Chapter 5.5: Neural Control and Coordination

1. Neuron and Nerves

Neuron (Nerve Cell): A neuron is a microscopic structure composed of three major parts, namely, the cell body, dendrites and axon. It is the structural and functional unit of the nervous system.
- Cell Body (Soma or Cyton): Contains the cytoplasm with typical cell organelles and certain granular bodies called Nissl’s granules.
- Dendrites: Short fibres which branch repeatedly and project out of the cell body. They also contain Nissl’s granules. Dendrites transmit electrical impulses towards the cell body.
- Axon: A long fibre, the distal end of which is branched. Each branch terminates as a bulb-like structure called a synaptic knob which possesses synaptic vesicles containing chemicals called neurotransmitters. The axon transmits nerve impulses away from the cell body to a synapse or to a neuromuscular junction.
Nerves: In the peripheral nervous system, the axons of neurons are bundled together to form a nerve. Nerves are covered by connective tissue sheaths.

Types of Neurons

Based on the number of axon and dendrites, the neurons are divided into four types:

Unipolar Neuron: Cell body with one axon only. Found usually in the embryonic stage.
Bipolar Neuron: With one axon and one dendrite. Found in the retina of the eye and the olfactory epithelium.
Multipolar Neuron: With one axon and two or more dendrites. Found in the cerebral cortex.
Pseudounipolar Neuron: A single process arises from the cell body and then divides into an axon and a dendrite. Found in the dorsal root ganglia of the spinal cord.

Types of Axons

Myelinated Nerve Fibre: The axon is enveloped with Schwann cells, which form a myelin sheath around the axon. The gaps between two adjacent myelin sheaths are called nodes of Ranvier. Found in spinal and cranial nerves.
Non-myelinated Nerve Fibre: The axon is enclosed by a Schwann cell that does not form a myelin sheath around the axon. Found in autonomous and the somatic neural systems.

2. Generation and Conduction of Nerve Impulse

A nerve impulse is a wave of electrochemical change that travels along a neuron.

a) Resting Potential (Polarized State)

In a resting neuron (a neuron not conducting any impulse), the axonal membrane is more permeable to potassium ions (K+) and nearly impermeable to sodium ions (Na+). Similarly, the membrane is impermeable to negatively charged proteins present in the axoplasm.
Consequently, the axoplasm inside the axon contains a high concentration of K+ and negatively charged proteins and a low concentration of Na+.
In contrast, the fluid outside the axon contains a low concentration of K+ and a high concentration of Na+ and thus forms a concentration gradient.
This ionic gradient across the resting membrane is maintained by the active transport of ions by the sodium-potassium pump (Na+-K+ Pump) which transports 3 Na+ outwards for 2 K+ into the cell.
As a result, the outer surface of the axonal membrane possesses a positive charge while its inner surface becomes negatively charged. The electrical potential difference across the resting plasma membrane is called as the resting potential. The membrane is said to be polarized.

b) Action Potential (Depolarized State)

When a stimulus is applied, the membrane at the site becomes freely permeable to Na+.
This leads to a rapid influx of Na+ followed by the reversal of the polarity at that site, i.e., the outer surface of the membrane becomes negatively charged and the inner side becomes positively charged. This reversal of polarity is called depolarization.
The electrical potential difference across the plasma membrane at the site of the action potential is called the action potential, which is in fact termed as a nerve impulse.

c) Repolarization

At the peak of the action potential, the permeability to Na+ decreases, and the membrane becomes more permeable to K+.
K+ ions diffuse outwards, and the membrane potential returns towards the resting potential. This is called repolarization.

d) Conduction of Nerve Impulse

At sites immediately ahead, the axon membrane has a positive charge on the outer surface and a negative charge on its inner surface. As a result, a current flows on the inner surface from the site of the action potential to the next site. On the outer surface, a current flows from the next site to the site of the action potential to complete the circuit.
Hence, the polarity at the site is reversed, and an action potential is generated at the next site. Thus, the impulse (action potential) generated at one point arrives at the next point. This sequence is repeated along the length of the axon and consequently, the impulse is conducted.
Saltatory Conduction: In myelinated nerve fibres, the action potential jumps from one node of Ranvier to the next. This type of conduction is much faster than in non-myelinated fibres.

3. Synaptic Transmission

A nerve impulse is transmitted from one neuron to another through junctions called synapses.

Synapse: A synapse is formed by the membranes of a pre-synaptic neuron and a post-synaptic neuron, which may or may not be separated by a gap called the synaptic cleft.
Types of Synapses:
- Electrical Synapse: The membranes of pre- and post-synaptic neurons are in very close proximity. Electrical current can flow directly from one neuron into the other across these synapses. Transmission of an impulse across electrical synapses is very similar to impulse conduction along a single axon. Impulse transmission across an electrical synapse is always faster than that across a chemical synapse.
- Chemical Synapse: The membranes of the pre- and post-synaptic neurons are separated by a fluid-filled space called the synaptic cleft. Chemicals called neurotransmitters are involved in the transmission of impulses at these synapses.

Mechanism of Chemical Synaptic Transmission

When an action potential arrives at the axon terminal (synaptic knob), it stimulates the movement of the synaptic vesicles towards the membrane where they fuse with the plasma membrane and release their neurotransmitters into the synaptic cleft.
The released neurotransmitters bind to their specific receptors, present on the post-synaptic membrane.
This binding opens ion channels allowing the entry of ions which can generate a new potential in the post-synaptic neuron. The new potential developed may be either excitatory or inhibitory.

Neurotransmitters: These are chemicals that transmit signals across a chemical synapse. Examples include Acetylcholine, Dopamine, Serotonin, GABA (Gamma-Aminobutyric Acid), etc.

