Neurotransmission Flashcards
What is sound?
The displacement of air particles following a sinusoidal pattern of compression and rarefacation….
What is the range of human hearing?
Range of human hearing 20Hz-20KhZ
What are the components of the auditory systems?
Outer Ear- air
Middle Ear- air
Inner Ear- fluid
Central Auditory Pathways
What is the outer ear made up of?
Pinna- cartillagenous structure
Formed from pharyngeal arches 1 & 2 ( 6x Hillocks of His)
Forms between 10th and 18th week in utero Directs soundwaves towards ear canal High pitch > Low pitch
Ear Canal- 1/3 cartilage & 2/3 bone
What is the structure of the tympanic membrane in the outer ear?
Posterior fold
Incus
Umbro
Anulus
Pars tens a
Pars flaccida
Anterior fold
Short process of malleus
Manubrium of malleus
Cone of light
What are the components of the middle ear?
Bones
Malleus, Incus & Stapes
Muscles
Tensor Tympani & Stapedius
Tubes Eustachian Tube
What is the structure of the ossicular chain in the middle ear?
Aditus (inlet) to mastoid antrum
Malleus
Incus
Chorda tympani
Tensor tympani
Tendon of stapedius
Tympanic membrane
Facial nerve In facial canal
Prominence of lateral semicircular canal
Prominence of facial canal
Stapes
Promontory
Tympanic plexus
Tympanic nerve
Lesser pterosaurs nerve
Malleus structure?
Head, neck, anterior surface, manubrium of malleus
Short crus of incus
Body of incus
Lenticular process of incus
Anterior crus
Base of stapes
Posterior crus
Long crus of incus
Head of stapes
What is the size of the malleus?
23mg
8-10mm
What is the size of the stapes?
2.5mg
Smallest bone in the body
Footplate - 1.5 x 2.99mm
What is the role of the middle ear?
Acoustic impedance match between air and fluid- filled inner ear
How many energy is lost transferring from air to fluid?
99.9% loss of energy
How does the middle ear carry out its role?
Amplification of the airborne sound vibration = make it louder
Ratio Area TM : Stapes 14:1
Lever action of ossicles - handle of malleus is 1.3 times longer than long process of incus
Total gain 18.3:1 or 20 - 35 dB
How is energy transferred from outer ear to inner ear?
Air -> fluid
Via Ossicular chain
200 fold increase to boost in pressure form TM to inner ear
What are the roles of muscle in the middle ear?
Protection of the inner ear from acoustic trauma Stiffens the ossciular chain
Stapedius stimulated acoustically
Reflex arc: 3 or 4 neurones
6-7 ms reaction time in cats
25 ms in man - thunderclap, not shotgun
Tensor Tympani-voluntary and involuntary control Chewing !
What is the role of the Eustachian tube?
Ventillation of the middle ear space Drainage of secretions
Often dysfunctional in children – causing hearing loss and middle ear infection
In adults, dysfunction causes shiny things to appear in (some) ENT surgeons homes……
What are the vestibulocohclear apparatus in the inner ear?
A set of fluid filled sacs, encased in bone Cochlear- responsible for hearing Labyrinth- responsible for balance Innervation: Vestibulocochlear nerve
What is the cochlea like?
2.5 turns fluid filled bony tube
2 openings- round window & oval window
3 compartments ( Scala Tympani, Scala Media & Scala Vestibuli) 2 Ionic fluids
What are the cochlear fluids like?
Endolymph - High K+
Perilymph
- Like ECF and CSF
- Na+ rich
Gradients maintained by:
Na, K-ATPase
& NKCC1 CIC-K chlorine channels Ion channel abnormalities- deafness.
What is the structure of the cochlea?
What is the structure of the Eustachian tube?
What are the components of the cochlear?
Basilar membrane
- Narrow at base
- Wide at apex
- Stiff at base
- Floppy at apex
- High frequencies detected at base - - Low frequencies at apex
Like Guitar Strings…
What are the mobile aspects of the ear?
Basilar membrane - mobile
Tectorial membrane - fixed
Movement (compression and rareification)
What is the structure of the organ of corti?
What are the roles of hairs?
Hair cells
Inner Hair Cells- Mechanical transduction
Outer Hair Cells- fine tuning
Base attached to basilar membrane Stereocillia anchored to tectorial membrane.
Shearing forces at the stereocillia
What does displacement of the basilar membrane cause?
Displacement of the basilar membrane causes movement of specialized mechanical transducing cells
What is the structure of the inner hair cells?
Endolymph - stereocilium (K+)
Perilymph - Afferent and efferent - blood? (Depolarize here - Ca 2+)
What happens at the inner hair cells?
Movement of the sterocillia Rapid response required
Mechanically gated K+ channels opened causing depolarization ( K+ rich endolymph)
Depolarization results in opening of voltage gated Calcium channels
Release of neurotransmitter- Glutamate (plus others)
Repolarization through K+ efflux ( into K+ poor perilymph)
What is the relation between tonotopy and the role of the outer hair cell?
