Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, SA001

Research Symposium

A developmental switch in the activity-dependent plasticity of axo-axonic synapses along the axon initial segment

J. Burrone1,2

1. Centre for Developmental Neurobiology, King's College London, London, United Kingdom. 2. MRC Centre for Neurodevelopmental Disorders, King's College London, London, United Kingdom.

The axon initial segment (AIS) is an axonal structure close to the soma with a high density of sodium and potassium channels that defines the site of action potential generation. In principal cells of the cortex, it is also innervated by inhibitory synapses formed by a specific type of GABAergic interneuron, the Chandelier cell. Previous work in the lab has focused on activity-dependent forms of plasticity of the AIS and its synapses (Grubb and Burrone, 2010; Wefelmeyer et al., 2015). Here, we present data characterising the changes these structures undergo during postnatal development in the rodent neocortex and the role that local cortical activity plays in this process. We used a recently developed inducible Cre mouse line, Nkx2.1-CreER, to label Chandelier cell interneurons (Taniguchi et al., 2013). By visualising Chandelier cell axons and their synaptic boutons in the somatosensory cortex in vivo, as well as in fixed brain preparations, during development, we uncovered a narrow temporal window of synapse formation at the AIS (from P14-P16). We then manipulated the activity levels of either pyramidal neurons or individual Chandelier cells during this period of synapse formation (P12-P18), using a chemogenetic approach. We found that increases in the activity of cortical networks results in a reversible decrease in the length of the AIS as well as the number of axo-axonic synapses it received. Increasing activity specifically in Chandelier cells mirrors the synaptic effect, suggesting this plasticity is cell autonomous. However, when network activity was increased in adult animals (P40-P46) we saw the opposite effect: an increase in axo-axonic synapses along the AIS. This puzzling switch in the direction of axo-axonic synapse plasticity can be explained in the context of homeostatic plasticity. To explore this, we used a genetically-encoded voltage indicator expressed in pyramidal cells to show that ChCs transition from being excitatory at P12-P18, to inhibitory at P40-P46, in agreement with previous findings (Rinetti-Vargas et al., 2017). We propose that this switch in synapse polarity during development is paralleled by a switch in the direction of axo-axonic synapse plasticity that acts to stabilise network activity.

Where applicable, experiments conform with Society ethical requirements