The Potassium Channel Subunit K_vβ1 is Required for Synaptic Facilitation

Abstract

Analysis of the presynaptic action potential’s (APsyn) role in synaptic facilitation in hippocampal pyramidal neurons has been difficult due to size limitations of axons. We overcame these size barriers by combining high resolution optical recordings of membrane potential, exocytosis and Ca2+ in cultured hippocampal neurons. These recordings revealed a critical and selective role for Kv1 channel inactivation in synaptic facilitation of excitatory hippocampal neurons. Presynaptic Kv1 channel inactivation was mediated by the Kvβ1 subunit, and had a surprisingly rapid onset that was readily apparent even in brief physiological stimulation paradigms including paired-pulse stimulation. Genetic depletion of Kvβ1 blocked all broadening of the APsyn during high frequency stimulation and eliminated synaptic facilitation without altering the initial probability of vesicle release. Thus using all quantitative optical measurements of presynaptic physiology, we reveal a critical role for presynaptic Kv channels in synaptic facilitation at small presynaptic terminals of the hippocampal neurons upstream of exocytic machinery.SignificanceNerve terminals generally engage in two opposite and essential forms of synaptic plasticity (facilitation or depression) during high frequency stimulation that play critical roles in learning and memory. Measurements of the electrical impulses (action potentials) underlying these two forms of plasticity has been difficult in small nerve terminals due to their size. In this study we deployed a combination of optical measurements of vesicle fusion and membrane voltage to overcome this previous size barrier. Here, we found a unique molecular composition of Kv1 channel β-subunits that causes broadening of the presynaptic action essential to synaptic facilitation. Disruption of the Kvβ1 inactivation mechanism switches excitatory nerve terminals into a depressive state, without any disruption to initial probability of vesicle fusion.

Synaptotagmin 7 docks synaptic vesicles to support facilitation and Doc2α-triggered asynchronous release

“…This could indicate that facilitation might rely on a post-docking function of syt7. Since the synaptic responses studied here only facilitated slightly (which could be accounted by factors other than calcium sensing, such as action potential broadening; Cho et al, 2020), we restricted the model to the catalytic function of syt7 in synaptic vesicle docking. As in other secretory cell types (Bendahmane et al, 2020), syt7 is indeed able to act as a direct Ca 2+ sensor for exocytosis.…”