Axonal Na⁺ channels detect and transmit levels of input synchrony in local brain circuits

Abstract

<jats:title>Abstract</jats:title><jats:p>Sensory processing requires mechanisms of fast coincidence-detection to discriminate synchronous from asynchronous inputs. Spike-threshold adaptation enables such a discrimination but is ineffective in transmitting this information to the network. We show here that presynaptic axonal sodium channels read and transmit precise levels of input synchrony to the postsynaptic cell by modulating the presynaptic action potential (AP) amplitude. As a consequence, synaptic transmission is facilitated at cortical synapses when the presynaptic spike is produced by synchronous inputs. Using dual soma-axon recordings, imaging, and modeling, we show that this facilitation results from enhanced AP amplitude in the axon due to minimized inactivation of axonal sodium-channels. Quantifying local circuit activity and using network modeling, we found that spikes induced by synchronous inputs produced a larger effect on network activity than spikes induced by asynchronous inputs. Therefore, this input-synchrony dependent facilitation (ISF) may constitute a powerful mechanism regulating spike transmission.</jats:p>

Intrinsic temporal tuning of neurons in the optic tectum is shaped by multisensory experience

“…And yet, with the possible exception of oscillatory networks (Marder and Taylor, 2011;Picton et al, 2018), the exact ways in which intrinsic plasticity contributes to network tuning, remain unclear. We know that neurons adjust their spikiness to match the levels of synaptic activation they experience (Aizenman et al, 2003;Titley et al, 2017), but we also know that intrinsic properties can affect more subtle neuronal tuning to different temporal patterns of activation (Azouz and Gray, 2000;Branco et al, 2010;Fontaine et al, 2014;Jarvis et al, 2018;Ohtsuki and Hansel, 2018;Zbili et al, 2019). This begs the question: do neurons use this type of tuning in practice, dynamically adjusting it to the temporal dynamics of their inputs?…”

“…Circuits in the tectum can learn and reproduce temporal patterns to which they were exposed (Pratt et al, 2008): a property that could in principle be achieved through synaptic changes alone (Lukoševičius and Jaeger, 2009), but which may be easier to achieve through intrinsic temporal tuning (Narayanan and Johnston, 2008;Beatty et al, 2014). Finally, tectal neurons exhibit strong Na channel inactivation, which seems to play a role in collision detection (Jang et al, 2016), can support temporal tuning (Clay et al, 2012;Fontaine et al, 2014;Zbili et al, 2019), and is a known target for plasticity mechanisms (Bianchi et al, 2012).…”

Neural excitability increases with axonal resistance between soma and axon initial segment

“…Whole-cell recordings from L5 pyramidal neurons were obtained as previously described (Boudkkazi et al, 2007 pulse (300-900 pA). As spike threshold is highly sensitive to sodium channel inactivation (Zbili et al, 2020), the latency of the spike was maintained constant (ΔLat<1 ms) before and after axon pinching or axon cut. For this purpose, the amplitude of the current step was adjusted.…”

Large, stable spikes exhibit differential broadening in excitatory and inhibitory neocortical boutons

“…Spikes propagating along the axon trigger neurotransmitter release at presynaptic boutons (Bean, 2007). The amplitude and the duration of the presynaptic spike critically control the gating of voltage-dependent calcium channels (Borst and Sakmann, 1998;Sabatini and Regehr, 1997) and thereby the strength of synaptic transmission (Sakaba and Neher, 2001;Wheeler et al, 1994;Zbili et al, 2020). Therefore, alterations in the shape of the presynaptic action potential contribute to short-and long-term plasticity in the hippocampus (Carta et al, 2014;Geiger and Jonas, 2000).…”