PBI288 - Final review

Transduction

Transduction

Process of changing stimulus ( energy, force, chemical...) from the environment into an electrochemical signal for the nervous system; Requires appropriate receptors & biochemical process in receptors that activate neurons

Sensory receptor

Specialized type of cell that responds to environmental stimulation (photoreceptors, cutaneous touch receptors)

Cell membrane receptor

Specialized type of protein on a cell that responds to biochemical activation (ionotropic receptors, metabotropic receptors)

Receptor Potential

Slow, moderate change in electrical state of a cell ( passive change, EPSP or IPSP)

Action Potential

Rapid, large change in electrical state of a cell (“all or none“ event, active propagation)

Summarize how activation of photoreceptors in the retina is transmitted to the lateral geniculate nucleus (LGN) in the thalamus

• Photoreceptors in retina activated by light

• Signals transmitted from photoreceptors to bipolar cells then ganglion cells

• Ganglion cells form optic nerve, carry signals to brain

• Signals reach LGN in thalamus

• Within LGN signals undergo processing

• Processed signals relayed to primary visual cortex in occipital lobe

Compare/contrast two types of photoreceptors in the human eye

Cones: most prevalent in central retina; found in fovea; sensitive to moderate-high levels of light; provide info about hue; provide excellent acuity.

Rods: most prevalent in peripheral retina; not found in fovea; sensitive in low levels of light; provide only monochromatic info; provide poor acuity.

Describe how differences in light-sensitive receptor proteins contribute to colour blindness

• Colour blindness results from malfunction/absence of one or more types of cone cells in retina

• Differences in opsin genes, which code for cone cell proteins, contribute to colour blindness

• Variations in opsin can lead to: missing/non-functioning red, green or blue cone cells & reduced sensitivity/altered spectral sensitivity of cone cells

• Types of colour blindness: red-green (protanopia & deuteranopia)& blue-yellow (tritanopia)

• Affected individuals may have trouble distinguishing certain colours/perceive them differently

• Colour blindness can impact daily tasks such as interpreting traffic signals/selecting ripe fruits

Summarize how information from left & right visual fields is directed to the right & left brain hemispheres

• Each eye receives input from both left & right visual fields

• Optic nerves from both eyes meet at optic chiasm (some fibers cross to opposite side, some continue straight)

• Fibers carrying information from nasal (inner) retina of each eye cross at optic chiasm to opposite side of brain

• Fibers carrying information from temporal (outer) retina of each eye stay straight on to same side of brain

• Visual information from left visual field of both eyes processed in right hemisphere of brain & visual information from right visual field of both eyes processed in left hemisphere of brain

• Arrangement ensures that each hemisphere processes information from both visual fields, enabling integrated perception of entire visual field in each hemisphere

Anatomy of the eye

Properties of light

• Hue → specific/dominant wavelength (colour)

• Brightness → intensity of light (amount of light present)

• Saturation → “purity“ of light, richness of colour (just one wavelength vs many other wavelengths)

Binocular vision

• Each eye has slightly different view of a given object, because of small difference between eyes

• Merging images helps us perceive depth

Rhodopsin

Photopigment in rods that responds to light

Opsin

Photopigment in cones

Photopigment

• Made up of opsin (protein) & retinal (lipid)

• Light strikes photopigment molecules & splits it into opsin & retinal components

“Dark current”

In darkness, photoreceptors release glutamate at synapses with bipolar neurons

Receptive fields

• Represents part of visual field that it responds to (changes its firing rate)

• Constituency of cells that provide info to retinal ganglion cell MP (think of it as government)

Organization of receptive fields

• On-centre/off-surround cells: likes light in middle of its receptive field

• Off-centre/on-surround cells: likes light around perimeter of its receptive field

Lateral Geniculate Nucleus

• Bilateral, multilayered structure (6 )

• Each layer receives specific types of info from retina

• Layers distinguished by cell size ( magnocellular = large, parvocellular =small, koniocellular = tiny)

Optic chiasm

• Splitter

• Axons coming from medial/nasal part of retina cross to opposite hemisphere at optic chiasm

