Journal Club: Following auditory neurons (SGN type Ia and Ic) to the brain stem

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Today's journal article

Wong NF, Brongo SE, Forero EA, Sun S, Cook CJ, Lauer AM, Müller U, Xu-Friedman MA. Convergence of Type 1 Spiral Ganglion Neuron Subtypes onto Principal Neurons of the Anteroventral Cochlear Nucleus. 

Why I picked this article

This publication explores the connection from auditory neurons to the brainstem! 

Our sense of hearing is carried by auditory neurons, or spiral ganglion neurons. The cell bodies of spiral ganglion neurons are located inside our hearing organ, the cochlea, and the two extensions from spiral ganglion neurons receive signals from auditory sensory cells on one side, and propagate signals on the other side, all the way to the "cochlear nucleus" of the brain. Different subtypes of spiral ganglion neurons carry information to different cell types/locations in the brainstem to allow complex auditory signalling, but we don't yet fully understand how they work. 

To add more knowledge to this topic, this research focuses on type Ia and Ic subgroups of spiral ganglion neurons and investigates how they carry information to the brainstem.

Some of the research findings

Animal model:

  • Multiple transgenic mice were mated to generate transgenic mice where a subpopulation of spiral ganglion neurons can be visualised by fluorescent protein. Original mice groups were: 
    • CBA/CaJ mice background (The Jackson Laboratory RRID:IMSR_JAX:000654)
    • ChR mice (with yellow fluorescent marker = a floxed channelrhodopsin-eYFP construct)
    • CALB2-Cre mice (CreERT2 in CALB2 locus. Calb2 has been found in type Ia spiral ganglion neurons. )
    • LYPD1-Cre mice (CreERT2 in LYPD-1 locus. LYPD-1 has been found in type Ic spiral ganglion neurons.)
  • By crossing CALB2-Cre mice with ChR mice, fluorescent protein labels type Ia spiral ganglion neurons. 
  • By crossing LYPD1-Cre mice with ChR mice, fluorescent protein labels type Ic spiral ganglion neurons. 
  • Researchers confirmed that the fluorescent protein expression in these mice appeared as expected, with normal hearing. 
  • Brain slices were prepared to use electrophysiology to characterise auditory neurons. 

Wang NF et al. (2025), Figure Di&Fi
Findings: Responses triggered by CALB2-spiral ganglion neurons vs LYPD1-spiral ganglion neurons
  • Recordings were made from "bushy cells", specialised neuron in the anterior ventral cochlear nucleus. Synapses formed by the fluorescently visualised spiral ganglion neurons were targeted.
  • Overall, electrophysiological characteristics, CALB2 and LYPD1-subgroups of spiral ganglion neurons did not differ very much. This included:
    • the characteristic of bushy cell activation, as measured by excitatory post-synaptic potential.
    • the contribution from specific receptors at the synapses (NMDA:AMPA) 
    • the size of a unit of neurotransmitter release
    • the plasticity (=adaptability) of the synapse.
  • Comparison of neurons receiving synapses from CALB2-subgroup of spiral ganglion neurons and neurons receiving synapses from LYPD1-subgroup did not show a difference in the spontaneous rate of threshold. 
The findings from this study suggest that the diverse characteristics observed among subgroups of spiral ganglion neurons (type Ia, Ib, Ic) are not observed once signals reach bushy cells in the brainstem. The authors suggest that at the brainstem level, there is "convergence" where cells receive input from multiple subgroups of spiral ganglion neurons, rather than continuing to keep them as separate signal pathways. 

Haruna's takeaway

This is a very nice approach to use multiple combinations of transgenic mice to enable visualisation of a subgroup of spiral ganglion neurons specifically. I am envious, as this is not a type of study that can be done in New Zealand, because of the extremely high cost of maintaining a single line of transgenic mouse colonies relative to larger countries. 

It is very interesting that at the bushy cell level, there is minimal "subtype difference", despite the fact that spiral ganglion neurons were so diverse. So, how does the intensity information coming from spiral ganglion neurons get maintained and processed? Maybe things are even more complicated than we imagined.... isn't it always the case! 

The authors mention in the discussion the possibility that the observed characteristic may be because mice have poorer spatial acuity of sound, and therefore, perhaps sound intensity information (like a subtle difference between the intensity of sound coming from right and left, which is important for spatial acuity). Authors hence finish by saying it will be valuable to examine if how their observation may translate to other species with more specialised directional hearing. 

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This is Haruna's 15/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.