4. Human Nervous System

a) Central Nervous System (CNS)

The CNS includes the brain and the spinal cord and is the site of information processing and control.

i) Brain

Forebrain (Prosencephalon):
- Cerebrum: Forms the major part of the human brain. A deep cleft divides the cerebrum longitudinally into two halves, which are termed as the left and right cerebral hemispheres. The hemispheres are connected by a tract of nerve fibres called corpus callosum. The layer of cells which covers the cerebral hemisphere is called the cerebral cortex and is thrown into prominent folds. The cerebral cortex is referred to as the grey matter due to its greyish appearance. The cerebral cortex contains motor areas, sensory areas and large regions that are neither clearly sensory nor motor in function. These regions called as the association areas are responsible for complex functions like intersensory associations, memory and communication. The inner part of the cerebral hemisphere consists of fibres of the tracts covered with the myelin sheath, which constitute the white matter.
- Thalamus: A major coordinating centre for sensory and motor signaling.
- Hypothalamus: Lies at the base of the thalamus. It contains a number of centres which control body temperature, urge for eating and drinking. It also contains several groups of neurosecretory cells, which secrete hormones called hypothalamic hormones.
Midbrain (Mesencephalon): Located between the thalamus/hypothalamus of the forebrain and pons of the hindbrain. A canal called the cerebral aqueduct passes through the midbrain. The dorsal portion of the midbrain consists mainly of four round swellings (lobes) called corpora quadrigemina.
Hindbrain (Rhombencephalon):
- Pons: Consists of fibre tracts that interconnect different regions of the brain.
- Cerebellum: Has a very convoluted surface in order to provide the additional space for many more neurons. It is responsible for the regulation of balance and coordination of voluntary movements.
- Medulla Oblongata: Connected to the spinal cord. The medulla contains centres which control respiration, cardiovascular reflexes and gastric secretions.

ii) Spinal Cord

Structure: A long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column. The spinal cord is covered by the same three meninges as the brain. The grey matter is in the centre (H-shaped) and the white matter is on the outside.
Functions:
1. Conducts sensory and motor impulses to and from the brain.
2. Acts as a centre for reflex actions.

b) Peripheral Nervous System (PNS)

The PNS comprises all the nerves of the body associated with the CNS (brain and spinal cord).

Somatic Nervous System: Relays impulses from the CNS to skeletal muscles.
Autonomic Nervous System (ANS): Transmits impulses from the CNS to the involuntary organs and smooth muscles of the body. The ANS is further classified into the sympathetic and parasympathetic nervous systems.

c) Visceral Nervous System

The part of the peripheral nervous system that comprises the whole complex of nerves, fibres, ganglia, and plexuses by which impulses travel from the central nervous system to the viscera and from the viscera to the central nervous system. It is a part of the autonomic nervous system.

Sense Organs and Sensory Systems

Introduction to Sensory Systems

Sensory organs are specialized structures that detect environmental stimuli and convert them into neural signals through a process called transduction. The five primary senses work together with the nervous system to provide comprehensive information about our environment.

General Principles of Sensation

Adequate Stimulus: Each sense organ responds optimally to a specific type of energy
Threshold: Minimum stimulus intensity required for detection
Adaptation: Decreased response to constant stimulation
Sensory Coding: How stimulus properties are encoded in neural activity

The Eye and Vision

Anatomical Structure

External Structures

Eyelids (Palpebrae): Protect the eye, contain meibomian glands
Conjunctiva: Transparent membrane covering the sclera and inner eyelids
Lacrimal Apparatus: Produces and drains tears
- Lacrimal gland (tear production)
- Lacrimal puncta, canaliculi, sac, and nasolacrimal duct (drainage)

The Eyeball (Globe)

Three Layers:

Fibrous Layer (Outer)
- Sclera: White, tough connective tissue providing structure
- Cornea: Transparent, avascular, highly innervated anterior portion
  - Epithelium, Bowman's layer, stroma, Descemet's membrane, endothelium
Vascular Layer (Middle/Uvea)
- Choroid: Highly vascularized, provides nutrients to outer retina
- Ciliary Body: Contains ciliary muscle for accommodation
  - Ciliary processes secrete aqueous humor
- Iris: Colored portion with central opening (pupil)
  - Sphincter pupillae (constricts pupil, parasympathetic)
  - Dilator pupillae (dilates pupil, sympathetic)
Neural Layer (Inner)
- Retina: Light-sensitive tissue containing photoreceptors

Internal Structures

Aqueous Humor: Clear fluid in anterior and posterior chambers
Lens: Transparent, biconvex structure for focusing
Vitreous Humor: Gel-like substance filling posterior chamber
Optic Disc: Blind spot where optic nerve exits
Macula Lutea: Area of highest visual acuity
Fovea Centralis: Central depression in macula with only cones

Microscopic Structure of the Retina

Ten Layers (from inside to outside):

Inner Limiting Membrane
Nerve Fiber Layer: Axons of ganglion cells
Ganglion Cell Layer: Cell bodies of ganglion cells
Inner Plexiform Layer: Synapses between bipolar, amacrine, and ganglion cells
Inner Nuclear Layer: Bipolar cells, horizontal cells, amacrine cells, Müller cells
Outer Plexiform Layer: Synapses between photoreceptors and bipolar/horizontal cells
Outer Nuclear Layer: Cell bodies of photoreceptors
External Limiting Membrane
Photoreceptor Layer: Rods and cones
Retinal Pigment Epithelium (RPE)

Photoreceptors

Rods (120 million per eye)

Structure: Outer segment with rhodopsin-containing discs
Function: Detect light/dark, responsible for scotopic (night) vision
Distribution: Absent in fovea, highest density in peripheral retina
Sensitivity: Extremely sensitive to light, saturate in bright light

Cones (6 million per eye)

Types: S-cones (short wavelength/blue), M-cones (medium/green), L-cones (long/red)
Structure: Outer segment with photopsin-containing membrane folds
Function: Color vision and high acuity photopic (day) vision
Distribution: Concentrated in fovea and macula

Other Retinal Cells

Bipolar Cells: Transmit signals from photoreceptors to ganglion cells
Horizontal Cells: Lateral processing and contrast enhancement
Amacrine Cells: Complex processing and motion detection
Ganglion Cells: Generate action potentials, form optic nerve
Müller Cells: Glial support cells spanning entire retinal thickness

