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Vestibular circuitry and physiology Martha Bagnall, Ph.D. Asst. Professor, Anatomy & Neurobiology [email protected] Today’s plan 1. Lecture 2. Small group problem set solving 3. Discussion of problem set Vestibular sensation: your sixth sense ...doesn’t include interoceptive senses: vestibular, proprioceptive Questions How do vestibular organs sense head movement and orientation? What cellular and circuit properties account for the remarkable speed and linearity of vestibular reflexes? How do other sensory modalities affect central vestibular processing? Vestibular end-organs come in two flavors Otoliths saccule, utricle Vestibular end-organs come in two flavors Semicircular canals superior, posterior, horizontal Otoliths report head translation...and gravity The saccule and utricle contain a gel-like mesh with suspended crystals (otoconia). Both contain hair cells with two dominant orientations. In response to accelerative forces, this gel slides in the corresponding direction, opening some hair cells and closing others. Scarpa’s ganglion contains cell bodies of 8th nerve neurons. Spikes/s Firing of neurons innervating otoliths reports orientation Spikes/s Firing of neurons innervating otoliths reports orientation viewed from back of head Utricle Saccule Semicircular canals report head rotation Canals are filled with fluid (endolymph); at the base, the cupula contains a mass of hair cells all with the same directionality During head rotation, endolymph moves inertially, more slowly than the head itself, causing a deflection of the hair cells in the cupula. The directionality of the hair cells dictates which direction of head movement is excitatory, and which is inhibitory. For horizontal canals, ipsiversive is excitatory, contraversive inhibitory. Firing of neurons innervating canals reports rotation Sinusoidal stimulation J Neurophys 1971 a, b, c Vestibular and auditory afferents are really different Auditory nerves Much lower baseline firing rates Response to sound (pure tones) often involves phase locking: all spikes fired at particular phase of sound oscillation. Dreyer and Delgutte J Neurophys 2006 Crucial differences in end-organ function Semicircular canals Report head rotation Otoliths Report head translation Fluid eventually catches up movement only reported transiently Gel only returns to original position when forces let up; therefore, reports both gravity and translation Have single excitatory direction Have mix of hair cell orientations, not single direction Both are conveyed by nerve fibers with high baseline firing rates Vestibulo-ocular reflex (VOR) Fuchs and Kimm 1975 Vestibulo-ocular reflex (VOR) The VOR and its necessity were described by a physician whose inner ear had been severely damaged by excessive streptomycin therapy. He could read in bed only by bracing his head against the headboard; otherwise the printed page jumped with each heartbeat. When walking he was unable to recognize faces or read signs unless he stood still. https://kin450-neurophysiology.wikispaces.com/VOR VOR is very, very fast Gaze Head Eyes Head Latency from head to eye mvt: 5-6ms Cf saccade or smooth pursuit delay of initiation: 100-200 ms Huterer and Cullen, 2002 Circuit of horizontal angular VOR Push-pull action: excitation from one side and inhibition (and decrease in excitation) from the other Straka and Dieringer 2004 Central vestibular firing in vivo “Vestibular-only” neurons (~40% of population) Fuchs and Kimm 1975 Linear spike generation in vestibular nucleus neurons Recording vestibular nucleus neuron in slice preparation, injecting sinusoidal current du Lac and Lisberger, 1995 Linear spike generation in vestibular nucleus neurons Recording vestibular nucleus neuron, injecting sinusoidal current: linearity of responses both in scale and in additivity Line: Fourier prediction. Dots: data du Lac and Lisberger, 1995 Central vestibular firing in vivo Current injection “Vestibular-only” neurons (~40% of population) Fuchs and Kimm 1975 Keeping neurons firing fast: crucial role of Kv3 Primary dissociated medial vestibular nucleus neurons Slower firing Faster firing (projection (GABAergic) neuron) Injecting action potential waveform during voltage clamp to isolate different currents flowing during a spike Faster-firing neuron has a narrower spike and a 2x larger Kv3 component Gittis et al. 2010, J Neurophys Tail currents: a read-out of open, non-inactivated channels With a long depolarization, Na currents inactivate With brief depolarization, fewer Na channels inactivate. Tail current (arrow) is measure of channels that were open (ie not inactivated) when the cell was repolarized. Keeping neurons firing fast: crucial role of Kv3 Primary dissociated medial vestibular nucleus neurons Slower firing Faster firing (projection (GABAergic) neuron) Injecting action potential waveform during voltage clamp to isolate different currents flowing during a spike Faster-firing neuron has a narrower spike and a 2x larger Kv3 component Artificially broadening the spike, mimicking TEA application to block Kv3, yields diminished Na current on subsequent spike. Tail current Gittis et al. 2010, J Neurophys Linear synaptic processing from vestibular afferents Stimulating vestibular nerve afferents at varying instantaneous rate (top). Ignoring first few pulses, which show system adapting out of quiescence, EPSC amplitude is invariant. Synaptic stim of vestibular nerve also produces linear changes in postsynaptic FR Bagnall et al, 2008 Linear synaptic processing is unusual! Hippocampal CA3 CA1 synapse Klyachko and Stevens 06 Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks....Virtually all types of synapses are regulated by a variety of short-lived and long-lasting processes, some of which lead to a decrease in synaptic strength and others that lead to synaptic enhancement. Zucker and Regehr 02 Linear synaptic processing is unusual! Abbott et al Science 97 Cortical synapse: exponential decay of EPSC amplitude with respect to rate, yielding a “normalization” function: total charge transfer (B, dashed line) quickly maxes out. Vestibular synaptic linearity indicates that synapses don’t HAVE to be nonlinear—instead, that’s a typical function that may be “valued” by a given circuit. Here, the demands of behavior are towards linearity. Changing the input/output relationship (gain) Blockade of BK channels with iberiotoxin increased gain Step currents in slice preparation to measure cellular gain Bidirectional changes in gain with ambient [Ca] Smith et al 2002 Central vestibular processing in vivo Cerebellum Thalamus, hippocampus, oculomotor Vestibular nuclei (brainstem) Abducens Vestibular nuclei (brainstem) Abducens Spinal cord Vestibular afferents (canals and otoliths) Central vestibular firing in vivo “Position-vestibular-pause” neurons (~50% of population): carrying both vestibular and eye movement info Fuchs and Kimm 1975 Central vestibular processing Cerebellum Thalamus, hippocampus, oculomotor Vestibular nuclei (brainstem) Vestibular nuclei (brainstem) Vestibular afferents (canals and otoliths) Eye position info Abducens Abducens Spinal cord Passive and active head movement encoding Cullen 2011 Passive and active head movement encoding Cullen 2011 Central vestibular processing: it’s complicated Cerebellum Thalamus, hippocampus, oculomotor Vestibular nuclei (brainstem) Vestibular nuclei (brainstem) Vestibular afferents (canals and otoliths) Eye position info Abducens Proprioceptive neck/ body or movement planning info Abducens Spinal cord Summary Two types of vestibular end-organs have different encoding properties Vestibular circuits are also responsible for distinguishing between intentional and unintentional head movement Unusual linearity of cellular and synaptic properties in the vestibular nucleus may be related to the unusual linearity of vestibular reflexes Vestibulo-ocular reflex is stunningly rapid and highly accurate; relies on high firing rates at baseline and distinctive forms of cellular and synaptic plasticity to maintain throughout life Vestibular sensation also influences many other systems: spinal reflexes, heart rate, blood pressure, etc