LECTURE 8

Review of Lecture 7: Core Sensory Integration Concepts

Sample Questions and Logical Foundations

1. Sound Frequency Sensitivity Humans are particularly sensitive to sound frequencies in the range of $2 - 5\,kHz$ . This sensitivity is primarily related to human speech perception. While humans can detect a broader range, this specific peak in sensitivity aligns with the acoustic requirements for understanding spoken language.

2. Neural Encoding and Computation The statement "the brain computes (or encodes) a signal" refers to a specific biological correspondence: there is a direct relationship between a signal (or a specific property of that signal) and the differential activity of neurons within brain regions that constitute the relevant circuitry or pathway.

3. Sensory System True/False Comparisons

Transduction Mechanism: In auditory and vestibular systems, transduction occurs in specialized receptor cells which release neurotransmitters to affect the membrane potential of sensory neuron endings. However, this is NOT true for the somatosensory system.
Ion Channels: Both auditory and vestibular hair cells utilize a transduction mechanism mediated by mechano-sensitive ion channels.
Visual Exception: The visual system is unique among sensory systems discussed because the conversion of signal energy (light) into an electrical signal produces inhibition (hyperpolarization) of the receptor cells rather than excitation.
Waveform Following: It is false that the receptor potential of hair cells follows the stimulus waveform at all sensitive frequencies; this ability is limited by the physical and physiological properties of the cells at higher frequencies.

Lecture 8: The Visual System

Fundamentals of Light and Vision

The visual system detects changes in luminance, which is approximately the detection of emitted light across various spectrums:

Ultraviolet (UV): $10 - 400\,nm$
Visible Light: $380 - 740\,nm$
Infrared: From $780\,nm$ and above.

Visible light exhibits a dual nature, possessing properties of both waves and particles. It is emitted and absorbed in tiny "packets" or quanta known as photons. The primary properties includes:

Intensity: Perceived as brightness.
Propagation Direction: The path light travels.
Frequency/Wavelength: Perceived as color.

Historical and Anatomical Overview

Historical Context: Research by René Descartes ( $1596 - 1650$ ) confirmed that the eye functions as a Camera obscura. This principle, illustrated in James Ayscough’s work ( $1755$ ), demonstrates that images are projected inverted onto the retinal surface through the pupil and lens.

The Retina: A part of the nervous system forming the neural portion of the eye. It contains:

Photoreceptors: Specialized neurons (rods and cones) that transduce sensory signals.
Bipolar Cells: Interneurons that relay signals.
Retinal Ganglion Cells (RGCs): Cells that transmit signals toward central targets in the brain via their axons.

Key Retinal Landmarks:

Fovea: The area on the retina where the fixation point of the visual field falls. It is the anatomical substrate for visual acuity.
Optic Disk: The region where blood vessels enter and retinal axons exit the eye. This area lacks photoreceptors, resulting in a "blind spot" insensitive to light.
Visual Field: The part of the visual space seen by an eye. Images are projected inverted onto the retina.

Visual Pathways and Projections

Retinal Hemifields and Crossing:

The binocular visual field consists of two symmetrical hemifields.
Nasal Retina: Axons from the nasal portion of each retina cross at the optic chiasm.
Temporal Retina: Axons from the temporal portion do not cross.
Optic Tract: Each tract contains axons from both eyes representing the contralateral visual field. For example, the right optic tract represents the left visual field.

Major Central Pathways:

Primary Visual Pathway: RGCs $\rightarrow$ Optic Nerve $\rightarrow$ Optic Tract $\rightarrow$ Thalamus (Lateral Geniculate Nucleus, LGN) $\rightarrow$ Striate (Primary Visual) Cortex. Function: Perception of visual signals.
Retinohypothalamic Pathway: Mediated by "light sensitive" melanopsin-expressing RGCs (mRGCs) $\rightarrow$ Optic Nerve $\rightarrow$ Optic Tract $\rightarrow$ Hypothalamus (Suprachiasmatic Nucleus, SCN). Function: Regulation of circadian rhythms and homeostatic functions.
Pretectum Pathway: RGCs $\rightarrow$ Optic Nerve $\rightarrow$ Optic Tract $\rightarrow$ Pretectum $\rightarrow$ Edinger-Westphal nucleus $\rightarrow$ Ciliary ganglion $\rightarrow$ Pupillary constrictor muscles. Function: Pupillary light reflex.
Superior Colliculus Pathway: RGCs $\rightarrow$ Optic Nerve $\rightarrow$ Optic Tract $\rightarrow$ Superior Colliculus. Function: Saccadic eye movements (orienting the movement of head and eyes).

