isolating-culturing-vestibular-spiral-ganglion-somata-from-neonatal

Isolating and Culturing Vestibular and Spiral Ganglion Somata from Neonatal Rodents for Patch-Clamp Recordings

The compact morphology of isolated and cultured inner ear ganglion neurons allows for detailed characterizations of the ion channels and neurotransmitter ...

University of Southern California

Vestibular ganglion neurons (VGNs) transmit information along parallel neuronal pathways whose signature distinction is variability in spike-timing; some fire at regular intervals while others fire at irregular intervals. The mechanisms driving timing differences are not fully understood but two opposing (but not mutually exclusive) hypotheses have emerged. In the first, regular-spiking is inversely correlated to the density of low-voltage-gated potassium currents (). In the second, regular spiking is directly correlated to the density of hyperpolarization-activated cyclic nucleotide-sensitive currents (). Supporting the idea that variations in ion channel composition shape spike-timing, VGNs from the first postnatal week respond to synaptic-noise-like current injections with irregular-firing patterns if they have  and with more regular firing patterns if they do not. However,  firing patterns are not as regular as those  Here we considered whether highly-regular spiking requires  currents and whether this dependence emerges later in development after channel expression matures. We recorded from rat VGN somata of either sex aged postnatal day (P)9-P21. Counter to expectation,  firing patterns were less diverse, more transient-spiking, and more irregular at older ages than at younger ages. Resting potentials hyperpolarized and resting conductance increased, consistent with developmental upregulation of  Activation of  (by increasing intracellular cAMP) increased spike rates but not spike-timing regularity. In a model, we found that activating  counter-intuitively suppressed regularity by recruiting  Developmental upregulation in  appears to overwhelm  These results counter previous hypotheses about how  shapes vestibular afferent responses. Vestibular sensory information is conveyed on parallel neuronal pathways with irregularly-firing neurons encoding information using a temporal code and regularly-firing neurons using a rate code. This is a striking example of spike-timing statistics influencing information coding. Previous studies from immature vestibular ganglion neurons (VGNs) identified hyperpolarization-activated mixed cationic currents () as driving highly-regular spiking and proposed that this influence grows with the current during maturation. We found that  becomes less influential, likely because maturing VGNs also acquire low-voltage-gated potassium currents (), whose inhibitory influence opposes  Because efferent activity can partly close , VGN firing patterns may become more receptive to extrinsic control. Spike-timing regularity likely relies on dynamic ion channel properties and complementary specializations in synaptic connectivity.

Christopher Ventura

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