The axonal region most proximal to soma is the axon initial segment (AIS). This region is enriched in voltage-gated sodium channels, which allow to this structure to initiate action potentials. Here, we provide the first identification, and anatomical and functional description of the AIS of substantia nigra dopaminergic neurons.
The experimental data show that the spontaneous firing rate of neurons dependent of size and position of AIS. Thus, neurons with more proximal and larger AIS fire faster than neurons with more distal and smaller AIS. In addition, complementary modeling data indicate that the spontaneous firing rate is reached by a frequency consensus between the activity of the AIS and the somatodendritic compartment. On the other hand, the response of neurons to an aversive stimulus, but not their spontaneous firing rate, is related with the inhibitory synaptic innervation onto the proximal axon-bearing dendrites, which are close to the AIS. Dopaminergic neurons that were inhibited by the aversive stimulus had a higher density of inhibitory synapses onto proximal axon-bearing dendrite than neurons that did not respond.
The findings exposed in the present thesis represent an important progress in the understanding of the morphological and synaptic basis that underlie the spontaneous and driven activity of dopaminergic neurons, which in turn are crucial to maintaining baseline dopamine levels in target areas and neuronal responses to motivationally relevant stimuli.