Phototransduction: Turning Light into Electricity

Photoreceptor Anatomy

Outer Segments: Composed of membranous discs containing photopigments.
Inner Segments: Contain the cell body and form synaptic contacts with bipolar and horizontal cells.
Photopigments: Transmembrane chromoproteins (opsins) coupled to G-proteins. They contain chromophores that absorb light.

The Molecular Mechanism of Phototransduction

Photoreceptors generate graded receptor potentials rather than action potentials. Unlike most sensors, they hyperpolarize in response to stimuli.

Absorption: A photon is absorbed by the chromophore retinal (part of the opsin complex) in the disc membrane.
Configuration Change: Retinal changes from the cis to the trans configuration.
G-Protein Activation: This conformational change activates the G-protein complex, transducin.
Enzyme Activation: Transducin's alpha subunit with GTP activates Phosphodiesterase (PDE).
cGMP Hydrolysis: PDE hydrolyzes cGMP, drastically reducing its concentration in the cell.
Channel Closing: The reduction of cGMP causes cGMP-gated $Na^+$ / $Ca^{2+}$ channels to close.
Hyperpolarization: The cell hyperpolarizes ( $V_m$ shifts from approx $-40\,mV$ in the dark to $-65\,mV$ in the light).
Neurotransmitter Modulation: In the dark, there is constitutive release of glutamate via L-type $Ca^{2+}$ channels. Light causes these channels to close, leading to a reduction in glutamate release.

Comparison of Rods and Cones

Rods:
- High sensitivity to light (can respond to a single photon).
- Low resolution/acuity.
- One photopigment (rhodopsin).
- Specialized for night (scotopic) vision.
Cones:
- Low sensitivity to light (require approx $100$ photons).
- High resolution/acuity.
- Three types of opsins (S, M, and L).
- Specialized for day (photopic) vision and color vision.
- Density is highest in the fovea (center of the macula).

Color Vision and Deficiencies

Human color vision is mediated by three types of cones differentially sensitive to different wavelengths:

S (Short): Blue.
M (Medium): Green.
L (Long): Red.

Color Blindness:

Protanopia: Loss of long-wavelength-sensitive (L) cones; difficulty discriminating red and green.
Deuteranopia: Loss of medium-wavelength-sensitive (M) cones; difficulty discriminating red and green.

Retinal Circuitry and Receptive Fields

Information Flow

Vertical: Photoreceptors $\rightarrow$ Bipolar Cells $\rightarrow$ Ganglion Cells.
Lateral: Mediated by Horizontal cells and Amacrine cells (modulatory interneurons).

ON and OFF Center Ganglion Cells

Every point on the retina is analyzed by overlapping ON- and OFF-center cells.

ON-Center Cells: Activated by an increase in luminance in the center of the receptive field.
OFF-Center Cells: Activated by a decrease in luminance in the center of the receptive field.

Mechanism (Glutamate Receptor Dependent):

Light Response: Light hyperpolarizes the photoreceptor, decreasing glutamate release.
ON-Bipolar Cell: Expresses inhibitory mGluR6 receptors. Decreased glutamate releases them from inhibition, causing depolarization and activation of the ON-ganglion cell.
OFF-Bipolar Cell: Expresses excitatory AMPA (and NMDA) receptors. Decreased glutamate causes hyperpolarization (loss of excitation), inhibiting the OFF-ganglion cell.

Surround Inhibition

Horizontal cells provide inhibitory GABAergic input. When light hits the "surround" of a receptive field, horizontal cells modulate the central response, often reducing the firing rate of the ganglion cell even if the center is illuminated.