• Axons coming from lateral/peripheral part of retina do not cross

• Info from left visual field is directed to right LGN (& right visual cortex)

From retina to brain

1. RGC axons leave eye (optic nerve)

2. Optic chiasm

3. 1st synapse in LGN in thalamus

4. 2nd synapse in primary visual cortex (V1)

V1: organization

• Striate cortex

• 6 layers: inputs from LGN enter at layer 4 of V1, inputs from ipsilateral & contralateral eyes kept separate in layer 4

• Organized into modules or small ‘columns‘ of cortex

V1: representation of visual field

• Retinotopic map preserved in V1 & fovea processed by proportionally more cells than in any other area of retina

List the characteristics of visual information processed by cells in V1 (primary visual cortex)

1. Orientation: most neurons in V1 sensitive to specific orientations of light-dark information in its receptive field, sensitive= more neuron firing when light/dark boundary oriented at specific angle

2. Spatial frequency: changes in brightness, refers to # of times area of visual information shifts (light→dark→light→dark), high frequency information= lots of small details & large objects with clear edges/contours, low frequency information=visual scenes with large objects & blurry/ not too much detail

3. Retinal disparity: binocular cells become very active when image of an object appears on slightly different areas of left & right retinas (difference in location between eyes), crossed-disparity=objects close to us, uncrossed-disparity= objects far away from us

4. Colour: third stage of colour processing occurs in V1→ colour-sensitive cells in blobs

5. Movement

V1: modules

• Each module contains a tiny region of all 6 layers of V1 ( 0.5mm diameter)

• Each module ‘sees‘ information from tiny part of the retina

• Cells within single module specialize for orientation (180°), left-right eye (binocular & monocular preference, disparity gives info about distance)

• 4 colour blobs per module

• Movement

• Spatial frequency

Extrastriate visual cortex

• Areas of visual cortex outside V1 (visual association cortex,~ 25% of human cerebral cortex)

• Each area specialized for aspects of visual information

• Receive info from V1→process →pass on information to higher areas of extrastriate cortex ( area V4→colour processing, area V5→movement)

• V2 & V3 cells→similar properties to V1 (retinotropic organization, cells selective for angle/direction of motion, cortical magnification, most are binocular)

• Ventral vs dorsal stream

Visual processing

• ~ 25-30% of human cerebral cortex involved in visual processing

Ventral stream (extrastriate visual cortex)

• ”what“ pathway

• Allows for object recognition

• P pathway, some K pathway (colour, texture, detail)

• Signals forwarded to parts of inferior temporal lobes

• Vision for recognition (1. Cells in each region respond to more complex stimuli 2. Cases of IT cortex damage→agnosias 3. Very large receptive fields)

Dorsal pathway (extrastriate visual cortex)

• ”where/how“ pathway

• Allows for locating objects in space, perceiving motion relative to other objects, making actions in relation to object

• M & K pathway inputs

• Vision for action pathway (1.Cells in V5 direction-selective 2.Cases of V5 parietal cortex damage→akinetopsia, apraxias)

• From V1, info sent to parts of posterior parietal lobes & dorsal temporal lobes

• Different regions specialized for identifying low-detail, movement-related visual info

Visual agnosia

• Difficulty recognizing/interpreting visual information despite perfect vision

• Often caused by damage to brain's visual processing areas

• Various types affecting different aspects of visual perception

• Object agnosia: difficulty recognizing objects

• Prosopagnosia: difficulty recognizing faces

• Spatial agnosia: difficulty perceiving spatial awareness

IT cortex

• Face recognition region

• Fusiform face area (FFA) in inferior temporal lobe activated in primates when viewing faces

• Reduced FFA activity associated with poor face recognition (propropagnosia)

Akinetopsia

• Motion blindness (stroboscopic vision→only snapshots of visual scenes, no continuous movement)

• Caused by damage to V5 area (medial superior temporal lobe)

Ablation

• Destruction of tissue

• Electrolytic: electrode used to burn small area of tissue

• Non-selective: all tissue at site destroyed

Exitotoxic ablation/lesions

• Injection of excitatory agonist drugs directly into brain tissue

• Selective way → only dentrites, cell bodies that have receptors for drug are affected

