Sodium Along With Low-Threshold Potassium Currents Enhance Coincidence Detection of Subthreshold Noisy Signals in MSO Neurons

Abstract

Voltage-dependent membrane conductances support specific neurophysiological properties. To investigate the mechanisms of coincidence detection, we activated gerbil medial superior olivary (MSO) neurons with dynamic current-clamp stimuli in vitro. Spike-triggered reverse-correlation analysis for injected current was used to evaluate the integration of subthreshold noisy signals. Consistent with previous reports, the partial blockade of low-threshold potassium channels (I(KLT)) reduced coincidence detection by slowing the rise of current needed on average to evoke a spike. However, two factors point toward the involvement of a second mechanism. First, the reverse correlation currents revealed that spike generation was associated with a preceding hyperpolarization. Second, rebound action potentials are 45% larger compared to depolarization-evoked spikes in the presence of an I(KLT) antagonist. These observations suggest that the sodium current (I(Na)) was substantially inactivated at rest. To test this idea, I(Na) was enhanced by increasing extracellular sodium concentration. This manipulation reduced coincidence detection, as reflected by slower spike-triggering current, and diminished the hyperpolarization phase in the reverse-correlation currents. As expected, a small outward bias current decreased the pre-spike hyperpolarization phase, and TTX blockade of I(Na) nearly eliminated the hyperpolarization phase in the reverse correlation current. A computer model including Hodgkin-Huxley type conductances for spike generation and for I(KLT) showed reduction in coincidence detection when I(KLT) was reduced or when I(Na) was increased. We hypothesize that desirable synaptic signals first remove some inactivation of I(Na) and reduce activation of I(KLT) to create a brief temporal window for coincidence detection of subthreshold noisy signals.

Posthearing Developmental Refinement of Temporal Processing in Principal Neurons of the Medial Superior Olive

“…Previous studies of the MSO have highlighted the importance of voltage-gated potassium currents, particularly those active at low voltages, in shaping action potential signaling. For example, reducing I K(LVA) in MSO principal neurons from P12-P14 gerbils with blockers of Kv1 subunits, DTX-K and dendrotoxin-I, lowered the current threshold for action potential initiation and caused repetitive firing (Svirskis et al, 2002(Svirskis et al, , 2004. Similar effects were found in older animals with a less-specific blocker, 1 mM 4-aminopyridine (Smith, 1995).…”

“…Although the mechanism for extracting ITDs from these excitatory and inhibitory inputs has yet to be fully elucidated (for review, see Joris et al, 1988;Grothe, 2003;Palmer, 2004), ITD information is conveyed to higher auditory centers through a rate code (Goldberg and Brown, 1969;Yin and Chan, 1990;Spitzer and Semple, 1995;Brand et al, 2002). To detect these rapid time-varying cues, time-coding auditory neurons in the MSO and elsewhere in the brainstem exhibit biophysical specializations, such as low voltage-activated potassium currents (I K(LVA) ), which allow them to signal with high temporal fidelity (Svirskis et al, 2004) (for review, see Trussell, 1999).…”

Computation of Interaural Time Difference in the Owl's Coincidence Detector Neurons

“…The major difference between our in vivo observation and the in vitro observations are the frequency range that NL cells cover, and the existence of spontaneous inputs. No matter how many low-voltage activated potassium channels (KLVA), long been supposed to be a key for phasic firing (Manis and Marx, 1991;Svirskis et al, 2004), were incorporated, the model cells generated multiple spikes to current injection as nodal Na channels were increased (Ashida et al, 2007). Also, even in models with phasic firing, adding noise or high-frequency components sometimes induces multiple spikes (Higgs et al, 2006).…”

Modeling Binaural Responses in the Auditory Brainstem to Electric Stimulation of the Auditory Nerve

“…Low-threshold potassium (KLT) channels are widely expressed in auditory neurons specialized for rapid temporal processing, including neurons in the MSO, where neural sensitivity to ITD first arises (Eatock 2003;Svirskis et al 2004;Scott et al 2005;Johnston et al 2010;Mathews et al 2010). KLT currents enable neurons to accurately encode temporal information at high frequencies (Manis and Marx 1991;Trussell 1997Trussell , 1999Rothman and Manis 2003a).…”