Momentum Programme of the Hungarian Academy of Sciences(Lendület, LP2012-23)
Nemzeti Kutatási és Technológiai Hivatal(OMFB-01678/2009)
Subjects:
Basic medicine
Axo-axonic cells (AACs) in cortical regions selectively innervate the axon initial
segments (AISs) of principal cells (PCs), where the action potentials are generated.
These GABAergic interneurons can alter the activity of PCs, but how the efficacy of
spike control correlates with the number of output synapses remains unclear. Moreover,
the relationship between the spatial distribution of GABAergic synapses and the action
potential initiation site along the AISs is not well defined. Using paired recordings
obtained in the mouse basolateral amygdala, we found that AACs powerfully inhibited
or delayed the timing of PC spiking by 30 ms, if AAC output preceded PC spiking with
no more than 80 ms. By correlating the number of synapses and the probability of spiking,
we revealed that larger numbers of presynaptic AAC boutons giving rise to larger postsynaptic
responses provided more effective inhibition of PC spiking. At least 10-12 AAC synapses,
which could originate from 2-3 AACs on average, were necessary to veto the PC firing
under our recording conditions. Furthermore, we determined that the threshold for
the action potential generation along PC axons is the lowest between 20 and 40 mum
from soma, which axonal segment received the highest density of GABAergic inputs.
Single AACs preferentially innervated this narrow portion of the AIS where action
potentials were generated with the highest likelihood, regardless of the number of
synapses forming a given connection. Our results uncovered a fine organization of
AAC innervation maximizing their inhibitory efficacy by strategically positioning
synapses along the AISs.