Temporary ablation/lesions

• Injection of inhibitory agonists like muscimol (gaba-a agonist)

• Way of inhibiting regional activity, drug effect washes out with time

Light microscopy

• Resolution up to 1500x

Electron microscopy

• Resolution up to the nanoscale (x10^-9)

• Synapses & individual organelles visible

Scanning electron microscopy

• Resolution up to the nanoscale (x10^-9)

• Gives 3D view

Tracers

• Used to identify projections by injection

• Anterograde: dendrites→axons (eg. Phaseolus vulgaris leucoagglutinin)

• Retrograde: axons→dendrites (eg. Fluoro-gold/ hydroxystilbamidine)

Computerized axial tomography (CAT or CT)

• Pass x-rays through head

• Shows tissue density

Magnetic resonance imaging (MRI)

• Uses magnets & radio waves to determine tissue density in brain

Diffusion tensor imaging (DTI)

• Form of MRI

• Tracks water movement along myelinated axons to show where white matter bundles are

Positron emission tomography (PET)

• Radioactive glucose injected into bloodstream

• Brain tissue that is active uses more glucose

Functional MRI (fMRI)

• Detects small changes in oxygen use in active brain areas

• No radioactivity needed

• Regions of tissue that are active require more oxygen & more oxygenated blood flows to active brain regions

• Measures blood oxygenation level-dependent (BOLD) levels

Microdialysis

• Measures release of neurotransmitters within brain region

• Dialysis probe inserted into a brain region

• Substances in extracellular fluid can diffuse across membrane into tube

• Analyze fluid sample for content

Electrophysiological recordings

• Listen in on cell firing patterns from single cell all the way up to multiple brain regions at once

• Use electrodes to directly stimulate cells/specific parts of brain

• Lateral hypothalamic stimulation: animals will self-administer stimulation to electrodes near lateral hypothalamus (activate dopamine cells in ventral tegmental area)

Transcranial magnetic stimulation (TMS)

• Generates mild magnetic fields to trigger changes in activity of localized brain regions

• Used for research & therapeutic purposes

• Allows for non-invasive manipulation of neural activity

• Device held near skull surface, pulsed current through device creates magnetic field which alters neural activity in tissue below the skull

• Vs TDCS → pulsed current directly through

Deep brain stimulation (DBS)

• Brain stimulation techniques increasingly used for therapeutic purposes in humans

• Implantation of chronic electrodes for some movement disorders (Parkinson's), severe depression, epilepsy

Optogenetics

• Activate parts of brain without electricity or drugs

• Provides selective way of activating/inhibiting specific neurons by “injecting“ light into brain

• Infect cells with viruses so they make “light-sensitive” receptor protein

• Channel Rhodopsin 2→activated by blue light→ opens Na+ channel

• Halorhodopsin→activated by yellow/orange light → open Cl- channel

Genetic methods

• Manipulating gene expression allows targeting of specific proteins in nervous system

• Multiple approaches (genetic mutation→delete gene, add extra copies, modify it; RNA manipulations→block production of proteins from gene transcription)

• Manipulation/mutation: targeted deletion of a gene (‘knockout‘) can tell us about role a gene may normally have

• Crispr-CAS9, knockouts/knock-ins, upregulation|downregulation, cross-breeding

Experimental controls

• An equivalent experience of all steps of a manipulation/treatment except for step that is thought to have an effect

• For surgery→’ sham’ surgery

• For drug injections→vehicle injection (eg. Saline)

Recognize different ways of lesioning brain tissue

• Electrolytic

• Excitotoxic

• Temporary

Recognize different ways of imaging/recording activity of live brain tissue

• Microscopy: light microscopy, electron microscopy, scanning electron microscopy

