nervous system + neurobiology and behaviour

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neurons

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1

neurons

specialised cells of the nervous sytem that carry electrical impulses

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myelin sheath

improves the conduction speed of electrical impulses along the axon, but require additional space and energy

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resting potential

the difference in charge across the membrane when a neuron is not firing (-70 mV), the inside of the neuron is more negative

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maintaining resting potential

  • The sodium-potassium pump is a transmembrane protein that actively exchanges sodium and potassium ions (antiport)

  • It expels 3 Na+ ions for every 2 K+ ions admitted

  • electrochemical gradient whereby the cell interior is relatively negative compared to the extracellular environment

  • The exchange of sodium and potassium ions requires the hydrolysis of ATP (it is an energy-dependent process)

  • proteins inside the nerve fibers are negatively charged

  • some potassium ions are able to diffuse out of the cell

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action potential

the rapid changes in charge across the membrane that occur when a neuron is firing

  • depolarization, repolarization and a refractory period

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depolarisation

  • In response to a signal initiated at a dendrite, voltage gated sodium channels open within the membrane of the axon

  • As Na+ ions are more concentrated outside of the neuron, the opening of sodium channels causes a passive influx of sodium

  • if the threshold potential is reached, all sodium channels open

  • The influx of sodium causes the membrane potential to become more positive (depolarisation)

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repolarisation

Repolarisation refers to the restoration of a membrane potential following depolarisation

  • Following an influx of sodium, voltage gated potassium channels open within the membrane of the axon

  • As K+ ions are more concentrated inside the neuron, opening potassium channels causes a passive efflux of potassium

  • The efflux of potassium causes the membrane potential to return to a more negative internal differential (repolarisation)

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refractory period

The refractory period refers to the period of time following a nerve impulse before the neuron is able to fire again

  • In a normal resting state, sodium ions are predominantly outside the neuron and potassium ions mainly inside (resting potential)

  • Following depolarisation (sodium influx) and repolarisation (potassium efflux), this ionic distribution is largely reversed

  • Before a neuron can fire again, the resting potential must be restored via the antiport action of the sodium-potassium pump

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all or none principle

the neuron will only fire if the threshold potential is reached

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oscilloscopes

scientific instruments that are used to measure the membrane potential across a neuronal membrane

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myelin

a mixture of protein and phospholipids that is produced by glial cells (Schwann cells in PNS; oligodendrocytes in CNS)

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saltatory conduction

  • In myelinated neurons, the action potentials ‘hop' between the gaps in the myelin sheath called the nodes of Ranvier

  • This results in an increase in the speed of electrical conduction by a factor of up to 100-fold

  • The disadvantage of myelination is that it takes up significant space within an enclosed environment

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chemical transfer accross synapses

  1. action potential reaches the axon terminal

  2. voltage gated Ca2+ channels open

  3. Ca2+ eters the pre-synaptic neuron

  4. Ca2+ signals to neurotransmitter vesicles

  5. neurotransmitter released via exocytosis

  6. neurotransmitter binds to receptors

  7. signal initiated by post-synaptic neuron

  8. neurotransmitters released into the synapse are either recycled (by reuptake pumps) or degraded (by enzymatic activity)

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neurotransmitter

chemical messengers released from neurons and function to transmit signals across the synaptic cleft

  • Neurotransmitters are released in response to the depolarisation of the axon terminal of a presynaptic neuron

  • Neurotransmitters bind to receptors on post-synaptic cells and can either trigger (excitatory) or prevent (inhibitory) a response

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acetylcholine

  • activates a post-synaptic cell by binding to one of two classes of specific receptor (nicotinic or muscarinic)

  • broken down into its two component parts by the synaptic enzyme acetylcholinesterase (AChE)

    • AChE is either released into the synapse from the presynaptic neuron or embedded on the membrane of the post-synaptic cell