Each nerve responds maximally at a specific frequency.
But our ability to discriminate different frequencies is not fully explained by this theory.
Outer Hair Cells can alter the stiffness of the basilar membrane to ensure maximal stimulation at one site and dampened response at another.
Increased resolution
How is sound information encoded?
Sound analysed to encode in formation for neural transmission
FREQUENCY (PITCH) Encoded in nerves by location along the basilar membrane INTENSITY (LOUDNESS) Encoded in nerves by numbers responding and by firing rate SOUND TRANSDUCTION Inner Hair Cells (and OHCs)
AMPLIFICATION Outer Hair Cells
What is the pathway in the ear?
Auditory fibre – spiral ganglion.
Spiral Ganglion to Cochlear nerve ( VIII) Central auditory pathway
What is the central auditory pathway?
Cochlea -> 8th nerve
-> 2. cochlear nucleus
-> 3. superior Oliver’s complex
-> 4. lateral leminiscus
- 5. inferior colliculus
-> medial geniculate body
-> auditory cortex
Numbered - unsure of order - check!!!!
What does the brainstem do?
Sound Localization…
How do we localize sound?
Sound source
Sound wave
Rough estimate of ITD
Left, right ear arrival time
Perceived azimuth in this case
What are interaural time differences?
MSO neurons are coincident detectors responding to only when excitatory signals arrive simultaneously
Anatomically differences in connectivity allow each MSO neuoron to be sensitive to sound source from particular location
- Sound reaches left ear first
- Action potential begins travelling toward MSO
- Sound reach right ear a little later (at right ear)
- Action potential from right ear begins travelling toward MSO (at right ear)
- Action potentials converge on an MSO neuron that responds most strongly of their arrival is coincident (middle)
What is the path of the central auditory pathway?
Eighth Nerve Cochlear Nucleus Olive
Lateral Leminiscus Inferior Colliculus
What is conductive vs sensorineural hearing loss?
Defective outer/middle ear
=CONDUCTIVE HEARING LOSS
Defective Inner Ear
= SENSORINEURAL HEARING LOSS
How do you treat conductiv hearing loss?
Treatment depends on the cause…Improve conduction
Improve amplification - hearing aids
How do you treat sensorineural hearing loss?
Stimulate e.g. auditory brainstem implant - stimulus cochlear nucleus
What are the CNS cell types?
Neurones and glia
Differentiated glia:
- oligodendrocytes
- microglia
- Astrocytes
Others e.g. glial stem cells, oligodendrocytes precursors, ependymal cells
What are neurones?
Specialised for electrical signalling
• Inputs via dendrites
• Action potentials propagate along the axon from the axon hillock
• Mainly formed during development
What can tissue section be stained with?
Tissue sections can be stained with histological stains
• e.g. H&E:
- Haemotoxylin, stains nucleic acids blue
- Eosin – stains proteins red
How do neurones communicate?
Neurons communicate via synapses - 2 types
• Chemical – majority – via neurotransmitters (glutamate, GABA, dopamine, serotonin,
etc.)
• Electrical – less abundant – via direct flow of ions
- enable synchronized electrical activity, e.g. brainstem (breathing) & hypothalamus (hormone secretion)
What occurs in chemical synaptic transmission?
Neurons communicate via synapses - 2 types
• Chemical – majority – via neurotransmitters (glutamate, GABA, dopamine, serotonin,
etc.)
• Electrical – less abundant – via direct flow of ions
- enable synchronized electrical activity, e.g. brainstem (breathing) & hypothalamus (hormone secretion)
What is the structure of an electrical/chemical synapse?
Where are excitatory synapses often concentrated?
On dendritic spines
ER in spines - some proteins are made in spine
What is neural plasticity?
Neural plasticity
- changes in neuronal/synaptic structure and function in response to neural activity - basis of learning and memory
• Spines are dynamic structures – number, size, composition
• Spine remodelling linked to neural activity
• Relevant to disease – e.g. schizophrenia & Alzheimer’s - ↓spine density
What is neuronal heterogeneity?
Neurons differ in their:
• Size
• Morphology
• Neurotransmitter content
• Electrical properties
• E.g. neocortex (right)
What is an example of neuronal heterogeneity that is vulnerable in MND and huntingtons?
Betz cells = upper motor neurons – large, excitatory (glutamatergic,) long projections, pyramidal cells
• Vulnerable in MND
Medium spiny neurons = striatal interneurons – small, inhibitory (GABAergic)
• Vulnerable in Huntington’s disease
What is the aborisation of axons and dendrites?
E.g. cerebellar purkinje cell
What are oligodendrocytes?
Myelinating cells of the CNS
• Unique to vertebrates
• Myelin insulates axon segments, enables rapid nerve conduction
• Myelin sheath segments interrupted by nodes of Ranvier – saltatory conduction
• Provide metabolic support for axons
What is the myelin sheath like?
Formed by wrapping of axons by oligodendrocyte processes (membranes)
• Highly compacted – 70% lipid, 30% protein
• Myelin specific proteins, e.g. myelin basic protein (MBP) can be used as “markers”
What are microglia?