• Tracers: anterograde, retrograde

• Brain imaging: CAT, CT, MRI, fMRI, DTI, PET

Recognize different ways of manipulating of live brain tissue

• Lateral hypothalamic stimulation

• Transcranial magnetic stimulation

• Transcranial direct current stimulation

• Deep brain stimulation

• Optogenetics

• Genetic manipulation/mutation

Physical properties of sound

• Produced by objects that vibrate & set molecules of air into motion

• Vibrations cause molecules of air to move in waves that travel away from object

• Frequency, measured in hertz (Hz), cycles/sound

• Hz determines pitch of sound (high→soprano, low→bases)

• Loudness/volume reflects how ‘big‘ sound waves were

• Timbre is complexity of sound waves

Anatomy of auditory system

1. Outer

2. Middle

3. Inner

Outer ear

• Pinna funnels sound waves into auditory canal

• Tympanic membrane (eardrum) at end of canal

Middle ear

• Tympanic membrane→ossicles: hammer (malleus), anvil (incus), & stirrup (stapes) bones

• Stirrup pushes on oval window membrane

Inner ear

• Oval window→opening into cochlea

• Fluid filled→ fluid movement creates travelling wave in membranes inside cochlea

• Specialized membranes inside

Organ of Corti

• Region where sound wave transduction happens

• Basilar membrane (bottom)

• Tectorial membrane (tap)

• Hair cells (outer & inner)→attached to basilar membrane, some touch the tectorial membrane above

Hair cells (auditory system)

• Sound receptors

• Inner & outer rows of hair cells on basilar membrane

Sound transduction

• Each hair cell contains cilia

• Side-by-side, attached to one another by flexible tips links (movement of one cilium pushes/pulls the ones around us)

• Site where tip links attach to each cilium called insertional plaque

• Insertional plaques contain ion channels

• Movement of cilia opens ion channels in insertionnal plaques

• Ion channels open→ ions flow→electrical changes inside hair cell (receptor potential)

Pitch

• 2 mechanisms used in cochlea: Place coding & Rate coding

• Place coding: high frequency (high pitches) move only part of basilar membrane closer to oval window

• Rate coding: hair cells on basilar membrane match firing rate to frequency of sound ( 100 Hz → hair cells fire 100 times/second), rate of cell firing in auditory nerve gives us info about sound pitch

• Evidence shows that both place & rate coding happen in cochlea (place coding→higher pitches, rate coding→ lower pitches)

Auditory pathway in brain

• Auditory nerve activated

• To medulla (cochlear nucleus)

• To tectum in midbrain (inferior colliculus)

• To thalamus (medial geniculate nucleus)

• To primary auditory cortex (temporal lobe)

• Each hemisphere ‘hears‘ from both ears, but ‘hears more‘ from contralateral ear (left ear→right temporal lobe)

Causes of deafness

1. Conduction deafness: ears do not conduct sound to nervous system

2. Sensorineural deafness: problems with structures that convert sound vibrations into neural activity

3. Central deafness: hearing loss caused by brain damage (variable forms)

   Causes of deafness in aging:

4. Presbycusis: most common form of a hearing loss in older adults, hearing loss greater for high pitched sounds

5. Hair cell loss: noise, genetic variation, some medications (aspirin & certain antibiotics)

6. Loss of blood supply to ear: heart disease, high blood pressure, diabetes

7. Damage to middle ear (membrane or bones conducting sounds)

Treating deafness

• Cochlear implants used to treat deafness due to hair cell loss (sensorineural or central deafness)

• Electrical currents stimulate the auditory nerve

Complex sound processing

• Hearing in cerebral cortex occurs through 2 pathways (anterior & posterior)

• Anterior pathway: ‘what‘ pathway, helps us recognize what sounds are, judge if familiar/ unfamiliar

• Posterior pathway: ‘where‘ pathway, helps us identify where sounds are coming from

• Evidence shows that these system are plastic

Music/pitch perception

• Musicians have larger neural response to pitch info than non-musicians (shown for both musical & speech sounds)

• Musician’s brains look different & respond differently to music (activation of motor regions when listening to familiar piece)

Taste: physical stimulus

• Taste involves perception of chemical compounds (tastants) dissolved in medium (not same as flavour)

• Humans perceive only a limited range of tastants (each may have own adaptive/survival value, responses to each can change with age/experience/cultural influences)