Classification of RGCs (M, P, K)

Magnocellular (M) Cells: Large receptive fields, fast conduction, transient responses. Do not transmit color (receptive field centers and surrounds have same cone classes).
Parvocellular (P) Cells: Smaller receptive fields, slower conduction, sustained responses. Convey color (centers and surrounds have different cone classes: S, M, or L).
Koniocellular (K) Cells: Fine-caliber axons; might contribute to color vision via S-cone input.

Central Visual Processing

Lateral Geniculate Nucleus (LGN)

Laminar Organization: Segregated layers for inputs from each eye.
Monocular Neurons: Individual LGN neurons receive input from only one eye.
Development: Eye-specific refinement depends on spontaneous spontaneous retinal waves and BDNF support from LGN neurons.

Primary Visual Cortex (Striate Cortex / Layer 17)

Anatomy: Notable for the Stria of Gennari (a dense myelinated band of axons in Layer 4).
Layer 4: Receives the densest projections from the LGN; neurons here remain monocular.
Columnar Architecture:
- Ocular Dominance Columns: Stripes of neurons responding preferentially to one eye. Convergence for binocular vision occurs in layers outside of Layer 4 (e.g., Layers 2/3).
- Orientation Columns: Neurons tuned to specific edge orientations. Neurons along a radial axis share preferences; those along a tangential axis shift preferences progressively.
Visuotopic (Topographic) Organization: The fovea is represented over a disproportionately large area of the visual cortex compared to the periphery.

Specialized Retinal Projections

Melanopsin-Expressing Retinal Ganglion Cells (mRGCs)

Unlike most RGCs, these are intrinsically photosensitive.
They contain melanopsin and depolarize in response to light.
They project to the Suprachiasmatic Nucleus (SCN) for circadian regulation and the Olivary Pretectal Nucleus (OPN) for the pupillary light reflex.
Rods mediate transient pupil constriction, while mRGCs maintain steady-state constriction.

Superior Colliculus and Saccades

Receives visual input and sends commands to brainstem gaze centers.
Initiates saccades: rapid, active eye movements that shift the view to interesting features of a visual scene several times per second.

Chemosensory Systems

Olfactory System

Components: Olfactory epithelium, Cribriform plate, Olfactory bulb (OB), Olfactory tract.
Transduction:
1. Odorants bind to G-protein coupled receptors ( $G_{olf}$ ).
2. Alpha subunit activates Adenyl cyclase III.
3. $cAMP$ is generated, opening cAMP-gated channels to depolarize the cell.
4. $Ca^{2+}$ -dependent $Cl^-$ channels open to provide additional depolarization.
Glomeruli: Sites in the OB where Olfactory Receptor Neurons (ORNs) that express the same gene converge on Mitral cells.
Mitral Cells: Relay olfactory info to the brain (Pyriform cortex, Amygdala, Entorhinal cortex). The system bypasses the thalamus for primary projections.

Gustatory System

Components: Papillae $\rightarrow$ Taste buds $\rightarrow$ Taste cells.
Transduction: Categories (Sweet, Sour, Salty, Bitter, Umami) are encoded by distinct receptor proteins. Release of ATP or neurotransmitters activates ionotropic receptors ( $P2X$ ) on primary sensory neurons.
Pathway: Receptor cells $\rightarrow$ Cranial nerve ganglia $\rightarrow$ Solitary tract nucleus $\rightarrow$ Thalamus (VPMN) $\rightarrow$ Gustatory Cortex.

Sample Questions: Lecture 8

1. Phototransduction Hyperpolarization The hyperpolarization of cones is mediated by the closing of nucleotide (cGMP)-gated channels.

2. Bipolar Cell Polarity What determines if a center bipolar cell depolarizes or hyperpolarizes in response to light in the center is the type of postsynaptic glutamate receptors at the synapse between the photoreceptor and the bipolar cell (mGluR6 vs. AMPA).

3. Optic Chiasm Crossing The crossing ensures that each optic tract conveys visual information from both eyes, effectively representing the contralateral visual field in each tract.