The Influence of Dendritic Structure and Function on Binaural Coincidence Detection in the Medial Superior Olive

PROJECT SUMMARY / ABSTRACT The ability to localize sounds in our environment allows us to filter our attention to tasks that deserve it: escaping a predator, capturing our prey, or (selectively) listening to our loved ones speak.

Sound localization in horizontal space is achieved by detecting the difference in time by which sound arrives at each ear, the interaural time difference (ITD).

Humans perceive these ITDs with angular spatial resolution of 1° and time resolution of ten microseconds, the latter being ~3 orders of magnitude faster than the scale at which neurons normally operate. How this is achieved on a subcellular level is not fully understood.

The substrate for ITD processing begins with a dendritic computation deep within the auditory brainstem in an area known as the medial superior olive (MSO).

Within the neural circuitry, excitatory input from each ear onto MSO neurons is exquisitely segregated via the dendritic anatomy: the lateral dendrite and medial dendrite receive input exclusively from the ipsilateral ear or contralateral ear, respectively.

Resulting postsynaptic potentials travel down each dendrite to conjoin at the soma, where their relative temporal synchrony is compared, a process termed binaural coincidence detection.

For optimal coincidence, the external acoustic delay is precisely compensated for by an internal delay, allowing for near simultaneous arrival of binaural inputs at the soma.

This internal delay was traditionally assumed to derive from differences in the physical path lengths of incoming axons (the classic ?Jeffress model?), but alternative models of internal delay have been proposed, most notably one involving glycinergic inhibition.

Despite their critical role as the loci of binaural coincidence detection, largely overlooked is the idea of the dendrites themselves as sources of internal delay.

All models of MSO processing have either omitted dendrites completely or treated them as identical in structure and functional properties.

Because postsynaptic potentials take time to propagate down each dendrite to the soma, that travel time is likely affected by dendritic structure (e.g., path length of travel) as well as the distal dendritic location and spatial spread of each axon?s multiple synapses.

Asymmetries present in either measure could greatly influence the arrival time of postsynaptic input from each ear at the soma.

In support of this idea, our preliminary data demonstrate wide variation in individual neuron structure and sometimes striking asymmetries between the medial and lateral dendritic trees.

I propose that the asymmetry of dendritic structure is an important and unappreciated factor influencing internal delay, affecting each individual neuron?s ITD sensitivity to a differing extent.

To explore this hypothesis, I will use two-photon fluorescence-guided whole-cell recordings of MSO neurons paired with optogenetic stimulation of incoming axons to make direct measurements of dendritic delay and spatial synaptic input patterns even in the finer caliber dendritic processes that have previously been unsampled.

I will construct a morphologically realistic compartmental model using the real morphological and physiological data I collect to simulate the effects that changes in dendritic structure and innervation have on internal delay and ITD sensitivity.