    • The liberated choline is returned to the presynaptic neuron where it is coupled with another acetate to reform acetylcholine

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blocking of synaptic transmission at cholinergic synapses in insects

  • Neonicotinoid pesticides are able to irreversibly bind to nicotinic acetylcholine receptors and trigger a sustained response

  • Neonicotinoid pesticides cannot be broken down by acetylcholinesterase, resulting in permanent overstimulation of target cells

  • Insects have a different composition of acetylcholine receptors which bind to neonicotinoids much more strongly → leads to paralysis

  • Hence, neonicotinoids are significantly more toxic to insects than mammals, making them a highly effective pesticide

    • neonicotinoids have been successfully used to protect crops from pest species

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disadvantages of neonicotinoid pesticides

  • Neonicotinoid use has been linked to a reduction in honey bee populations (bees are important pollinators within ecosystems)

  • Neonicotinoid use has also been linked to a reduction in bird populations (due to the loss of insects as a food source)

  • Consequently, certain countries (including the European Union) have restricted the use of neonicotinoid pesticides

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graded potentials

small changes in membrane potentials as a result of the opening of ligand gated ion channels on the target cells

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Excitatory neurotransmitters (e.g. noradrenaline)

cause depolarisation by opening ligand-gated sodium or calcium channels

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Inhibitory neurotransmitters (e.g. GABA)

cause hyperpolarisation by opening ligand-gated potassium or chlorine channels

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embryogenesis

development of a fully-formed organism from a fertilised egg

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neurulation

formation of a neural tube in embryonic chordates

  • Cells located in the outer germ layer (ectoderm) differentiate to form a neural plate

  • The neural plate then bends dorsally, folding inwards to form a groove flanked by a neural crest

  • The infolded groove closes off and separates from the neural crest to form the neural tube

  • The neural tube will elongate as the embryo develops and form the central nervous system (brain and spinal cord)

  • The cells of the neural crest will differentiate to form the components of the peripheral nervous system

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process of neurulation in Xenopus

  1. notochord dervied from mesoderm

  2. ectoderm differentiate to form the neural plate and neural plate borders

  3. neural plate folds inwards and downwards, the notochord is pushed down

  4. neural plate borders meet to form the neural crest

  5. closing of the neural tube

  6. separation of the neural crest from ectoderm

  7. the neural tube will eventually form the brain and the spinal cord

  8. the notochord degenerates and forms intervertebral discs

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neural crest cells will differentiate into…

the majority of the peripheral NS

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mesoderm will differentiate into…

somites, which will give rise to parts of the muscoskeletal system

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All tissues are derived from…

three initial germ layers (ectoderm, mesoderm, endoderm) formed via gastrulation

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spina bifida

a birth defect resulting in the incomplete closure of the neural tube (and associated vertebrae)

  • most commonly seen in the lumbar and sacral areas, as these are the regions where closure is slowest

  • spinal cord nerves exposed and prone to damage

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spina bifida cystica

a meningeal cyst forms (meningocele) which may include the spinal elements (myelomeningocele)

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results of severe cases of spina bifida

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gial cells

provide physical and nutritional support for the neurons – roughly 90% of nerve cells in the brain are glial cells

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neurogenesis

  • come from progenitor neuroblasts

    • neurons do not proliferate - they are post-mitotic

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progenitor cells are…

multipotent

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neural migration

  • glial guidance - glial cells may provide a scaffolding network along which an immature neuron can be directed to its final location

  • somal translocation - the neuron may form an extension at the cell’s perimeter and then translocate its soma along this length

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an immature nueron consists of…

a cell body (soma) containing a nucleus and cytoplasm

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how do axons grow from immature naurons?

in response to chemical stimuli from surrounding cells

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filipodia

motile growth filaments found on an axon’s growth cone tip

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growth of axons

  • Extension of these filipodia causes the expansion of the internal cytoskeleton within the growth cone – resulting in growth