Phototransduction

Process in Rods:

Light absorption by rhodopsin (opsin + 11-cis retinal)
Conformational change to all-trans retinal
Activation of transducin (G-protein)
Activation of phosphodiesterase
Decreased cGMP levels
Closure of Na+ channels
Hyperpolarization of photoreceptor
Reduced neurotransmitter (glutamate) release

Visual Cascades:

ON-pathway: Depolarizing bipolar cells (sign-conserving)
OFF-pathway: Hyperpolarizing bipolar cells (sign-inverting)

Path of Light Through the Eye

Step-by-Step Light Journey

1. External Environment → Cornea

Light rays enter the eye through the transparent cornea
Cornea provides ~43 diopters of refractive power (65% of total)
Refraction occurs at air-cornea interface due to refractive index difference
Light rays begin converging toward the retina

2. Cornea → Anterior Chamber → Pupil

Light passes through aqueous humor in anterior chamber
Iris controls pupil size:
- Bright light: Sphincter pupillae contracts → miosis (small pupil)
- Dim light: Dilator pupillae contracts → mydriasis (large pupil)
Pupil diameter ranges from 1.5mm (bright) to 8mm (dark)

3. Pupil → Lens

Light enters the biconvex crystalline lens
Lens provides ~15-20 diopters (variable for accommodation)
Accommodation mechanism:
- Near objects: Ciliary muscle contracts → lens becomes more spherical (higher power)
- Far objects: Ciliary muscle relaxes → lens flattens (lower power)
Presbyopia: Age-related lens hardening reduces accommodation

4. Lens → Vitreous Chamber

Light travels through vitreous humor (gel-like substance)
Maintains eye shape and provides structural support
Transparent medium allows unimpeded light passage
Any floaters or opacities can cast shadows on retina

5. Vitreous → Retina

Light must pass through multiple retinal layers before reaching photoreceptors
Paradoxical arrangement: Light travels through neural layers first
Minimal light scattering due to transparent cellular organization
Foveal pit: Thinnest retinal area for optimal light access to cones

6. Retinal Processing

Photoreceptors (rods and cones) capture photons in outer segments
Light passes through retinal layers in reverse order:
1. Inner limiting membrane
2. Nerve fiber layer
3. Ganglion cell layer
4. Inner plexiform layer
5. Inner nuclear layer
6. Outer plexiform layer
7. Outer nuclear layer
8. External limiting membrane
9. Photoreceptor layer (final destination)
10. Retinal pigment epithelium (absorbs excess light)

Light Focusing Mechanics

Emmetropia (Normal Vision)

Parallel light rays from distant objects focus exactly on retina
Total refractive power: ~60 diopters
Axial length: ~24mm correlates with refractive power

Refractive Errors

Myopia: Light focuses anterior to retina (eyeball too long)
Hyperopia: Light focuses posterior to retina (eyeball too short)
Astigmatism: Irregular curvature causes multiple focal points

Visual Processing After Light Detection

Phototransduction Cascade (Detailed)

Dark State (Depolarized)

High cGMP levels keep cation channels open
Continuous Na+/Ca2+ influx maintains depolarization (~-30mV)
Glutamate release onto bipolar cells

Light State (Hyperpolarized)

Photon absorption by rhodopsin/photopsins
11-cis retinal → all-trans retinal conformational change
Transducin activation (G-protein cascade)
Phosphodiesterase activation breaks down cGMP
cGMP levels drop → cation channels close
Hyperpolarization to ~-70mV
Reduced glutamate release

Common Eye Abnormalities

Refractive Errors

Myopia (Nearsightedness): Eyeball too long, distant objects blurry
Hyperopia (Farsightedness): Eyeball too short, near objects blurry
Astigmatism: Irregular corneal curvature causing distorted vision
Presbyopia: Age-related loss of accommodation

Retinal Disorders

Macular Degeneration: Deterioration of central retina
Diabetic Retinopathy: Vascular damage from diabetes
Retinal Detachment: Separation of neurosensory retina from RPE
Retinitis Pigmentosa: Progressive degeneration of photoreceptors

Other Conditions

Glaucoma: Increased intraocular pressure damaging optic nerve
Cataracts: Lens opacity affecting vision clarity
Color Blindness: Deficiency in cone photopigments

The Ear and Hearing/Balance

Anatomical Structure

External Ear

Auricle (Pinna): Cartilaginous structure collecting sound waves
External Auditory Canal: S-shaped tube lined with ceruminous glands
Tympanic Membrane: Thin membrane separating external and middle ear

Middle Ear (Tympanic Cavity)

Ossicles (Tiny Bones):

Malleus (Hammer): Attached to tympanic membrane
Incus (Anvil): Intermediate bone
Stapes (Stirrup): Attached to oval window

Other Structures:

Eustachian Tube: Connects middle ear to nasopharynx
Stapedius and Tensor Tympani Muscles: Protect inner ear from loud sounds
Mastoid Air Cells: Air-filled spaces in temporal bone

Inner Ear (Labyrinth)

Bony Labyrinth:

Cochlea: Spiral structure for hearing
Vestibule: Central chamber containing saccule and utricle
Semicircular Canals: Three perpendicular canals for rotational movement detection

Membranous Labyrinth:

Cochlear Duct (Scala Media): Contains organ of Corti
Saccule and Utricle: Detect linear acceleration and head position
Semicircular Ducts: Detect rotational movements

Path of Sound Through the Ear

Step-by-Step Sound Journey

1. Sound Wave Generation → External Ear

Sound waves (pressure variations in air) enter the auricle (pinna)
Pinna shape helps collect and funnel sound waves
Sound localization: Pinna provides directional cues through filtering
Sound travels through external auditory canal (~2.5 cm length)

2. External Canal → Tympanic Membrane

External auditory canal acts as resonant tube
Natural resonance around 3000 Hz amplifies important speech frequencies
Cerumen (earwax) protects and lubricates canal
Sound waves strike tympanic membrane (eardrum)
Tympanic membrane vibration frequency matches sound wave frequency

