
6. Neurotransmitter is then inactivated by enzymes, reuptake, or diffusion

"Such nerve communication is transmitted to another neuron or effector cell via a synapse, where neurotransmitter is released at the presynaptic membrane and binds receptors on the postsynaptic cell, initiating a new action potential there."

• Junqueira's Basic Histology

Types of Synapses

• Axodendritic - axon to dendrite (most common)
• Axosomatic - axon to cell body
• Axoaxonic - axon to axon (modulating transmission)
• Neuromuscular junction - motor neuron to skeletal muscle

7. How the Nervous System Connects with the Body

Sensory (Afferent) Pathway

• Sensory receptors throughout the body (skin, muscles, organs, special senses) detect stimuli
• Signals travel via afferent nerves → spinal cord → brain
• Types: mechanoreceptors (touch/pressure), thermoreceptors (temperature), nociceptors (pain), chemoreceptors, photoreceptors

Motor (Efferent) Pathway

• Brain generates commands → travel via efferent nerves → muscles/glands
• Somatic efferents → skeletal muscle (voluntary movement)
• Autonomic efferents → smooth muscle, cardiac muscle, glands (involuntary)

Structural connections

• 31 pairs of spinal nerves emerge from the spinal cord (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal), each with a dorsal root (sensory) and ventral root (motor)
• 12 pairs of cranial nerves connect directly to the brainstem (smell, vision, eye movement, facial sensation, hearing, taste, swallowing, heart/gut control, neck/tongue movement)
• Plexuses (brachial, lumbar, sacral) - networks where spinal nerves merge and redistribute to innervate the limbs

8. Malfunctions of the Nervous System

Structural / Degenerative

Functional / Electrical

Peripheral

Psychiatric / Neurodevelopmental

9. Multiple Sclerosis (MS)

Definition

Epidemiology

• Primarily affects adults aged 20-50 years
• Twofold predilection for women (female:male ~ 2:1)
• Approximately 2.3 million people worldwide (Multiple Sclerosis International Federation, 2016)
• Most common age of onset: 30-38 years

Pathophysiology

• The disease is immune-mediated (though the exact trigger is unknown)
• Characterized by neural demyelination with relative axonal sparing (early disease)
• Loss of myelin impairs saltatory conduction and reduces conduction velocity → neurological deficits
• Demyelinating lesions (plaques) range from 1 mm to 4 cm and are scattered throughout CNS white matter
• Most commonly affects:
  • Lateral corticospinal (pyramidal) tracts of the cervical spinal cord
  • Reticulospinal columns
  • Optic nerves
  • Cerebral cortex and midbrain

Clinical Types

Common Symptoms

• Optic neuritis - blurred vision, pain with eye movement
• Pyramidal tract signs - weakness, spasticity, hyperreflexia
• Cerebellar signs - ataxia, tremor, dysarthria
• Bladder/bowel dysfunction - urgency, frequency, incontinence (50-90% of patients)
• Sexual dysfunction
• Fatigue (very common)
• Depression (37-54% of patients; suicide risk 2-7x the general population)
• Cognitive impairment - memory, processing speed, executive function

Diagnosis

• MRI is the cornerstone - shows T2 hyperintense demyelinating plaques (periventricular, juxtacortical, infratentorial, spinal)
• Cerebrospinal fluid - oligoclonal bands, elevated IgG index
• Visual evoked potentials - delayed latency in optic neuritis
• McDonald Criteria (2017) used for diagnosis

Treatment

• Acute relapses: high-dose IV methylprednisolone (corticosteroids)
• Disease-modifying therapies (DMTs): interferon beta, glatiramer acetate, natalizumab, ocrelizumab, siponimod, and others - reduce relapse rate and slow progression
• Symptomatic management: baclofen (spasticity), anticholinergics (bladder), antidepressants (depression), physiotherapy

"This demyelination causes impairment of saltatory conduction and conduction velocity in axonal pathways, resulting in various neurologic abnormalities that are subject to exacerbation and remission."

• Campbell Walsh Wein Urology