NEUROBIOLOGY B2

• Inner ear


  • Bony structure comprised of cochlea (audition) and the semicircular canals of the vestibular system (balance)

  
• Cochlea


  Bony tube containing fluid in chambers separated by a thin membrane
• Fluid movement in the cochlea

  1. Sound pressure waves entering the ear sets up vibrations of the tympanic membrane (ear drum)

  2. Vibration of the stapes applies pressure to the fluid in the upper chamber (scala vestibuli)

  3. Fluid moves along the scala vestibuli and around the apex of the cochlea (helicotrema)

  4. Fluid pressure is then 'relived' by movement on an additional membrane at the round window -- this bulges successively outwards and inwards as the stapes moves in response to vibration of the tympanic membrane

  
• Basilar membrane


  • 5 times broader at apex (also thicker and less rigid)
  • High frequencies set up more vibration of the end closest to the oval and round windows
  • Lower frequencies set up vibration at the distant end
  • Location on the basilar membrane corresponds to sound tone or pitch (=frequency)
  • The basilar membrane is said to be tonotopic in its organisation

  
• Organ of Corti


  • Two rows of hair cells (inner and outer)
  • Inner hair cells are the main receptors responsible for our perception of sound
  • Both rows have their tips embedded into a tectorial/gelatinous membrane that protrudes into a special fluid chamber --> attached to the 'inner' side only
  • The fluid in the scala media is very high in potassium (very high [K+] - unusual)
  • Vibration of basilar membrane sets up 'shearing' motion tips of the hair cells, which are deflected back and forth as their tips adhere to the tectorial membrane

  
• Inner hair cells


  • ~4000 inner hair cells at birth: need to last lifetime
  • Specialised mechanoreceptors
  • Longer and 'floppier' at the distant end of the cochlea: aid tuning to lower frequencies (enhances tonotopic map)
  • Experiments where hair cells are 'pushed' with an artificial probe show that voltage change across the cell membrane is proportional to force encode amplitude and phase in their graded receptor potential
• Hair cells and cation channels

  • Vibration of basilar membrane results in opening of cation channels in the hair cells stereocilia
  • Very fine structures (3nm 'tip links') connect the tips of the stereocilia to one another
  • Spring-like tip-links are believed to directly gate around 100 cation channels
  • K+ produces an inward current as channels open along with Ca2+

  
• Stimulus strength required to elicit a 1mV response in hair cells is lower at the distant end of the basilar membrane

  
• Functional role of outer hair cells


  Believed to 'sharpen' frequency tuning of inner hair cells

  
• There is a logarithmic relationship between the magnitude of sound and the perceived loudness (10 times the sound pressure for each increment in perception)
• Outer hair cells


  Generate sound in the inner ear via mechanical movements ('oto-acoustic emissions')

  
• Responses of hair cells

  • Mechanical gating of ion channels is fast
  • Recordings from hair cells show that they respond to sounds with 'in phase' graded response
  • Refractory period of spikes would be very limiting
  • Response timing and neurotransmitter release precise to a few microseconds
  • Neurotransmitter is released onto spiral ganglion neurons which then transmit with action potentials
  • A rate code could not be used by the receptors without losing resolution of timing (phase)
  • Behavioural analysis of human ability to localise sounds suggests that our ears encode phase with a resolution of 10us or better

  
• Phase-locked firing


  • Hair cells release neurotransmitter precisely in phase with stimulus
  • Auditory interneurons' action potentials cannot fire on every cycle of sound at high frequencies (>200Hz)
  • Worse at lower amplitude (quieter) sound waves (less spike intensity)
  • When spikes are generated, they occur precisely in phase with the depolarisation of the hair cells: accurate to within 10us
• Auditory interneurons of the spiral ganglia

  • 10-15 afferent interneurons per inner hair cell - multiple to ensure an AP is fired at every cycle of sound
  • Convert graded signal into a spike code for transmission to higher centres for sound processing
  • Individuals neurons do use a rate code to signal loudness, but with limited dynamic range
  • Dynamic range improved by different neurons having different thresholds for spike generation
  • Auditory neurons of spinal ganglia exhibit phase-locked firing

  
• Spiral ganglion neurons


  • Project to the cochlear nuclei in the brain stem (in medulla) where they synapse with several other pathways
  • Main projection to the auditory cortex is an ascending pathway via 'relay' nuclei in the mid-brain: inferior colliculus (IC) and medial geniculate nucleus (MGN)
  • Cortex projection involved in complex 'pattern recognition' (e.g. speech)
  • Inferior colliculus contains neurons that respond only to specific sound locations
  • Since no map of space exists in the cochlea, inferior colliculus neurons must somehow compute location

  
• Phase preservation pathway and spatial localisation

  • Because neurotransmitter release triggers action potentials in phase with hair cell movement in multiple second order neurons (spiral ganglion cells) action potentials can be triggered even when come neurons are refractory
  • This is important as it means that the population of ganglion cells is able to present phase information in the timing of their spikes
  • Brain stem nuclei to which the spiral ganglion neurons project are then able to compare sounds coming from two ears to determine the location of sounds in space (due to the delay in sound reaching the more distant ear when sounds are to one side) --> SPATIAL LOCALISATION
  • Whilst there is not spatial map in the ear, the brain is able to compute one

  
• There is high potassium in the endolymph
• The stapes transmits the vibrations to the oval window
• The basilar membrane vibrates due to the pressure difference between the scala vestibuli and tympanum
• The round window allows fluid to move freely
• The basilar membrane moves up and down due to the pressure changes caused by the vibrating fluid
• The basilar membrane has a peak frequency response at its point of maximum displacement
• The basilar membrane has a peak frequency response at its base
• The cochlear duct is filled with perilymph
• The basilar membrane has a low frequency response at its tip
• Inner hair cells have afferent fibres attached to them
• The organ of Corti has sensory epithelium containing inner and outer hair cells
• Hair cells are located on the organ of Corti, which sits on top of the basilar membrane
• Stereocilia have mechanically gated ion channels that open when bent
• The cochlea is divided into three compartments, including the scala vestibuli, scala media, and scala tympani.
• The scala vestibuli contains perilymph, which is similar to extracellular fluid found elsewhere in the body.
• The scala media contains endolymph, which is different from perilymph and has high potassium levels.
• Afferent fibers are connected to inner hair cells via synapses
• Efferent fibers are connected to outer hair cells via synapses
• Outer hair cells are responsible for amplification
• The scala tympani is continuous with the middle ear cavity and contains perilymph.