3. Tympanic Membrane → Ossicular Chain (Middle Ear) Mechanical Advantage System:

Malleus (Hammer)

Manubrium attached to tympanic membrane
Vibrations transfer to head of malleus
Lever arm provides mechanical advantage

Incus (Anvil)

Body articulates with malleus head
Long process connects to stapes
Acts as intermediate link in ossicular chain

Stapes (Stirrup)

Footplate sits in oval window
Smallest bone in human body
Piston-like movement transfers energy to inner ear

Amplification Mechanisms:

Lever advantage: Malleus-incus lever ratio ~1.3:1
Area advantage: Tympanic membrane area (~55 mm²) vs oval window (~3.2 mm²)
Total amplification: ~20-fold increase in pressure
Impedance matching: Converts low-pressure air waves to high-pressure fluid waves

4. Oval Window → Inner Ear Fluids

Perilymph Movement (Scala Vestibuli and Tympani)

Stapes footplate movement creates pressure waves in perilymph
Perilymph composition: Similar to extracellular fluid (high Na+, low K+)
Wave propagation: From base to apex of cochlea
Frequency-dependent travel: High frequencies travel short distances, low frequencies travel further

Endolymph (Scala Media)

Unique composition: High K+ (~150 mM), low Na+ (~1 mM)
Endocochlear potential: +80mV relative to perilymph
Maintained by: Stria vascularis (ion pumps and channels)
Critical for: Hair cell depolarization

5. Cochlear Mechanics

Basilar Membrane Properties

Base (near oval window):
- Narrow (~0.1 mm) and stiff
- High-frequency response (20,000 Hz)
- Hair cells have short stereocilia
Apex (helicotrema):
- Wide (~0.5 mm) and flexible
- Low-frequency response (20 Hz)
- Hair cells have long stereocilia

Traveling Wave Theory (Georg von Békésy)

Progressive wave travels from base to apex
Peak amplitude occurs at frequency-specific location
Sharp tuning enhanced by outer hair cell active mechanisms
Envelope peak determines pitch perception

6. Hair Cell Activation

Mechanical Transduction Process:

Basilar membrane displacement causes relative motion
Tectorial membrane shears against hair cell stereocilia
Stereocilia deflection opens mechanotransduction channels
K+ influx from endolymph causes depolarization
Ca2+ influx triggers neurotransmitter release
Spiral ganglion activation generates action potentials

Hair Cell Types:

Inner Hair Cells (IHC) - Primary Sensors

Number: ~3,500 per cochlea
Function: Main sensory transduction
Innervation: 95% of auditory nerve fibers
Arrangement: Single row along cochlea
Neurotransmitter: Glutamate

Outer Hair Cells (OHC) - Amplifiers

Number: ~12,000 per cochlea (3 rows)
Function: Active amplification and tuning
Mechanism: Prestin-mediated electromotility
Effect: 40-60 dB amplification
Damage: Causes hearing loss and reduced frequency selectivity

7. Neural Encoding

Frequency Coding:

Place theory: Different frequencies activate different cochlear locations
Temporal theory: Phase-locking to stimulus waveform (up to ~1000 Hz)
Combination: Both mechanisms work together

Intensity Coding:

Rate coding: Higher intensity → higher firing rates
Population coding: More neurons recruited
Dynamic range: ~120 dB range compressed into neural firing rates

8. Central Auditory Processing

Auditory Pathway Sequence:

Spiral ganglion → Cochlear nerve (CN VIII)
Cochlear nuclei (ventral and dorsal)
Superior olivary complex (sound localization)
Inferior colliculus (midbrain integration)
Medial geniculate nucleus (thalamic relay)
Primary auditory cortex (temporal lobe)

Sound Localization Mechanisms:

Interaural time differences (ITD): Sound arrival time differences
Interaural level differences (ILD): Sound intensity differences
Head-related transfer function: Pinna and head filtering effects

Protective Mechanisms

Acoustic Reflex

Stapedius muscle: Contracts to loud sounds (>70-90 dB)
Tensor tympani: Additional protection
Function: Reduces transmission by ~20 dB
Latency: 40-160 milliseconds (too slow for sudden loud sounds)

Eustachian Tube

Pressure equalization: Connects middle ear to nasopharynx
Opens during: Swallowing, yawning, sneezing
Dysfunction: Can cause conductive hearing loss

Organ of Corti (Hearing Receptor)

Location: Spiral organ within cochlear duct

Key Structures:

Basilar Membrane: Supporting structure with tonotopic organization
Hair Cells: Mechanoreceptors with stereocilia
- Inner Hair Cells (IHC): ~3,500 cells, primary sensory receptors
- Outer Hair Cells (OHC): ~12,000 cells, amplify and fine-tune response
Tectorial Membrane: Overlying structure that contacts hair cell stereocilia
Supporting Cells: Pillar cells, Deiters' cells, Hensen's cells

Mechanotransduction in Hair Cells

Sound waves cause basilar membrane displacement
Stereocilia deflection opens mechanically-gated K+ channels
K+ influx (from K+-rich endolymph) causes depolarization
Ca2+ influx triggers neurotransmitter release
Spiral ganglion neurons generate action potentials

Frequency Coding

Place Theory: Different frequencies activate different regions of basilar membrane
Base: High frequencies (20,000 Hz)
Apex: Low frequencies (20 Hz)
Temporal Coding: Phase-locking for frequencies below 1,000 Hz

Balance (Vestibular System)

Otolith Organs

Saccule and Utricle:

Macula: Sensory epithelium with hair cells
Otolithic Membrane: Contains calcium carbonate crystals (otoconia)
Function: Detect linear acceleration and head position relative to gravity

Semicircular Canals

Three Canals: Anterior, posterior, lateral (horizontal)

Ampulla: Enlarged region containing crista ampullaris
Cupula: Gelatinous structure deflected by endolymph movement
Function: Detect rotational movements