  • The direction of this expansion is controlled by chemical stimuli released from surrounding cells

  • These cells may release chemoattractant signals (grow towards) or chemorepellant signals (grow away)

  • Using these molecular guidance signals, axon growth cones may navigate long distances to reach specific targets

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neural pruning

the loss of unused neurons (by removing excess axons and eliminating their synaptic connections)

  • Infant and adult brains typically have the same total number of neurons (roughly 100 billion neurons in total)

  • However infant brains form vastly more synaptic connections (approximately twice the number found in adult brains)

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purpose of neural pruning

to reinforce complex wiring patterns associated with learned behaviour

  • Pruning is influenced by environmental factors and is mediated by the release of chemical signals from glial cells

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neuroplasticity

the capacity for the nervous system to change and rewire its synaptic connections

  • enables individuals to reinforce certain connections (learning) or circumvent damaged regions

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Rerouting

creating re-establishing an existing nervous connection via an alternative neural pathway

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Sprouting

-the growth of new axon or dendrite fibres to enable new neural connections to be formed

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stroke

the sudden death of brain cells in a localised area due to inadequate blood flow, resulting in improper brain function

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ischemic strokes

result from a clot within the blood restricting oxygenation to an associated region of the brain

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ischemic strokes on a CT scan

dark regions

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hemorrhagic stroke

result from a ruptured blood vessel causing bleeding within a section of the brain

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hemorrhagic stroke on a CT scan

white region

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results of strokes

  • smptoms may be temporary if the brain is able to reorganise its neural architecture to restore function

  • Following a stroke, healthy areas of the brain may adopt the functionality of damaged regions

  • This capacity for the restoration of normal function is made possible due to the neuroplasticity of the brain

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how does the brain develop?

by the elongation and enlarging of the neural tube

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the anterior part of the neural tube will develop into…

the brain during cephalisation

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the remainder of the neural tube will develop into…

the spinal cord

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embryonic brain composition

forebrain, midbrain, hindbrain

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forebrain

cerebrum, thalamus

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midbrain

parts of brainstem

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hindbrain

pons, cerebellum, medulla oblongata

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external and internal section of the brain

  • The major external structures include the cerebral cortex, cerebellum and brainstem

  • Internal structures include the hypothalamus, pituitary gland and corpus callosum

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cerebral cortex

  • The cerebral cortex is an outer layer of tissue organised into two cerebral hemispheres and composed of four distinct lobes

  • The frontal lobe controls motor activity and tasks associated with the dopamine system (memory, attention, etc.)

  • The parietal lobe is responsible for touch sensation (tactility) as well as spatial navigation (proprioception)

  • The temporal lobe is involved in auditory processing and language comprehension

  • The occipital lobe is the visual processing centre of the brain and is responsible for sight perception

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cerebellum

  • The cerebellum appears as a separate structure at the base of the brain, underneath the cerebral hemispheres

  • It is responsible for coordinating unconscious motor functions – such as balance and movement coordination

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brainstem

  • The brainstem is the posterior part of the brain that connects to the spinal cord (which relays signals to and from the body)

  • The brainstem includes the pons, medulla oblongata (often referred to as the medulla) and the midbrain

  • The brainstem (via the medulla) controls automatic and involuntary activities (breathing, swallowing, heart rate, etc.)

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hypothalamus

  • The hypothalamus is the region of the brain that functions as the interface with the pituitary gland

  • As such, the hypothalamus functions to maintain homeostasis via the coordination of the nervous and endocrine systems

  • The hypothalamus also produces some hormones directly, which are secreted via the posterior pituitary (neurohypophysis)

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pituitary gland

  • The pituitary gland is considered the ‘master’ gland – it produces hormones that regulate other glands and target organs

  • The anterior lobe is called the adenohypophysis and secretes hormones such as FSH, LH, growth hormone and prolactin

  • The posterior lobe is called the neurohypophysis and secretes hormones such as ADH and oxytocin

