Coordinated postnatal maturation of striatal cholinergic interneurons and dopamine release dynamics in mice.

Dynamic changes in motor abilities and motivated behaviors occur during the juvenile and adolescent periods. The striatum is a subcortical nucleus critical for action selection, motor learning and reward processing. Its tonically active cholinergic interneuron (ChI) is an integral regulator of the synaptic activity of other striatal neurons, as well as afferent axonal projections of midbrain dopamine neurons. Thalamic and dopaminergic inputs initiate pauses in ChI firing following salient sensory cues that are extended for several hundred milliseconds by intrinsic regenerative currents. Here, we characterize the electrophysiological and morphological features of ChIs during mouse postnatal development. We demonstrate that ChI spontaneous activity increases with age while the duration of the pause in firing induced by depolarizing inputs decreases during postnatal development. Maturation of ChI activity is driven by two distinct physiological changes: decreased amplitude of the afterhypolarization between P14 and P18 and and increased Ih conductance between the late postnatal period and adulthood. Finally, we uncover postnatal changes in dopamine release properties that are mediated by cholinergic signalling. At P10, striatal dopamine release is diminished compared to the adult, but our data show efficient summation of dopamine relase evoked by multiple grouped stimuli that subsides by P28. Blockade of nictonic acetylcholine receptors enhances release summation in mice older than P28 but has little effect at P10. These data demonstrate a physiological maturation of ChI activity and indicate a reciprocal interaction between the postnatal maturation of striatal ChI and dopamine neurotransmission.