Hair Cell Types

Type I: Flask-shaped, surrounded by calyx ending
Type II: Cylindrical, contacted by bouton endings
Kinocilium: Single true cilium (absent in cochlear hair cells)
Stereocilia: Actin-filled projections arranged by height

Common Hearing and Balance Disorders

Hearing Loss

Conductive: Problem in external/middle ear (cerumen, otitis media, otosclerosis)
Sensorineural: Inner ear or neural damage (presbycusis, noise-induced, ototoxicity)
Mixed: Combined conductive and sensorineural components

Vestibular Disorders

Benign Paroxysmal Positional Vertigo (BPPV): Displaced otoconia
Ménière's Disease: Excess endolymph causing vertigo, hearing loss, tinnitus
Vestibular Neuritis: Inflammation of vestibular nerve
Labyrinthitis: Inflammation affecting both hearing and balance

The Nose and Olfaction

Anatomical Structure

External Nose

Nasal Bones: Form bridge of nose
Cartilages: Lateral, septal, and alar cartilages provide shape
Nostrils (Nares): External openings

Nasal Cavity

Nasal Septum: Divides cavity into left and right sides
Conchae (Turbinates): Three bony projections creating air turbulence
- Superior, middle, and inferior conchae
Meati: Spaces beneath each concha

Olfactory Region

Location: Superior portion of nasal cavity and upper septum
Area: ~5 cm² each side in humans
Olfactory Mucosa: Specialized pseudostratified epithelium

Olfactory Epithelium

Cell Types

Olfactory Receptor Neurons (ORNs)
- Bipolar neurons with apical dendrites and basal axons
- Olfactory Cilia: 10-30 non-motile cilia containing odorant receptors
- Lifespan: 30-60 days, continuously replaced
Supporting (Sustentacular) Cells
- Columnar cells providing structural support
- Secretions: Mucus and detoxifying enzymes
- Insulation: Electrical isolation between ORNs
Basal Cells
- Stem cells for ORN replacement
- Types: Horizontal basal cells (quiescent) and globose basal cells (active)
Microvillar Cells
- Chemoreceptive cells of unknown function
- Sparse distribution throughout epithelium

Bowman's Glands

Serous glands in lamina propria
Function: Secrete mucus containing odorant-binding proteins
Ducts: Open onto epithelial surface

Olfactory Transduction

Odorant Receptor Proteins

G-protein coupled receptors (GPCRs)
~400 functional genes in humans (largest gene family)
One receptor type per neuron (monogenic expression)
Broad tuning: Each receptor responds to multiple odorants

Signal Transduction Cascade

Odorant binding to receptor protein
G-protein activation (Golf - olfactory specific)
Adenylyl cyclase activation (type III)
cAMP increase
Cyclic nucleotide-gated channel opening
Na+ and Ca2+ influx
Depolarization and action potential generation
Ca2+-activated Cl- channels amplify response

Adaptation Mechanisms

Receptor desensitization
cAMP phosphodiesterase activation
Ca2+/calmodulin-dependent adaptation

Central Olfactory Processing

Olfactory Bulb

Glomeruli: Spherical neuropil regions (~2,000 in humans)
- Convergence: ~25,000 ORNs of same type → 25 mitral/tufted cells
Mitral Cells: Primary output neurons
Tufted Cells: Secondary output neurons
Periglomerular Cells: Local interneurons
Granule Cells: Lateral inhibition and contrast enhancement

Central Projections (Bypass Thalamus)

Piriform Cortex: Primary olfactory processing
Amygdala: Emotional associations
Entorhinal Cortex: Memory formation
Orbitofrontal Cortex: Conscious perception and integration

Vomeronasal System (Vestigial in Humans)

Vomeronasal Organ (Jacobson's Organ): Detects pheromones
Accessory Olfactory Bulb: Processes vomeronasal signals
Function: Important in many mammals, minimal in humans

Common Olfactory Disorders

Anosmia

Complete loss of smell
Causes: Upper respiratory infections, head trauma, neurodegenerative diseases
Congenital: Kallmann syndrome (with hypogonadism)

Hyposmia

Reduced ability to smell
Age-related: Gradual decline with aging
Temporary: During respiratory infections

Parosmia

Distorted smell perception
Post-viral: Common after COVID-19
Quality changes: Pleasant odors become unpleasant

Phantosmia

Phantom odors without external stimulus
Causes: Seizures, migraines, psychiatric conditions

The Tongue and Taste

Anatomical Structure

Tongue Anatomy

Intrinsic Muscles: Change tongue shape (superior/inferior longitudinal, transverse, vertical)
Extrinsic Muscles: Change tongue position (genioglossus, hyoglossus, styloglossus, palatoglossus)
Innervation:
- Motor: Hypoglossal nerve (CN XII)
- Sensory: Trigeminal (CN V), facial (CN VII), glossopharyngeal (CN IX)

Lingual Papillae

Fungiform Papillae
- Location: Anterior 2/3 of tongue
- Number: ~200-400
- Taste Buds: 3-5 per papilla
- Shape: Mushroom-like
Circumvallate Papillae
- Location: V-shaped row at tongue base
- Number: 7-12
- Taste Buds: 100-300 per papilla (50% of all taste buds)
- von Ebner's Glands: Serous glands washing taste pores
Foliate Papillae
- Location: Lateral tongue edges
- Structure: Parallel folds
- Taste Buds: Well-developed in children, regress with age
Filiform Papillae
- Location: Entire tongue surface
- Function: Mechanical (no taste buds)
- Structure: Keratinized, conical projections

Taste Buds

Structure

Location: Within papillae epithelium
Shape: Barrel-shaped, 50-100 μm tall
Taste Pore: Apical opening to oral cavity
Number: ~10,000 in young adults (decreases with age)

