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The Visual Pathway and Lesion-Field Defects

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Structures in the Pathway (top to bottom)

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Key Anatomical Principle: The Decussation Rule

• Nasal (medial) hemiretina fibers cross at the optic chiasm
• Temporal (lateral) hemiretina fibers stay ipsilateral
• After the chiasm, each optic tract carries visual information from the contralateral visual field of both eyes
• The left cortex "sees" the right visual field, and vice versa

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Lesion Sites and Visual Field Defects

Lesion A - Left Optic Nerve (before the chiasm)

• Defect: Complete blindness in the left eye only (monocular blindness / amaurosis)
• Right eye is normal
• This is because no decussation has occurred yet
• Key viva point: The Marcus Gunn (RAPD - relative afferent pupillary defect) will be positive in the left eye

Lesion B - Optic Chiasm (central, e.g. pituitary tumor)

• Defect: Bitemporal hemianopia - loss of the outer (temporal) visual fields of both eyes
• This is a heteronymous hemianopia (defects are on opposite sides of the vertical meridian)
• Caused by destruction of the crossing nasal fibers from both retinas
• Classic cause: pituitary macroadenoma growing superiorly; also craniopharyngioma, meningioma of tuberculum sellae, aneurysm of anterior circle of Willis
• Key viva point: This is the ONLY lesion that produces bitemporal hemianopia - "Only a lesion of the optic chiasm causes true bitemporal hemianopia" (Bradley and Daroff's Neurology)

Lesion C - Left Optic Tract (pretectal region, post-chiasm)

• Defect: Right homonymous hemianopia - loss of right half of visual field in BOTH eyes
• Homonymous = same side of the vertical meridian in both eyes
• Often incongruous (asymmetric between the two eyes) because fibers from both eyes are not yet tightly interdigitated
• The left tract carries: temporal fibers from left eye + nasal fibers from right eye (both serving the right visual field)
• Key viva point: Retrochiasmal lesions always produce homonymous defects. The more anterior in the retrochiasmal pathway, the more incongruous the defect.

Lesion D - Left Occipital Cortex / Geniculocalcarine Tract

• Defect: Right homonymous hemianopia with macular sparing
• Notice in the diagram that a central island of vision is preserved on the right side for both eyes
• Macular sparing occurs because the macular cortex at the occipital pole has dual blood supply from both the MCA and PCA - occlusion of the PCA (most common cause of occipital infarct) spares the pole
• Defect is congruous (identical in both eyes) because fibers are tightly packed at the cortex
• Key viva point: Macular sparing = occipital cortex lesion (most commonly PCA territory infarct). If the macula is NOT spared, it is more likely to be an optic tract or radiation lesion.

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Summary Table for Viva

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Additional Viva Points

1. Meyer's loop: The inferior optic radiation fibers loop anteriorly through the temporal lobe. A temporal lobe lesion causes a contralateral superior quadrantanopia ("pie in the sky" defect).
2. Parietal lobe lesions: Affect inferior optic radiations, causing contralateral inferior quadrantanopia ("pie on the floor").
3. Pupillary reflex: The pupillary light reflex pathway branches off at the pretectal region (before the LGB). So retrogeniculate (cortical) lesions - even causing complete hemianopia - do NOT affect the pupillary reflex.
4. RAPD testing: A lesion of the optic nerve or optic tract (pre-LGB) can cause a relative afferent pupillary defect (RAPD), detectable with the swinging flashlight test.
5. Pituitary tumor growth pattern: As a pituitary adenoma enlarges superiorly, it first compresses the inferior chiasmal fibers, causing upper bitemporal quadrantanopia first, then progressing to full bitemporal hemianopia.