Taste (anatomy)

• Tastant receptors found in taste buds on tongue, mouth & throat (on tongue, taste buds located on sides of papillae)

• No tastant-specific ‘map‘ of tongue

Taste: transduction

• A taste bud is a cluster of receptor cells (constantly regenerating)

• Each cell extends microvilli into ‘taste pore‘ (gap between papillae)

• Microvilli contain ion channels/receptors

• Tastants bind to receptors→triggering transduction

• Change in electrical state of taste cells, synapse with sensory nerve fibers in tongue

• Each taste cell responds to only one type of tastant

Taste: trajectory

• Taste signals carried to brain via cranial nerves

• Brainstem: nucleus of solitary tract

• Ventral posteriomedial thalamus→primary gustatory cortex= frontal cortex (insula) →orbitofrontal cortex

• Ventral posteriomedial thalamus→somatosensory cortex

What affects the sensitivity of our sense of taste?

• Absolute thresholds very low for bitter tastants

• Higher for sweet tastants

• Combinations can modify perceived intensity of each

• Interactions with other senses (smell)

• A factory triggered by airborne molecules: may be inhaled directly from outside air or pushed up through back of mouth/throat into naval cavity

Smell: anatomy

• OIfactory receptor cells are bipolar cells

• Axons project up through cribiform bone ( axons terminate in glomerulus, small clustered region of axons)

• Mitral cells in olfactory bulb, brain tissue above cribiform bone (mitral cells send their dendrites into glomerulus, axons of mitral cells form olfactory tract into brain)

Olfactory epithelium

Olfactory epithelium

• Layer of tissue at top of nasal cavity

• Receptor cells embeddedin epithelium

• Cilia project into mucosal layer

Smell: transduction

• We can distinguish between 1000s of different smells

• In humans,~350 different olfactory receptors made (all metabotropic)

• Each receptor can bind to more than one type of odorant molecule

• Each odorant can bind to more than one type of receptor

• Individual smells created by unique patterns of receptor activation

What affects our sensitivity in our sense of smell?

• Type of odorant (different absolute thresholds for different odorants)

• Developmental differences (hyposmia-decreased ability to smell-more common in older age)

• Sex differences (women > men, small differences for some odorants)

• Experience ( adaptation, rapid sensitivity decreases with prolonged exposure to odorants)

• Influenced by attention (less adaptation to noxious smells)

• Recognition thresholds influenced by familiarity/experience (also affected by verbal abilities, greater vocabulary = greater recognition)

Multimodal nature of flavours

• Vision: visual can affect how flavour is perceived (eg. White wine with tasteless/odourless red dye described by oenologists as red wine), reported sweetness enhanced by red; saltiness by white, congruence between visual cues & smells, flavours affect judgements of un/pleasantness

• Hearing: ’sonic chip’ experiment (higher crispness, freshness ratings with louder, high-frequency sounds), high-frequency sounds increase ’fizziness’ ratings of carbonated drinks, high levels of background noise may reduce perceived saltiness

Hedonic value of flavours (like/dislike)

• Orbital frontal cortex is key

• Activity in OFC correlates with motivation to consume, ratings of pleasantness of foods

• Activity in OFC correlates with expectation of quality & with rated ‘liking‘ of wine & with believed price

Vestibular system

• Allows perception of ‘linear translational movements’ in space & rotational movements of head

• Sense of balance

• Keep head in an upright position

• Adjusts eye movement to compensate for head movements

• 2 parts: semicircular canals & vestibular sacs

Semicircular canals

• Orientation of head space

• 3 fluid-filled canals

• Movement of head causes movement of endolymph

• Ampulla at base of each canal

• Cupula within each ampulla contains hair cells

• Movement of cupula causes movement of hair cells (bending of hair cells causes receptor potential, receptor potential activates auditory cranial nerve

Vestibular sacs

• Utricle & saccule → balance & equilibrium

• 2 fluid-filled compartments next to semicircular canals (tissues on sides of sacs contain layer of hair cell receptors - otoconia on top of this layer)