Cell Types

Type I Cells (Dark Cells)
- Function: Support and taste bud maintenance
- Features: Dense cytoplasm, wrap around other cells
- Percentage: ~50-60% of taste bud cells
Type II Cells (Light Cells)
- Function: Sweet, bitter, and umami detection
- Features: G-protein coupled receptors
- Percentage: ~20-30% of taste bud cells
Type III Cells (Intermediate Cells)
- Function: Sour detection, some salt
- Features: Voltage-gated ion channels, synapses with nerves
- Percentage: ~15-20% of taste bud cells
Type IV Cells (Basal Cells)
- Function: Stem cells for taste bud renewal
- Turnover: Taste cells replaced every 7-10 days

Taste Transduction

Basic Taste Qualities

Sweet

Receptors: T1R2+T1R3 heterodimer
Ligands: Sugars, artificial sweeteners
Transduction: G-protein (gustducin) → PLC → IP3 → Ca2+ release → depolarization

Umami (Savory)

Receptors: T1R1+T1R3 heterodimer
Ligands: L-glutamate, nucleotides (IMP, GMP)
Transduction: Similar to sweet pathway

Bitter

Receptors: T2R family (~25 different receptors)
Ligands: Alkaloids, toxins, bitter compounds
Transduction: G-protein pathway → Ca2+ release
Function: Protective against potentially harmful substances

Sour

Stimulus: H+ ions (acid)
Mechanisms:
- Direct H+ entry through ion channels
- H+ blockade of K+ channels
Cells: Primarily Type III cells

Salt

Primary: Na+ through epithelial sodium channels (ENaC)
Secondary: Other mechanisms for different salts
Cells: Type III cells and possibly others

Signal Transmission

Type II Cells: Release ATP as neurotransmitter
Type III Cells: Form conventional synapses, release serotonin and GABA
Purinergic Signaling: ATP activates P2X receptors on nerve fibers

Gustatory Pathways

Peripheral Innervation

Facial Nerve (CN VII): Anterior 2/3 via chorda tympani
Glossopharyngeal Nerve (CN IX): Posterior 1/3 and circumvallate papillae
Vagus Nerve (CN X): Few taste buds in pharynx and epiglottis

Central Processing

Medulla: Nucleus tractus solitarius (gustatory nucleus)
Pons: Parabrachial nucleus
Thalamus: Ventral posterior medial nucleus
Cortex: Primary gustatory cortex (insula and frontal operculum)

Common Taste Disorders

Ageusia

Complete loss of taste
Rare condition
Causes: Severe nerve damage, certain medications

Hypogeusia

Reduced taste sensitivity
Common with aging
Causes: Medications, dry mouth, zinc deficiency

Dysgeusia

Altered taste perception
Metallic or bitter taste common
Causes: Medications, chemotherapy, infections

Burning Mouth Syndrome

Chronic burning sensation
Often affects taste perception
Multifactorial etiology

The Skin and Touch

Skin Structure

Epidermis

Layers (superficial to deep):

Stratum Corneum: Dead, keratinized cells
Stratum Lucidum: Clear layer (thick skin only)
Stratum Granulosum: Keratohyalin granules
Stratum Spinosum: Desmosomes connect cells
Stratum Basale: Mitotic activity, melanocytes

Dermis

Papillary Layer: Loose connective tissue with dermal papillae
Reticular Layer: Dense irregular connective tissue
Contents: Blood vessels, nerves, hair follicles, glands

Hypodermis (Subcutaneous Layer)

Adipose tissue and loose connective tissue
Insulation and energy storage
Anchors skin to underlying structures

Mechanoreceptors

Slowly Adapting (SA) Receptors

SA-I: Merkel's Discs

Location: Epidermis and hair follicles
Receptive Field: Small (2-4 mm diameter)
Function: Fine spatial discrimination, texture, Braille reading
Innervation: Aβ fibers
Adaptation: Slowly adapting to sustained pressure

SA-II: Ruffini Endings

Location: Deep dermis and subcutaneous tissue
Receptive Field: Large and diffuse
Function: Skin stretch, hand conformation, finger position
Innervation: Aβ fibers
Sensitivity: Lateral skin stretch and joint movement

Rapidly Adapting (RA) Receptors

RA-I: Meissner's Corpuscles

Location: Dermal papillae (especially fingertips, lips)
Receptive Field: Small (2-4 mm diameter)
Function: Light touch, texture, slip detection
Innervation: Aβ fibers
Frequency: Optimal response 20-50 Hz

RA-II: Pacinian Corpuscles

Location: Deep dermis, subcutaneous tissue, fascia
Receptive Field: Large (can cover entire hand)
Function: Vibration detection (200-300 Hz), tool use
Structure: Onion-like lamellated capsule
Innervation: Single Aβ fiber

Thermoreceptors

Cold Receptors

Nerve Fibers: Aδ and C fibers
Temperature Range: 15-35°C
Peak Sensitivity: ~25°C
Adaptation: Slow adaptation to constant temperature

Warm Receptors

Nerve Fibers: C fibers
Temperature Range: 30-45°C
Peak Sensitivity: ~40°C
Distribution: Less numerous than cold receptors

Molecular Basis

TRP Channels: Transient receptor potential ion channels
TRPM8: Cold and menthol receptor
TRPV1: Heat and capsaicin receptor (>43°C)
TRPV2, TRPV3, TRPV4: Various temperature ranges

Nociceptors (Pain Receptors)

Types Based on Fiber Type

Aδ Nociceptors

Myelinated fibers: Fast conduction (5-30 m/s)
Pain Type: Sharp, pricking, well-localized
Activation: Mechanical and thermal stimuli
Function: First pain, protective withdrawal

C Nociceptors

Unmyelinated fibers: Slow conduction (0.5-2 m/s)
Pain Type: Burning, aching, poorly localized
Activation: Mechanical, thermal, chemical stimuli
Function: Second pain, tissue damage signaling

Types Based on Stimulus

Mechanical Nociceptors

High-threshold mechanoreceptors
Activation: Intense pressure, pinprick, crushing

Thermal Nociceptors

Heat: >45°C (TRPV1, TRPV2)
Cold: <15°C (TRPA1)

