Developmental alterations and electrophysiological properties

The medial superior olive (MSO) is an auditory brainstem nucleus
within the superior olivary complex. Its functional role for sound
source localization has been thoroughly investigated (for review
see Grothe et al., 2010). However, few quantita tive data about the
morphology of these neuronal coincidence detectors are available
and computational models incorporating detailed reconstructions do
not exist. This leaves open questions about metric characteristics
of the morphology of MSO neurons as well as about
electrophysiological properties that can be discovered using
detailed multicompartmental models: what are the passive parameters
of the membrane? What is the axial resistivity? How do dendrites
integrate synaptic events? Is the medial dendrite symmetric to the
lateral dendrite with respect to integration of synaptic events?
This thesis has two main aspects: on the one hand, I examined the
shape of a MSO neuron by developing and applying various
morphological quantifications. On the other hand, I looked at the
impact of morphology on basic electrophysiological properties and
on characteristics of coincidence detection. As animal model I used
Mongolian gerbils (Meriones unguiculatus) during the late phase of
development between postnatal day 9 (P9) and 37 (P37). This period
of time is of special interest, as it spans from just before
hearing onset at P12 – P13 (Finck et al., 1972; Ryan et al., 1982;
Smith and Kraus, 1987) to adulthood. I used single cell
electroporation, microscopic reconstruction, and
compartmentalization to extract anatomical parameters of MSO
neurons, to quantitatively describe their morphology and
development, and to establish multi-compartmental models. I found
that maturation of the morphology is completed around P27, when the
MSO neurons are morphologically compact and cylinder-like.
Dendritic arbors become less complex between P9 and P21 as the
number of branch points, the total cell length, and the amount of
cell membrane decrease. Dendritic radius increases until P27 and is
likely to be the main source of the increase in cell volume. In
addition, I showed that in more than 85% of all MSO neurons, the
axonal origin is located at the soma. I estimated the axial
resistivity (80 Ω·cm) and the development of the resting
conductance (total conductance during the state of resting
potential) which reaches 3 mS/cm2 in adult gerbils. Applying these
parameters, multi-compartmental models showed that medial versus
lateral dendritic trees do not equally integrate comparable
synaptic inputs. On average, latencies to peak and rise times of
lateral stimulation are longer (12 μs and 5 μs, respectively)
compared to medial stimulation. This is reflected in the fact that
volume, surface area, and total cell length of the lateral
dendritic trees are significantly more larger in comparison to the
medial ones. Simplified models of MSO neurons showed that dendrites
improve coincidence detection (Agmon-Snir et al., 1998; Grau-Serrat
et al., 2003; Dasika et al., 2007). Here, I confirmed these
findings also for multi-compartmental models with biological
realistic morphologies. However, the improvement of coincidence
detection by dendrites decreases during early postnatal
development.