Conduction Velocity Along the Local Axons of Parvalbumin Interneurons Correlates With the Degree of Axonal Myelination

Abstract

Parvalbumin-containing (PV+) basket cells in mammalian neocortex are fast-spiking interneurons that regulate the activity of local neuronal circuits in multiple ways. Even though PV+ basket cells are locally projecting interneurons, their axons are myelinated. Can this myelination contribute in any significant way to the speed of action potential propagation along such short axons? We used dual whole cell recordings of synaptically connected PV+ interneurons and their postsynaptic target in acutely prepared neocortical slices from adult mice to measure the amplitude and latency of single presynaptic action potential-evoked inhibitory postsynaptic currents. These same neurons were then imaged with immunofluorescent array tomography, the synapses between them identified and a precise map of the connections was generated, with the exact axonal length and extent of myelin coverage. Our results support that myelination of PV+ basket cells significantly increases conduction velocity, and does so to a degree that can be physiologically relevant.

Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition

“…Is myelin required for PV + BC-mediated inhibition? Single PV + BCs typically make 5–15 synapses with a PN in a range of <200 µm, forming highly reliable, fast, and synchronized release sites ( Micheva et al, 2021 ; Packer and Yuste, 2011 ; Tamás et al, 1997 ; Thomson et al, 1996 ). Intercellular variations in both myelin distribution and aberrant myelin patterns have been associated with conduction velocity changes ( Benamer et al, 2020 ; Micheva et al, 2021 ).…”

“…Single PV + BCs typically make 5–15 synapses with a PN in a range of <200 µm, forming highly reliable, fast, and synchronized release sites ( Micheva et al, 2021 ; Packer and Yuste, 2011 ; Tamás et al, 1997 ; Thomson et al, 1996 ). Intercellular variations in both myelin distribution and aberrant myelin patterns have been associated with conduction velocity changes ( Benamer et al, 2020 ; Micheva et al, 2021 ). To examine the role of myelin on inhibitory transmission, we made paired recordings of PV + BCs and L5 PNs with and without myelination, in control or cuprizone-treated PV-Cre; Ai14 mice, respectively ( Figure 3 ).…”

“…The requirement of myelination of PV + BCs to generate gamma rhythms is surprising in view of its sparse distribution in patches of ~25 µm across <5% of the total axon length ( Micheva et al, 2021 ; Micheva et al, 2016 ; Stedehouder et al, 2019 ; Figure 2 , Figure 2—figure supplement 1 ). The sparseness of interneuron myelination previously raised the question whether myelin speeds conduction velocity in these axon types ( Micheva et al, 2016 ; Stedehouder et al, 2019 ; Stedehouder and Kushner, 2017 ).…”

“…Our paired recordings, made near physiological temperature (34–36°C), may have had a limited resolution to detect temporal differences and are not excluding changes in the order of microseconds. To study submillicecond changes, it may be necessary to employ simultaneous somatic and axonal whole-cell recording ( Hu and Jonas, 2014 ) and/or high-resolution anatomical analysis of myelin along the axon path, which recently showed a small albeit positive correlation between percentage of myelination and conduction velocity ( Micheva et al, 2021 ). Furthermore, conduction velocity tuning by myelination of GABAergic axons may become more readily apparent for long-range projections.…”

“…Myelination of axons provides critical support for long-range signaling by reducing the local capacitance that results in rapid saltatory conduction and by maintaining the axonal metabolic integrity ( Cohen et al, 2020 ; Nave and Werner, 2014 ). For PV + BCs, however, the average path length between the axon initial segment (AIS) and release sites involved in local circuit inhibition is typically less than ~200 µm ( Micheva et al, 2021 ; Schmidt et al, 2017 ; Tamás et al, 1997 ), and theoretical and experimental studies indicate the acceleration by myelin may play only a limited role ( Micheva et al, 2021 ; Micheva et al, 2016 ). Another notable long-standing hypothesis is that myelination of PV + axons may be critical for the security and synchronous invasion of presynaptic terminals ( Somogyi et al, 1983 ).…”