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corpus callosum

  • The corpus callosum is a bundle of nerve fibres that connects the two cerebral hemispheres

  • It is the largest white matter structure in the brain, consisting of roughly 250 million axon projections

  • Damage to the corpus callosum can prevent information exchange between left and right hemispheres (split brain disorders)

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animal experiments

  • used to identify function by stimulating regions with electrodes or removing via lobotomy

  • limited by the differences between animal and human brains, making valid comparisons difficult

  • less ethical restrictions

  • developing treatments for MS

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fMRI

  • records changes in blood flow within the brain to identify activated areas

  • Oxygenated haemoglobin responds differently to a magnetic field than deoxygenated haemoglobin

  • These differences in oxygenation can be represented visually and reflect differences in the level of brain activity

  • non-invasive

  • diagnosing ADHD and dyslexia

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lesions

  • abnormal areas of brain tissue which can indicate the effect of the loss of a brain area

  • post-mortem analysis (autopsy) or via scans of the brain (CT scans or MRI)

  • Split brain patients have been used to identify specific roles of the left and right cerebral hemisphere

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autopsy

  • post-mortem examination of a corpse via dissection in order to evaluate causes of death

  • Cadavers who suffered from aphasia (language impairment) in life demonstrate damage to specific areas

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visual cortex

  • within the occipital lobe of the cerebrum and receives neural impulses from light-sensitive cells in the eyes

  • responsible for visual perception (sight)

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Broca’s area

  • the frontal lobe of the left cerebral hemisphere

  • Is responsible for speech production (if damaged, the individual cannot produce meaningful speech despite intending to)

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nucleus accumbens

  • involved in the pleasure reward pathway and is found within each cerebral hemisphere

  • secretes neurotransmitters responsible for feelings of pleasure (dopamine) and satiety (serotonin)

  • communicates with other centres involved in the mechanisms of pleasure, such as the ventral tegmental area (VTA)

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increasing the total area of human brains

  • by extensive folding (gyrification) to form wrinkled peaks (gyrus) and troughs (sulcus)

  • increases surface area without increasing volume – allowing the brain to fit within the cranium

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The extent of gyrification of the cerebral cortex is a reliable indicator of what?

potential cognitive capacity

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left hemisphere

  • sensory stimulus from the right side of the body

  • motor control (right side)

  • speech, language, comprehension

  • analysis and calculations

  • time and sequencing

  • recognition of words, letters, numbers

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right hemisphere

  • sensory stimulus from the left side of the body

  • motor control (left side)

  • creativity

  • spatial ability

  • context/perception

  • recognition of faces, places, objects

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sympathetic responses

  • Decreases salivary release and blood flow to the gut in response to swallowing

  • Increases ventilation rate and dilates airways in response to a reduction in blood pH (caused by increased levels of CO2)

  • Increases heart rate by raising the normal sinus rhythm of the pacemaker of the heart

  • glucose released

    • fight or flight

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parasympathetic responses

  • rest and digest

  • Increases salivary release and blood flow to the gut in response to swallowing

  • Lowers ventilation rate and constricts airways in response to an increase in blood pH (caused by lower levels of CO2)

  • Reduces heart rate (via vagus nerve) by lowering the normal sinus rhythm of the pacemaker of the heart

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the pupil reflex

Pupils constrict in bright light (to prevent overstimulation of photoreceptors) and dilate in dim light (to maximise light exposure)

  • In bright light, parasympathetic nerves trigger circular muscles to contract and cause the pupils to constrict

  • In dim light, sympathetic nerves trigger radial muscles to contract and cause the pupils to dilate

  • excess light can damage the retina

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brain death

the permanent absence of measurable activity in both the cerebrum and brainstem

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how is brain death determined

  • The pupil reflex is one autonomic test used to assess brain death – brain dead individuals will not exhibit a pupil reflex

  • The Glasgow Coma Scale uses multiple tests to determine the neurological health of someone with suspected brain injury

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encephalisation

the amount of brain mass relative to an animal's body mass

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how much energy does the brain consume

~20% of the body’s energy levels, despite making up only ~2% of the body’s mass

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why is energy needed in the brain?