Polymodal Nociceptors

Multiple stimuli: Mechanical, thermal, chemical
Most common type of nociceptor
C fibers predominantly

Chemical Mediators

Prostaglandins: Sensitize nociceptors
Substance P: Neurotransmitter and inflammatory mediator
Bradykinin: Potent pain mediator
Histamine: Itch and inflammation

Somatosensory Pathways

Dorsal Column-Medial Lemniscal Pathway

Function: Fine touch, vibration, proprioception

First-order neurons: Dorsal root ganglia → dorsal columns
Second-order neurons: Nucleus gracilis/cuneatus → medial lemniscus
Third-order neurons: VPL thalamus → primary somatosensory cortex

Spinothalamic Pathway

Function: Pain, temperature, crude touch

First-order neurons: Dorsal root ganglia → dorsal horn
Second-order neurons: Decussate → lateral/anterior spinothalamic tract
Third-order neurons: VPL thalamus → somatosensory cortex

Somatosensory Cortex

Primary (S1): Postcentral gyrus, somatotopic organization
Secondary (S2): Posterior parietal cortex, bilateral representation
Homunculus: Disproportionate representation based on sensitivity

Common Touch and Pain Disorders

Mechanical Sensitivity Disorders

Allodynia: Pain from normally non-painful stimuli
Hyperalgesia: Increased pain from painful stimuli
Hypoesthesia: Decreased touch sensation
Anesthesia: Complete loss of sensation

Neuropathic Pain

Peripheral neuropathy: Diabetes, chemotherapy
Central pain: Stroke, spinal cord injury
Complex regional pain syndrome: Chronic pain with autonomic changes

Temperature Sensitivity Disorders

Thermal hyperalgesia: Increased pain from temperature
Cold allodynia: Pain from mild cooling
Thermal hypoesthesia: Reduced temperature sensation

Nervous System Integration

Sensory Processing Hierarchy

Levels of Processing

Receptor Level: Transduction of stimuli
Circuit Level: Local processing and feature detection
Perceptual Level: Integration and interpretation

General Principles

Parallel Processing: Multiple pathways process different aspects simultaneously
Hierarchical Organization: Simple to complex feature detection
Plasticity: Experience-dependent changes in neural responses
Attention: Top-down modulation of sensory processing

Central Nervous System Structures

Brainstem

Medulla

Gustatory nucleus (taste)
Cochlear nuclei (hearing)
Vestibular nuclei (balance)

Pons

Superior olivary complex (sound localization)
Trigeminal nuclei (facial sensation)

Midbrain

Superior colliculus (visual reflexes, eye movements)
Inferior colliculus (auditory processing)

Thalamus (Sensory Relay)

VPL: Somatosensory (body)
VPM: Somatosensory (face), taste
LGN: Visual processing
MGN: Auditory processing
Note: Olfaction bypasses thalamus

Cerebral Cortex

Primary Sensory Areas

V1: Primary visual cortex (occipital lobe)
A1: Primary auditory cortex (temporal lobe)
S1: Primary somatosensory cortex (parietal lobe)
Gustatory: Insula and frontal operculum
Olfactory: Piriform cortex

Association Areas

Visual: V2, V3, V4, V5/MT (motion)
Auditory: Secondary auditory areas
Multisensory: Superior temporal sulcus, posterior parietal cortex

Sensory Integration

Multisensory Processing

Convergence zones: Areas receiving multiple sensory inputs
Temporal binding: Synchronization of neural activity
Cross-modal plasticity: One sense compensating for another

Attention and Consciousness

Selective attention: Focusing on relevant sensory information
Sensory gating: Filtering of irrelevant stimuli
Binding problem: Integration of features into unified percepts

Memory and Learning

Sensory memory: Brief retention of sensory information
Perceptual learning: Improvement with experience
Cross-modal associations: Linking different sensory modalities

Clinical Correlations

Diagnostic Approaches

Functional Testing

Vision

Visual acuity charts (Snellen, LogMAR)
Visual field testing (perimetry)
Color vision testing (Ishihara plates)
Ophthalmoscopy and slit-lamp examination

Hearing

Audiometry (pure tone, speech)
Tympanometry (middle ear function)
Otoacoustic emissions (cochlear function)
Vestibular testing (electronystagmography, rotary chair)

Smell and Taste

Scratch-and-sniff tests (University of Pennsylvania Smell Identification Test)
Taste threshold testing
Electrogustometry

Touch and Pain

Two-point discrimination
Vibration testing (tuning fork, vibrometer)
Temperature discrimination
Pain threshold assessment
Quantitative sensory testing (QST)

Imaging Studies

MRI: Detailed soft tissue imaging, functional MRI for brain activity
CT: Bone and dense tissue visualization
Ultrasound: Real-time imaging of eye structures
OCT (Optical Coherence Tomography): High-resolution retinal imaging
PET/SPECT: Metabolic and functional brain imaging

Vision

Presbyopia: Loss of accommodation starting ~40 years
Cataract formation: Lens opacity increases with age
Macular degeneration: Leading cause of blindness in elderly
Glaucoma risk: Increases significantly with age
Pupil size: Becomes smaller (senile miosis)

Hearing

Presbycusis: Age-related hearing loss, especially high frequencies
Hair cell loss: Progressive loss of cochlear hair cells
Central processing: Reduced speech discrimination in noise
Tinnitus: More common with aging

Smell and Taste

Olfactory decline: Significant reduction after age 60
Taste bud reduction: Gradual loss throughout life
Medication effects: Polypharmacy affects taste/smell
Dry mouth: Reduced saliva affects taste perception

Touch and Pain

Mechanoreceptor loss: Reduced density with aging
Vibration sensitivity: Decreased, especially in feet
Pain threshold: May increase with age
Temperature sensitivity: Reduced discrimination ability

Genetic Disorders

Vision

Color Blindness

X-linked: Red-green color blindness (8% males, 0.5% females)
Types: Protanomaly/Protanopia (L-cone), Deuteranomaly/Deuteranopia (M-cone)
Rare: Tritanomaly/Tritanopia (S-cone), complete achromatopsia