• Ganong's Review of Medical Physiology, Figure 10-14
• Adams and Victor's Principles of Neurology, 12th Ed - Lesions of the Chiasm, Optic Tract, and Geniculocalcarine Pathway
• Bradley and Daroff's Neurology in Clinical Practice - Box 16.2 General Rules of Visual Field

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Viva Discussion - All Charts (Guyton & Hall Reference)

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CHART 1 - Sarcomere Structure (Slide 11)

• 1 - Z Line (Z disk): Cross-filamentous proteins that anchor actin filaments; the sarcomere lies between two successive Z disks
• 2 - Sarcomere: The functional unit of muscle, from one Z disk to the next (~2 micrometers at full contraction)
• 3 - Thick Myosin Filament: Each myofibril contains ~1500 myosin filaments; forms the A band (dark, anisotropic to polarized light)
• 4 - Thin Actin Filament: Each myofibril contains ~3000 actin filaments; forms the I band (light, isotropic to polarized light)

• The A band = myosin + overlapping actin ends (dark)
• The I band = actin filaments only (light)
• The H zone = region of myosin not overlapped by actin
• Titin (connectin) molecules hold myosin filaments in place, act as molecular springs
• Maximal force is generated at sarcomere length ~2.2 µm (optimal overlap)
• Cross-bridges project from myosin and interact with actin to produce contraction (sliding filament mechanism)

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CHART 2 - Convergence (Slide 13)

• Modifies the activity of the postsynaptic neuron - the output depends on the summation of all inputs
• Allows spatial summation - simultaneous firing of multiple inputs can reach threshold even if no single input can
• Allows temporal summation - repeated inputs from the same source can accumulate
• Convergence is the neural basis for integration - the CNS receives and integrates information from many sources before deciding on a response
• Example: A motor neuron receives converging inputs from the corticospinal tract, vestibulospinal tract, reticulospinal tract, and sensory afferents

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CHART 3 - Taste Bud (Slides 14 & 15)

• A - Taste Pore: The small opening at the surface of the taste bud where dissolved substances (tastants) enter
• B - Taste Receptor Cell: Specialized receptor cells with microvilli (taste hairs) projecting through the pore; contain receptor proteins that bind taste molecules
• C - Basal Cell: Stem cells that regenerate taste receptor cells approximately every 10 days
• D - Afferent Nerve: Sensory fibers that transmit taste signals to the brain (CN VII, IX, X)

• Taste buds are located mainly on the tongue (circumvallate, fungiform, foliate papillae), also on soft palate, pharynx, epiglottis
• 5 primary taste sensations: Sweet, sour, salty, bitter, umami (glutamate)
• Taste signals travel via:
  • CN VII (chorda tympani) - anterior 2/3 of tongue
  • CN IX (glossopharyngeal) - posterior 1/3 of tongue
  • CN X (vagus) - epiglottis and pharynx
• All converge on the nucleus tractus solitarius (NTS) in the medulla, then thalamus, then gustatory cortex (parietal/insular)

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CHART 4 - Facilitated Diffusion (Slide 17)

1. The transported molecule approaches the carrier protein
2. It enters the pore and binds to a specific receptor/binding site
3. A conformational change occurs in the carrier protein
4. The pore opens on the opposite side and the molecule is released

• Simple diffusion: rate increases linearly with concentration
• Facilitated diffusion: rate approaches a maximum (Vmax) - becomes saturated when all carrier proteins are occupied

• GLUT4 (in skeletal muscle, adipose, heart) is stimulated by insulin, increasing glucose uptake by 10-20 fold

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CHART 5 - Na+-K+ ATPase Pump (One of the slides)

• 3 Na⁺ out (from intracellular cytoplasm to ECF)
• 2 K⁺ in (from ECF into cytoplasm)
• For every cycle: 1 ATP is hydrolyzed to ADP + Pi
• The protein has ATPase activity on its inner cytoplasmic portion
• Ouabain (cardiac glycoside) blocks the K⁺ binding site on the outside, inhibiting the pump

• B = K⁺ binding site (extracellular)
• Subunits 1-5 = structural components of the alpha and beta subunits of the pump
• α = catalytic subunit (contains ATPase, Na⁺/K⁺ binding sites)

• The pump keeps intracellular [Na⁺] low and [K⁺] high - essential for maintaining resting membrane potential
• Digitalis/Ouabain inhibits Na+-K+ ATPase → intracellular Na⁺ rises → Na⁺-Ca²⁺ exchanger works less efficiently → intracellular Ca²⁺ increases → increased force of myocardial contraction (positive inotropy)
• This is the mechanism by which digoxin treats heart failure