  • Energy is needed to maintain a resting potential when neurons are not firing (Na+/K+ pump uses ATP)

  • Energy is used to synthesise large numbers of neurotransmitters to facilitate neuronal communication

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sensitivity

the ability of an organism to detect external and internal changes and respond accordingly

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receptors

detect changes as stimuli, and generate nerve impulses which are relayed to the brain and effector organs

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mechanoreceptor

  • movement

  • sound waves, touch, stretch, pressure

  • in ears, arteries, skin

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photoreceptor

  • light

  • visible spectrum (400-700 nm)

  • eyes - retina

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chemoreceptor

  • chemicals

  • pH, molecules, solutes

  • tongue, nose, tissues

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thermoreceptor

  • temperature

  • heat, cold

  • skin, hypothalamus

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structure of the eye

  • lens that separates the aqueous and vitreous humour (fluid-filled sacs

  • ciliary muscles that contract and relax to change the focus of the lens

  • iris that dilates and constricts to regulate the amount of light entering the eye via pupils

  • cornea lubricated by the conjunctiva - colourless layer that protect the exposed part of the eye

  • sclera, choroid, retina - the outermost to innermost layers of the internal eye surface

  • fovea - region of the retina in which vision is sharpest

  • optic nerve sends nerve signals from the retina to the brain

  • blind spot - at the back where there is no retina

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retina

the light-sensitive layer of tissue that forms the innermost coat of the internal surface of the eye

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how does light travel through the eye

  • Two types of photoreceptors (rods and cones) convert light stimuli into electrical nerve impulses

  • These nerve impulses are transmitted via bipolar cells to ganglion cells, whose fibres from the optic nerve tract

  • The photoreceptors line the rear of the retina (adjacent to the choroid), meaning light passes through the other cell layers

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human ear structure

  • pinna - the external ear

  • auditory canal in the outer ear channels sound waves to the tympanic membrane

  • ossicles - in the middle ear, transfer vibrations to the oval window

  • inner ear consists of the cochlea and semicircular canals, as well as a round window which dissipates vibrations

  • cochlea converts sound stimuli into electrical nerve impulses, which are transmitted via the auditory nerve to the brain

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photoperception

the mechanism of light detection (by the eyes) that leads to vision when interpreted by the brain

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rod cells

  • low light - they become bleached quickly in bright light

  • contain rhodopsin, which absorbs a range of wavelengths

  • monochromatic - do not differentiate between colours

  • abundant at the periphery of the retina and hence are responsible for peripheral vision

  • produce poorly resolved images as many rod cells synapse with a single bipolar neuron

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cone cells

  • bright light conditions (daylight vision) – they require more photons of light to become activated

  • different types of cone cells, each with a different pigment that absorbs a narrow range of wavelengths

  • differentiate between different colours (red, blue and green)

  • abundant at the centre of the retina (within the fovea) and hence are involved in visual focusing

  • produce well defined images as each cone cell synapses with a single bipolar neuron

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function of bipolar cells

transmit nerve impulses generated by rods and cones to ganglion cells

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function of ganglion cells

transport nerve impulses to the brain via long axonal fibers that form the optic nerve

  • Signals from ganglion cells may be sent to the visual cortex to form a composite representation of surroundings (i.e. sight)

  • Alternatively, signals may be sent to other brain regions to coordinate eye movements or maintain circadian rhythms

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what happens at the blind spot and why?

  • the brain interpolates details from the surrounding regions, such that individuals do not perceive a visual blind spot

  • there are no photoreceptors in the blind spot

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direction of light in the eye

ganglion cells → bipolar cells → rods and cones

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