Inherited Retinal Diseases

Retinitis pigmentosa: Progressive rod-cone dystrophy
Leber congenital amaurosis: Severe early-onset blindness
Stargardt disease: Juvenile macular degeneration
Usher syndrome: Combined hearing and vision loss

Hearing

Congenital Hearing Loss

Connexin mutations: Gap junction proteins, most common genetic cause
Waardenburg syndrome: Hearing loss with pigmentation changes
Pendred syndrome: Hearing loss with thyroid enlargement
Alport syndrome: Hearing loss with kidney disease

Smell

Congenital Anosmia

Kallmann syndrome: Anosmia with hypogonadotropic hypogonadism
CHARGE syndrome: Multiple congenital anomalies including anosmia

Systemic Diseases Affecting Senses

Diabetes Mellitus

Diabetic retinopathy: Leading cause of blindness in adults
Neuropathy: Affects touch, pain, and temperature sensation
Taste changes: Delayed wound healing affects taste bud regeneration

Hypertension

Hypertensive retinopathy: Retinal vascular changes
Stroke risk: Can affect any sensory processing area

Autoimmune Diseases

Multiple Sclerosis

Optic neuritis: Inflammation of optic nerve
Sensory symptoms: Numbness, tingling, altered sensations
Central processing: Demyelination affects sensory pathways

Sjögren's Syndrome

Dry eyes: Reduced tear production
Dry mouth: Affects taste perception
Neuropathy: Peripheral sensory involvement

Infections

Viral Infections

COVID-19: Anosmia and dysgeusia common symptoms
Herpes zoster: Can affect trigeminal nerve (facial sensation)
Cytomegalovirus: Can cause retinitis in immunocompromised

Bacterial Infections

Otitis media: Middle ear infection affecting hearing
Meningitis: Can damage cranial nerves

Pharmaceutical Effects

Ototoxic Medications

Aminoglycosides: Damage to hair cells
Loop diuretics: High-dose can cause hearing loss
Chemotherapy: Cisplatin, carboplatin cause hearing loss
Aspirin: High doses can cause tinnitus and hearing loss

Medications Affecting Vision

Chloroquine/Hydroxychloroquine: Retinal toxicity
Corticosteroids: Can increase intraocular pressure
Digitalis: Can cause color vision changes (yellow tinting)

Medications Affecting Taste/Smell

ACE inhibitors: Metallic taste, altered smell
Antibiotics: Metallic taste common
Chemotherapy: Severe dysgeusia
Antihistamines: Dry mouth affects taste

Occupational and Environmental Hazards

Noise-Induced Hearing Loss

Mechanism: Damage to cochlear hair cells
Prevention: Hearing protection, noise reduction
Industries: Construction, manufacturing, military, music
Characteristics: Initially affects 4000 Hz frequency

Chemical Exposures

Solvents: Can affect multiple sensory systems
Heavy metals: Lead, mercury can cause neuropathy
Industrial chemicals: Various effects on sensory organs

Radiation Effects

Ionizing radiation: Cataract formation, retinal damage
UV radiation: Photokeratitis, macular damage
Laser exposure: Retinal burns

Emergency Conditions

Acute Vision Loss

Central Retinal Artery Occlusion

Presentation: Sudden, painless, severe vision loss
Appearance: Cherry-red spot on macula
Treatment: Ocular massage, hyperbaric oxygen (limited window)

Acute Angle-Closure Glaucoma

Symptoms: Severe eye pain, headache, nausea, halos around lights
Signs: Red eye, fixed mid-dilated pupil, corneal edema
Treatment: Immediate pressure reduction, laser iridotomy

Retinal Detachment

Symptoms: Flashing lights, floaters, curtain-like vision loss
Types: Rhegmatogenous, tractional, exudative
Treatment: Urgent surgical repair

Acute Hearing Loss

Sudden Sensorineural Hearing Loss

Definition: >30 dB loss in <72 hours
Treatment: High-dose corticosteroids within 2 weeks
Prognosis: 1/3 recover completely, 1/3 partially, 1/3 no recovery

Acoustic Trauma

Causes: Explosive noise, gunshots, loud music
Prevention: Immediate removal from noise source
Treatment: Corticosteroids may help if given early

Rehabilitation and Assistive Technologies

Visual Impairment

Low vision aids: Magnifiers, telescopes, electronic devices
Orientation and mobility: White cane training, guide dogs
Braille: Tactile reading system
Technology: Screen readers, voice recognition

Hearing Impairment

Hearing aids: Amplification for mild-moderate loss
Cochlear implants: Electronic hearing for severe-profound loss
Assistive listening devices: FM systems, infrared systems
Communication: Sign language, lip reading

Balance Disorders

Vestibular rehabilitation: Exercise-based therapy
Canalith repositioning: Treatment for BPPV
Balance training: Fall prevention programs

Future Directions and Research

Gene Therapy

Leber congenital amaurosis: FDA-approved gene therapy (Luxturna)
Inherited hearing loss: Gene therapy trials ongoing
Stem cell therapy: Potential for regenerating sensory cells

Artificial Sensory Devices

Artificial retina: Electronic implants for blindness
Cochlear implants: Continued improvements in technology
Tactile substitution: Converting visual/auditory to tactile signals

Neuroplasticity Research

Cross-modal plasticity: How senses compensate for each other
Perceptual learning: Training to improve sensory function
Brain stimulation: Enhancing sensory processing

Summary and Key Concepts

Essential Points for Study

Transduction mechanisms are specific to each sensory modality but follow similar principles
Specialized cells in each organ convert environmental energy into neural signals
Central processing involves multiple levels from brainstem to cortex
Integration of sensory information creates our perception of the environment
Clinical assessment requires understanding of normal function and common pathologies
Age-related changes affect all sensory systems but to varying degrees
Systemic diseases often have sensory manifestations that aid in diagnosis
Prevention and early intervention are crucial for maintaining sensory function