1. Maintains resting membrane potential (-70 mV)
2. Controls cell volume - prevents osmotic swelling and lysis
3. In nerve cells, 60-70% of total energy expenditure goes to this pump

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CHART 6 - Action Potential (Membrane Potential Graph)

• PS = Polarized State (Resting Membrane Potential = -70 mV)
• LR = Local Response / Local Excitatory State
• Firing Level = Threshold potential (~-55 mV)
• Phase 1 (box) = Stimulus period / rising phase begins
• Phase 2 (box) = Rising phase / Depolarization (Na⁺ rushes in; peak ~+35 mV)
• Phase 3 (box) = Falling phase / Repolarization (K⁺ rushes out)
• Phase 4 (box) = After-hyperpolarization / Undershoot (membrane more negative than resting, -70 mV)

• Absolute Refractory Period (ARP): During depolarization - Na⁺ channels are inactivated; NO stimulus can generate another AP
• Relative Refractory Period (RRP): During after-hyperpolarization - a STRONGER than normal stimulus can generate another AP

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CHART 7 - Olfactory Pathway (Diagram with OG, PG, Gr, M, T, CP)

• Gr = Granule cell (yellow star-shaped) - inhibitory interneurons
• OG = Olfactory Glomerulus - spherical synaptic complexes where olfactory nerve fibers synapse
• PG = Periglomerular cell - inhibitory interneurons surrounding glomeruli
• M = Mitral cell - primary output neurons of the olfactory bulb
• T = Tufted cell - secondary output neurons
• CP = Cribriform Plate - the bony sieve through which olfactory nerve filaments pass

1. Odorant molecules dissolve in nasal mucus → bind to olfactory receptor proteins on cilia of olfactory receptor neurons
2. Signal travels up olfactory nerve filaments (CN I) through the cribriform plate of the ethmoid bone
3. Synapses in olfactory glomeruli of the olfactory bulb
4. Mitral and tufted cells relay signals via the olfactory tract
5. Signals go to:
   • Prepyriform cortex and amygdala (for emotional/behavioral responses - no thalamic relay)
   • Thalamus → Orbitofrontal cortex (for conscious smell perception)

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CHART 8 - Long-Term Potentiation / Synaptic Plasticity (Last chart: Glu, NMDA, AMPA, retrograde messenger NO)

1. Weak stimulation: Glutamate activates AMPA receptors only → small depolarization
2. Strong/repeated stimulation: Sufficient depolarization removes Mg²⁺ block from NMDA receptor
3. NMDA receptor opens → Ca²⁺ floods into postsynaptic cell
4. Ca²⁺ activates Ca²⁺/calmodulin kinase, PKC, tyrosine kinase
5. These kinases trigger:
   • Insertion of new AMPA receptors into the synapse (making it more sensitive)
   • Production of retrograde messenger (likely Nitric Oxide, NO)
6. NO diffuses backward to the presynaptic terminal → enhanced neurotransmitter release in future stimulations
7. Result: The synapse is now potentiated - same input produces GREATER output

• LTP is the cellular mechanism of learning and memory (especially hippocampus)
• NMDA antagonists (like ketamine, MK-801) block LTP
• NMDA receptors require BOTH glutamate binding AND depolarization (coincidence detector)
• LTP can last hours to weeks - the basis of long-term memory storage

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1. ENDOCYTOSIS (Vesicle fusing with cell membrane → cytoplasm)

• A vesicle containing molecules approaches the cell membrane
• The vesicle progressively fuses with the membrane
• Contents are released into the cytoplasm

• Pinocytosis - ingestion of fluid/small molecules ("cell drinking")
• Phagocytosis - ingestion of large particles like bacteria ("cell eating")
• Receptor-mediated endocytosis - specific molecules bind surface receptors, membrane invaginates and internalizes them

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2. Na⁺-K⁺ ATPase PUMP (with Ouabain, heart failure)

