Basal forebrain cholinergic neurons have specific characteristics during the perinatal period.

Abstract

Cholinergic neurons of the basal forebrain (BF) represent the main source of cholinergic innervation of large parts of the neocortex and are involved in adults in the modulation of attention, memory, and arousal. During the first postnatal days, they play a crucial role in the development of cortical neurons and cortical cytoarchitecture. However, their characteristics, during this period have not been studied. To understand how they can fulfill this role, we investigated the morphological and electrophysiological maturation of cholinergic neurons of the substantia innominata-nucleus basalis of Meynert complex (SI/NBM) in the perinatal period in mice. We show that cholinergic neurons, whether or not they express γ-aminobutyric acid (GABA) as a co-transmitter, are already functional at embryonic day 18 (E18). Until the end of the first postnatal week, they constitute a single population of neurons with a well-developed dendritic tree, a spontaneous activity including bursting periods, and a short latency response to depolarizations (early-firing). They are excited by both their GABAergic and glutamatergic afferents. During the second postnatal week, a second, less excitable, neuronal population emerges, with a longer delay response to depolarizations (late-firing), together with the hyperpolarizing action of GABAAR-mediated currents. This classification into early-firing (40%) and late-firing (60%) neurons, is again independent of the co-expression of GABAergic markers. These results strongly suggest that during the first postnatal week, the specific properties of developing SI/NBM cholinergic neurons allow them to spontaneously release acetylcholine, or acetylcholine and GABA, into the developing cortex.Significance statement During early postnatal days, basal forebrain cholinergic neurons from the substantia innominata-nucleus basalis of Meynert complex (SI/NBM) play a crucial role in cortical development. However, their morphological and electrophysiological characteristics have not been studied during this period. Here we show that perinatal SI/NBM cholinergic, whether they still/have co-expressed GABAergic markers, belong to a single, homogeneous population of spontaneously active, early-firing, bursting neurons, activated by both glutamatergic and GABAergic afferents until the GABAARs-mediated current polarity shift from excitatory to inhibitory has occurred. This early high excitability suggests that they can release acetylcholine or acetylcholine and GABA into the developing cortical layers and fulfill their well-described role on the early development of cortical neurons and networks.