Resident immune cells of the CNS
• Originate from yolk sac progenitors
that migrate into the CNS
• “Resting” state, highly ramified, motile processes survey environment (2-3 μm/min)
• Upon activation (e.g. by ATP), retract processes, become “amoeboid” & motile
• Proliferate at sites of injury - phagocytic
What are the functions of microglia?
Immune surveillance
• Phagocytosis – debris/microbes
• Synaptic plasticity – pruning of spines
• “Bad” (M1) & “good” (M2) microglia
What are astrocytes?
Star-like cells”
• Most numerous glial
cells in the CNS
• Highly heterogeneous – not all star-shaped
• Common “marker” glial fibrillary acidic protein (GFAP)
How do astrocytes contribute to the blood-brain barrier?
Anti-GFAP immunostaining for astrocytes – cell bodies & processes coating capillaries
Dual immunostaining with second astrocyte marker AQP4 reveals more of the vascular network:
GFAP
Aquaporin 4 (water channel – necessary due to the blood- brain barrier – see later)
What are take functions of astrocytes?
Structural - define brain micro-architecture
• Envelope synapses – “tripartite synapse” – buffer K+, glutamate, etc.
• Metabolic support – e.g. Glutamate-Glutamine shuttle
• Neurovascular coupling – changes in cerebral blood flow in response to neural activity
• Proliferate in disease = gliosis or astrocytosis
What are some specialised astrocytes?
Radial glia – important for brain development
Bergmann glia (cerebellum) - green
Muller cells (retina)
What is MND and multiple sclerosis?
Motor neurone disease – adult-onset neurodegenerative disease characterised by loss of upper (motor cortex) and lower (spinal cord) motor neurones
• Multiple sclerosis – autoimmune demyelinating disease where immune cells attack the myelin sheath of oligodendrocytes
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MND spinal cord shows pathological changes in:
A. Motorneurons B. Microglia
C. Astrocytes
D. Alloftheabove
MND symptoms are due to loss of:
A. Motor neurons
B. Microglia
C. Astrocytes
D. All of the above
AcutesymptomsinMSreflectdysfunctionof:
A. Neurons
B. Oligodendrocytes
C. Tlymphocytes
D. Blymphocytes
Pathological CNS lesions in MS involve:
A. Neurons
B. Oligodendrocytes
C. Tlymphocytes
D. Alloftheabove
What are nuclei, tracts, commissures, grey matter and white matter? (CNS terminology)
Abundance of neuronal cell bodies in nuclei
• Axons gathered into tracts
• Tracts that cross midline = commissures
• Grey matter abundant in neural cell bodies & processes – neuropil contains few cell bodies
• White matter contains abundance of myelinated tracts & commissures
What are ganglia, nerves, Schwann cells? (PNS terminology)
Cell bodies & supporting cells located in ganglia – e.g. dorsal root ganglia (DRGs)
• Axons bundled into nerves
• Many PNS axons are enveloped by Schwann cells (myelinating cells
of the PNS – neural crest derived c.f. oligodendrocytes, derived from CNS- resident neural progenitors)
What is the blood brain barrier?
• Dyes injected into blood penetrate most tissues, but not the brain
• Dyes injected into CSF – brain stains → specialised blood-brain barrier
• Formed by endothelial cell tight junctions, basement membrane (few fenestrations), astrocyte end feet & pericytes (contractile, aid blood flow)
• Sensitive to inflammation, hypertension, trauma, ischaemia
• Problem for drug delivery!
Where does CSF drain into?
CSF also drains via perineural routes and via meningeal lymphatics
What are ependymal cells?
Epithelial-like, line ventricles & central canal of spinal cord
• Functions - CSF production, flow & absorption
• Ciliated – facilitates flow
• Allow solute exchange between nervous tissue & CSF
What is the choroid plexus?
Frond-like projections in ventricles
• Formed from modified ependymal cells - villi form around network of capillaries
→ highly vascularised with a large surface area
• Main site CSF production by plasma filtration driven by solute secretion
• Gap junctions between ependymal cells form blood- CSF barrier
What are neurones?
Neurons are highly specialised, heterogeneous cells which are supported by glia
• Patient symptoms typically reflect loss of neuronal function
How are glia important in health and disease?
• Glia are important in health and disease:
- initiation of disease (e.g. multiple sclerosis)
- progression of neurodegenerative diseases (e.g. MND) - research as alternative target for therapy
What are the responses to diff stimuli?
Cognitive analyses - frontal cortex - response suppression
Context - hippocampus and septum - amygdala - conditional emotional responses
Complex neutral stimuli - sensory cortex - amygdala - conditional emotional responses
Neutral stimuli - thalamus - amygdala - conditional emotional responses
Species specific threat stimuli - midbrain and hypothalamus - species specific responses (freeze/flight/fight)
Sudden distal stimuli - hindbrain - startle response
Noxious or contact stimuli - spinal cord - reflexive withdrawal
All stimuli - sensory input - leave as a motor, autonomic and endocrine output