• 3 Na⁺ are pumped OUT of the cell (cytoplasm → ECF)
• 2 K⁺ are pumped INTO the cell (ECF → cytoplasm)
• 1 ATP is hydrolyzed to ADP + Pi per cycle
• The protein has intrinsic ATPase activity on its cytoplasmic surface

• B = K⁺ binding site (extracellular)
• 3 Na⁺ out / 2 K⁺ in = electrogenic ratio (net +1 charge out → contributes to membrane potential)
• Ouabain = cardiac glycoside that blocks the extracellular K⁺ binding site, inhibiting the pump

Ouabain/Digitalis inhibits Na⁺-K⁺ ATPase → intracellular Na⁺ rises → Na⁺-Ca²⁺ exchanger works less → intracellular Ca²⁺ increases → stronger cardiac contraction (positive inotropy)

1. Maintains resting membrane potential (-70 mV)
2. Controls cell volume (prevents osmotic swelling)
3. Nerve cells use 60-70% of their energy just for this pump

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3. OLFACTORY PATHWAY (OG, PG, Gr, M, T, CP)

1. Odorant → dissolves in nasal mucus → binds olfactory receptor proteins on receptor cell cilia
2. Signal travels via CN I through cribriform plate
3. Synapses in olfactory glomeruli in the olfactory bulb
4. Mitral & Tufted cells relay signals via the olfactory tract to:
   • Prepyriform cortex + Amygdala (emotion, behavior - NO thalamic relay)
   • Thalamus → Orbitofrontal cortex (conscious smell perception)

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4. Na⁺-K⁺ ATPase PUMP - Detailed Diagram (3Na out, 2K in, ATPase)

• This is primary active transport - energy from ATP is used directly
• The pump is electrogenic - creates a slight negative charge inside the cell
• 3 binding sites for Na⁺ on the intracellular face; 2 binding sites for K⁺ on the extracellular face
• ATPase activity is on the intracellular (cytoplasmic) portion
• When 3 Na⁺ bind inside and 2 K⁺ bind outside → ATPase is activated → ATP cleaved → conformational change → ions are transported

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5. ACTION POTENTIAL (Membrane potential graph, PS, LR, Firing level, Phases 1-4)

• PS = Polarized State = Resting Membrane Potential = -70 mV
• LR = Local Response / Local Excitatory State (subthreshold depolarization)
• Firing Level = Threshold potential = -55 mV (the point of no return)
• Box 1 = Stimulus period (resting state, before threshold)
• Box 2 = Depolarization - Na⁺ channels open, Na⁺ rushes IN; peak reaches +35 mV
• Box 3 = Repolarization - Na⁺ channels inactivate; K⁺ channels open, K⁺ rushes OUT
• Box 4 = After-hyperpolarization - K⁺ channels slow to close; membrane briefly more negative than resting (~-80 mV), then returns to -70 mV

• Absolute Refractory Period (ARP): During depolarization - Na⁺ channels are inactivated; NO new action potential can fire regardless of stimulus strength
• Relative Refractory Period (RRP): During after-hyperpolarization - a stronger than normal stimulus CAN fire another AP

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6. LONG-TERM POTENTIATION / SYNAPTIC PLASTICITY (NMDA, AMPA, NO, retrograde messenger)

1. Weak stimulation: Glutamate activates only AMPA receptors → small depolarization
2. Strong/repeated stimulation: Enough depolarization to dislodge Mg²⁺ block from NMDA receptor
3. NMDA opens → Ca²⁺ floods into postsynaptic neuron
4. Ca²⁺ activates kinases (CaM kinase, PKC, Fyn)
5. New AMPA receptors are inserted into the synapse → synapse is now more responsive
6. Retrograde NO diffuses to presynaptic terminal → enhanced glutamate release in future
7. Result: Same input now produces a greater output = the synapse is potentiated

• LTP is the cellular mechanism of learning and memory, especially in the hippocampus
• NMDA receptor acts as a coincidence detector - requires BOTH presynaptic glutamate release AND postsynaptic depolarization simultaneously
• NMDA antagonists (ketamine) block LTP and impair memory formation