Synaptic Input Variability Drives Functional Heterogeneity for Sound Encoding in Globular Bushy Cells

Most neurons in the central nervous system receive convergent input and thereby integrate activity from many other neurons. In sensory pathways, particularly the auditory brainstem, such convergence can enhance sensitivity or sharpen temporal precision when individual inputs are subthreshold and spikes are generated only by multiple coincident inputs (coincidence detection). Within the cochlear nucleus (CN), globular bushy cells (GBCs) receive large axosomatic synapses—the endbulbs of Held—from auditory nerve fibers (ANFs) and transmit their activity to binaural targets with high temporal fidelity. Each GBC is contacted by multiple endbulbs that vary in size, reaching up to a ten-fold difference between the smallest and largest input. To date, it remains unclear how this morphological heterogeneity contributes to function, namely the encoding of sound information. This thesis investigates how variability in the strength of converging endbulb inputs shapes GBCs' output, and how inhibition contributes to auditory encoding. To address this, I performed conductance-clamp recordings in acute brain slices of Mongolian gerbils. Excitatory input patterns were constructed to span anatomically informed ranges of input-strength variation, and inhibitory drive was included to test its regulatory role. Responses were assessed for simple pure-tone and naturalistic amplitude-modulated (AM) sounds. Three consistent results emerged. First, greater variability among excitatory inputs increased overall firing and improved tracking of stimulus envelopes. Second, the same variability reduced spike-timing precision, revealing a trade-off between rate-based envelope coding and faithful temporal coding. Third, inhibition acted primarily as gain control: it decreased sustained spiking and sharpened timing without eliminating reliable onset responses. Together, these findings support a framework in which anatomical heterogeneity positions GBCs along a functional continuum, from precise temporal transfer to improved envelope coding. Inhibitory inputs primarily regulate gain and refine timing, improving onset precision for pure tone and enhancing locking to AM. By combining conductance-clamp recordings with a coincidence-counting cell model (developed in collaboration), this work defines how input-strength variability and inhibition jointly set the timing-rate trade-off in GBCs. The data explain how the operation mode can shift depending on the information provided to the downstream binaural pathways, advancing a mechanistic understanding of the structure-function principles that support robust hearing in natural acoustic environments.