• Movement of fluid within sacs pushes on ocotonia, pushes hair cell cilia

• Receptor potential activates auditory cranial nerves

Somatic perception

• Different aspects to somatic perception (perception of the body) → 1. Cutaneous perception 2. Proprioception & kinesthesia

• 3 types of info received through cutaneous perception: touch, temperature, pain

Touch

• Different types of touch (tactile) receptors give us different types of touch sensations → pressure, vibration, stretching, movement, textures

• Tactile receptor types differ in:

1. What type of stimulation they respond to best

2. How fast they adapt (stop responding to stimulation)

3. Which type of skin they are found in (hairy vs glabrous) & where

4. Receptive field size

Cutaneous perception

• 4 key types of ‘encapsulated mechanoreceptors‘, or tactile receptors

1. Merkel's discs

2. Meissner's corpuscle

3. Ruffini's ending

4. Pacinian corpuscle

Merkel's discs

• Touch

• Fingertips, lips, tongues

• Pressure info

• Form perception, edges, fine details

• Slow adapting

• Small receptive fields

Meissner's corpuscle

• Fingertips, lips, tongue

• Pressure & movement info

• Form perception, texture

• Fast adapting

• Small receptive fields

Ruffini's ending

• Deeper, in hypodermis

• Stronger pressure

• Stretch info

• Slow adapting

• Large receptive fields

Pacinian corpuscle

• Deeper, in hypodermis

• Strong, vibrating pressure or movement

• Texture info

• Large receptive fields

Temperature perception

• Temperature receptors in skin respond to changes in skin temperature from 34°C (normal)

• ’Transient receptor potential‘ (TPR) receptor family

Transient receptor potential (TPR)

• Cold sensors in skin closer to epidermis, warmth sensors located more

• Warmth sensors located more deeply

• Each TPR receptor type has a ’preferred‘ range of temperature

• Some can be activated by chemical chemical compounds

Nociception

• Pain perception = ‘nociception‘, noxious or harmful

• Several types of pain receptors in skin on free nerve endings

• TRPV1, TRPV2 receptors activated by strong heat chemical compounds

• At least 4 types of pain receptors in skin

1. High-threshold mechanoreceptors

2. TRPV1 receptors: heat (burns) & chemicals (eg. Capsaicin), burning sensation

3. TRPA1 receptors: chemicals that cause inflammation

4. TRPM3 receptors: activated by very high h eat ( around > 45°C → higher TRPV1), axons of nerves large diameter (myelinated)

• Activation of receptors→A delta or C fibers in spinothalamic path (special kind of sodium channel found in these axons: Nax 1.7)

• Cingulate cortex activity correlates with amount of pain reported

• Cingulate activity decreases when painkillers (analgesics) or placebos taken & reported pain decreases

Somatosensory pathways

• Somatosensory receptors (touch, temperature, pain) activated

• From receptors in body below head, axons enter CNS via spinal nerves (dorsal root ganglia)

• From face & head, via cranial nerves (mostly trigeminal nerve)

• Route in CNS depends on type of info carried: dorsal column (touch) & spinothalamic (pain, temperature)

• Both pathways send axons to: ventral posterior thalamus→primary somatosensory cortex

Primary somatosensory cortex

• Somatic map of body in parietal cortex

• Bigger parts → more sensitive to touch/temperature /pain perception

Somatic nerves

• Tactile information is carried by different types of nerves than temperature or pain info

What happens if transduction pathway mutated (Nax 1.7)

• Ashlyn Blocker → “ pain is a gift, she doesn't have it”

• Inherited erythromelalgia “man on fire”syndrome →hyperactivation of nerves carrying pain signals to spinal cord

Pain perception

• Pain information also activates other regions of cerebral cortex: anterior cingulate cortex (ACC) & insular cortex (frontal lobe)

• Different parts to experience pain:

1. Touch, sensory → primary somatosensory cortex

2. Emotional response → ACC & insular cortex

Touch & pain interaction

• Touch, pressure can sometimes suppress pain, at least temporarily

• “Gate Theory“ of pain perception

Gate Theory