Large, Stable Spikes Exhibit Differential Broadening in Excitatory and Inhibitory Neocortical Boutons

Small size of recorded neuronal structures confines the accuracy in direct axonal voltage measurements

“…In addition to providing a useful tool for predicting and correcting instrumental distortions our simulations confirmed that complete elimination of the instrumental disturbance was not possible during recordings (Ritzau-Jost et al, 2021), since substantial difference persists between the measured and native APs, even when the capacitance compensation reached the maximally attainable level (see Figure 5C ). The model raised the possibility that inadequate local signal generation also significantly contribute to the alterations in AP shapes in addition to filtering that affects recordings through patch pipettes.…”

“…As previously described for small, electrotonically compact neurons (D’Angelo, De Filippi, Rossi, & Taglietti, 1995; Goodman, Hall, Avery, & Lockery, 1998; Rohrbough & Broadie, 2002), we found that even with careful capacitance neutralization, the capacitive load added by the recording instrument substantially altered the intrinsic electrical behavior of the axon ( Figures 4 and 5 ). Using a simplified neuronal representation, we confirmed with that instrumental capacitance effectively attenuates the action potentials in small neuronal structures ( Figure 7 ) emphasizing again that C pip reduction can substantially improve the accuracy of the measured voltage signal (Dudel, Hallermann, & Heckmann, 2000; Levis & Rae, 1993; Ogden & Stanfield, 1994; Ritzau-Jost et al, 2021; Sakmann & Neher, 1983). Interestingly, we have shown that increase in the R access reduced the instrumental impact on the cellular electrogenesis (probably due to effective electrical isolation of the neuronal structure from the recording pipette) suggesting that high impedance recording can have also advantages when experimental subject is small.…”

“…The simple Hodgkin-Huxley type conductance models with six free parameters were sufficient to restore the experimentally recorded MF AP waveforms. Although APs in the distal MFs can be described with a similar standard Hodgkin-Huxley type gating (Engel & Jonas, 2005; Ohura & Kamiya, 2018), AP simulation in other neuron types or in other subcellular elements required more detailed kinetic schemes (Stefan Hallermann et al, 2012; Ritzau-Jost et al, 2014; Ritzau-Jost et al, 2021; Schmidt-Hieber & Bischofberger, 2010). Therefore, implementation of more elaborated conductance models and inclusion of additional conductances can further improve our simulations and adapt to multiple activity regimes, such as the plasticity of AP shapes during sustained activity (Geiger & Jonas, 2000).…”

“…Therefore, accurate AP measurements are essential to understand fundamental mechanisms of the neuronal information flow. Recent developments of the recording apparatus allows collecting voltage signals from the finest axonal structures (Kawaguchi & Sakaba, 2015; Novak et al, 2013; Ritzau-Jost et al, 2021; Rowan, DelCanto, Jianqing, Kamasawa, & Christie, 2016; Vivekananda et al, 2017). However, the interpretation of these signals are still limited because signal distortions caused by the recording pipette and amplifier circuits remains elusive (Ritzau-Jost et al, 2021).…”

“…Recent developments of the recording apparatus allows collecting voltage signals from the finest axonal structures (Kawaguchi & Sakaba, 2015; Novak et al, 2013; Ritzau-Jost et al, 2021; Rowan, DelCanto, Jianqing, Kamasawa, & Christie, 2016; Vivekananda et al, 2017). However, the interpretation of these signals are still limited because signal distortions caused by the recording pipette and amplifier circuits remains elusive (Ritzau-Jost et al, 2021). We reasoned that as computational modeling allows the precise reconstruction of the native electrical behavior of the most complex neuronal structures (Henrik Alle, Roth, & Geiger, 2009; Beaulieu-Laroche & Harnett, 2018; Branco & Häusser, 2011; Jayant et al, 2017; Kwon, Sakamoto, Peterka, & Yuste, 2017) it should be similarly possible to simulate the behavior of the recording instruments.…”