Journal Club: GABA is (one of) the way the brain communicate with the cochlea

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Today's journal article

  • J.L. Bachman,
  • S.R. Kitcher,
  • L.G. Vattino,
  • H.J. Beaulac,
  • M.G. Chaves,
  • I. Hernandez Rivera,
  • E. Katz,
  • C. Wedemeyer,
    •  
  • & C.J.C. Weisz,
    •  

GABAergic synapses between auditory efferent neurons and type II spiral ganglion afferent neurons in the mouse cochlea

Why I picked this article

This is another publication for the auditory field in PNAS in 2025, and is a very cool paper investigating one of the big mysteries about the auditory system - feedback from the brain to the cochlea. 

Our peripheral auditory system, the cochlea, has four types of innervation that connect the cochlea with the central nervous system. Two are outgoing from the cochlea or "afferent", coming from auditory neurons (spiral ganglion neurons, type I and type II), and two are incoming to the cochlea from the brain or "efferent", called MOC and LOC nerve fibres. Of those, MOC fibres and Type II spiral ganglion neurons make contact with outer hair cells. However, how three of them, outer hair cells, type II spiral ganglion neurons, and MOC influence each other has not been known very much. 

This research uses a highly technical methodology to look at the activity of synapses on outer hair cells. The research focused on GABA, one of the major inhibitory neurotransmitters, and its target "receptor" found in the synapse, to understand the communication between OHC, MOC and type II spiral ganglion neurons. 

Some of the research findings

Animal models:

  • 11-13 day-old animals used for recording from outer hair cells
  • 2-10-day-old animals used for recording from the dendrites of type II spiral ganglion neurons
  • To detect the neurotransmitter of interest, GABA, an optical GABA indicator (iGABASnFR) was artificially introduced into the cochlea (using genetic manipulation) 
  • Activities of target cells/dendrites were measured by patch clamping, a technique that uses a tiny electrode to make an electrical recording from cells. 
  • Important proteins at GABArgic synapses were identified using microscopy. MOC fibers were labelled red by using transgenic mice in which MOC fibers have tdTomoto (red fluorescent label). 

From parts of Fig 4b, Bachman (2025)

The relationship between MOC, type II spiral ganglion neurons and outer hair cells
  • MOC fibres produce and release GABA. 
  • GABA released by MOC fibres seem to regulate MOC itself by changing the neurotransmitter release from MOC. 
  • This is mediated by a receptor called the GABAb-receptor.
  • GABA released by MOC fiber also influence the type II spiral ganglion neurons. 
  • This effect of GABA on type II spiral ganglion neuron synapse is mediated by GABAa-receptors. 

Haruna's takeaway

This is highly technical, very cool research! It's one thing to look at the synapse with beautiful immunohistochemistry, but entirely another and a whole new level of challenge to look at its function in a live cochlear model; to be able to do this is a technical art, and I have full respect for such research expertise. The combination of techniques to use microscopy, functional recording from the cell and imaging to visualise GABA release brings such a nice complement. The kind of three-way communication emerging in this publication is interesting, and I wonder if we can draw on the central nervous system to see if there is anything we can see as analogous. I'm certain there will be more follow-up studies to understand how it works. 

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This is Haruna's 11/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.