Weak action potential backpropagation is associated with high‐frequency axonal firing capability in principal neurons of the gerbil medial superior olive

Abstract

Principal neurons of the medial superior olive (MSO) convey azimuthal sound localization cues through modulation of their rate of action potential firing. Previous intracellular studies in vitro have shown that action potentials appear highly attenuated at the soma of MSO neurons, potentially reflecting specialized action potential initiation and/or a physically distant site of generation. To examine this more directly, we made dual patch-clamp recordings from MSO principal neurons in gerbil brainstem slices. Using somatic and dendritic whole-cell recordings, we show that graded action potentials at the soma are highly sensitive to the rate of rise of excitation and undergo strong attenuation in their backpropagation into the dendrites (length constant, 76 μm), particularly during strong dendritic excitation. Using paired somatic whole-cell and axonal loose-patch recordings, we show that action potentials recorded in the axon at distances > 25 μm are all-or-none, and uniform in amplitude even when action potentials appear graded at the soma. This proximal zone corresponded to the start of myelination in the axon, as assessed with immunocytochemical staining for myelin basic protein in single-labelled neurons. Finally, the axon was capable of sustaining remarkably high firing rates, with perfect entrainment occurring at frequencies of up to 1 kHz. Together, our findings show that action potential signalling in MSO principal neurons is highly secure, but shows a restricted invasion of the somatodendritic compartment of the cell. This restriction may be important for minimizing distortions in synaptic integration during the high frequencies of synaptic input encountered in the MSO.

Action Potential Generation in an Anatomically Constrained Model of Medial Superior Olive Axons

“…The resting potential of Ϫ68 mV and the somatic input resistance of 5 M⍀ were set by adjusting the peak conductances of KLT and h current. The somatic surface was set to 8750 m 2 , such that we get a somatodendritic capacitance of 70 pF (Rautenberg et al, 2009), assuming a specific capacitance of 0.8 F/cm 2 (Gentet et al, 2000;Shu et al, 2007). As a consequence, the somatic membrane time constant is 350 s, which closely resembles the measured membrane time constants in vitro (Scott et al, 2005;Couchman et al, 2010).…”

“…The axial resistance results from the geometry of the axonal segment (diameter and length) as well as the specific axial resistivity of 100 ⍀cm, which is in the range of usually assumed values (Mainen et al, 1995;Mainen and Sejnowski, 1996;Shu et al, 2007). The specific model for the sodium channel was taken from Scott et al (2010) with a reversal potential for sodium of 69 mV and a modified conductance density in the axon of 4 nS/ m 2 to fit the firing threshold of our currentclamp measurements (see Fig. 4).…”

“…MSO neurons encode the azimuthal position of low-frequency sounds via differences in the time of arrival at the two ears by their firing rate (Goldberg and Brown, 1969;Yin and Chan, 1990;Fitzpatrick et al, 1997;Brand et al, 2002) with a precision of only a few tens of microseconds. This exquisite temporal precision of binaural coincidence detection is partly achieved by the fast membrane time constants of neurons resulting from the high expression of lowvoltage-activated potassium channels and hyperpolarizationactivated cation channels (Svirskis et al, 2002;Koch et al, 2004;Scott et al, 2005;Mathews et al, 2010;Baumann et al, 2013), both of which are already open at rest. Despite the resulting low input resistance, these neurons can fire at high rates of ϳ100 Hz and more.…”

“…Evidence for this assumption stems predominantly from cortical pyramidal neurons and cerebellar Purkinje neurons using simultaneous somatic and axonal whole-cell recordings (Stuart and Sakmann, 1994;Stuart et al, 1997;Kole et al, 2007;Shu et al, 2007) and voltage-sensitive dye imaging (Palmer and Stuart, 2006;Foust et al, 2010;Palmer et al, 2010;Popovic et al, 2011). At rest, these neurons have relatively high input resistances of 10 -200 M⍀, allowing them to integrate synaptic inputs over several milliseconds.…”

“…These neurons have membrane time constants in the range of only a few hundreds of microseconds and input resistances as low as 5 M⍀ (Scott et al, 2005;Couchman et al, 2010). The MSO is a binaural nucleus in the ascending auditory pathway.…”