Flipping the Switch: Homeostatic Tuning of Chandelier Synapses Follows Developmental Changes in GABA Polarity

Functional Microstructure of CaV-Mediated Calcium Signaling in the Axon Initial Segment

“…In mature neurons, hyperpolarizing inhibition has been shown to relieve CaV3 channels from steadystate inactivation, thereby promoting rebound spike bursts immediately following an inhibitory epoch (Molineux et al, 2006;Ulrich and Huguenard, 1997). Interestingly, chandelier inputs switch from depolarizing to hyperpolarizing the AIS membrane relatively late in development (Lipkin and Bender, 2020;Pan-Vazquez et al, 2020;Rinetti-Vargas et al, 2017), corresponding to the emergence of synchronized higher-order rhythmicity in cortical networks (Uhlhaas and Singer, 2011). Whether this tight coupling between AIS GABAergic inputs and CaV3s contributes to the development of these network phenomena remains to be explored.…”

Functional microstructure of CaV-mediated calcium signaling in the axon initial segment

“…In mature neurons, hyperpolarizing inhibition has been shown to relieve Ca V 3 channels from steady-state inactivation, thereby promoting rebound spike bursts immediately following an inhibitory epoch (Molineux et al, 2006; Ulrich and Huguenard, 1997). Interestingly, chandelier inputs switch from depolarizing to hyperpolarizing the AIS membrane relatively late in development (Lipkin and Bender, 2020; Pan-Vazquez et al, 2020; Rinetti-Vargas et al, 2017), corresponding to the emergence of synchronized higher-order rhythmicity in cortical networks (Uhlhaas and Singer, 2011). Whether this tight coupling between AIS GABAergic inputs and Ca V 3s contributes to the development of these network phenomena remains to be explored.…”

Chandelier cells shine a light on the formation of GABAergic synapses

“…In fact, the same manipulation in activity in young adults (P40–P46), when GABA at the AIS is inhibitory, resulted in an increase in synapse number [ 21• ]. In short, the polarity of this synapse dictated the direction of its plasticity and suggested that ChCs alter their output to stabilise the activity of pyramidal neurons and circuits [ 52 ]. Although the mechanisms behind this activity-dependent form of plasticity are not yet known, modulation of the levels of expression of any of the molecules described above could play a role.…”