Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron

Abstract

Most neurogenesis in the mammalian brain is completed embryonically, but in certain areas the production of neurons continues throughout postnatal life. The functional properties of mature postnatally generated neurons often match those of their embryonically produced counterparts. However, we show here that in the olfactory bulb (OB), embryonic and postnatal neurogenesis produce functionally distinct subpopulations of dopaminergic (DA) neurons. We define two subclasses of OB DA neuron by the presence or absence of a key subcellular specialisation: the axon initial segment (AIS). Large AIS-positive axon-bearing DA neurons are exclusively produced during early embryonic stages, leaving small anaxonic AIS-negative cells as the only DA subtype generated via adult neurogenesis. These populations are functionally distinct: large DA cells are more excitable, yet display weaker and – for certain long-latency or inhibitory events – more broadly tuned responses to odorant stimuli. Embryonic and postnatal neurogenesis can therefore generate distinct neuronal subclasses, placing important constraints on the functional roles of adult-born neurons in sensory processing.

Spiking and Membrane Properties of Rat Olfactory Bulb Dopamine Neurons

“…we observed a wide distribution of neuronal areas for these DA neurons (Figure 2H), which coincides with previous findings that OB DA neuron subtypes may be distinguished by their size (Pignatelli et al, 2005;Kosaka and Kosaka, 2009;Chand et al, 2015;Pignatelli and Belluzzi, 2017;Galliano et al, 2018;Kosaka et al, 2019). Given the previous findings (Halász et al, 1981;Pignatelli et al, 2005;Kosaka and Kosaka, 2007) of differences in soma sizes between two potential populations of OB DA neurons and our finding that neuronal areas of DA neurons are widely distributed (Figure 2H), we also compared these same properties between recorded DA neurons with different sizes ( Table 2).…”

“…Our membrane properties results indicate that there is no preferred glomerular localization of Large and Small DA neurons. However, a recent study by Galliano et al (2018) found that large TH + /DA neurons were mostly expressed in the deep glomerulus, at the border of GL/EPL. Interestingly, these large neurons exclusively possessed an AIS, indicating that these DA neurons are axonic (Galliano et al, 2018).…”

“…Previous findings commonly categorize OB DA neurons into two size profiles (Halász et al, 1981;Pignatelli et al, 2005;Kosaka and Kosaka, 2007Chand et al, 2015;Pignatelli and Belluzzi, 2017;Galliano et al, 2018;Kosaka et al, 2019). It is possible that OB DA neurons with smaller soma sizes that sometimes lack an axon are PGCs (Pinching and Powell, 1971;Kosaka and Kosaka, 2011;Nagayama et al, 2014), while DA neurons with larger soma sizes and interglomerular projections are SACs (Aungst et al, 2003;Kiyokage et al, 2010;Bywalez et al, 2017).…”

“…A subgroup of potential DAergic PGCs were identified as the "Type-1" PGCs, which express TH (the rate-limiting enzyme present in all DA neurons) and receive excitatory input from the "ON Zone, " corresponding to the area between the middle and the superficial (ONL/GL) border of the glomerulus (Kosaka et al, 1995(Kosaka et al, , 1997(Kosaka et al, , 1998Kosaka, 2005, 2007). A potential DAergic population of SACs provide the most common source of interglomerular projections in the OB (Aungst et al, 2003;Kiyokage et al, 2010), thus, may correspond to the axonic DA neurons, which are mostly found in the deeper (closer to the EPL) portion of the GL (Galliano et al, 2018). Therefore, to distinguish between these two potential types of OB DA neurons, we used whole-cell electrophysiology to investigate differences in the membrane properties of OB DA neurons based on their laminar localization in the GL and size (neuronal area).…”

Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain

“…It has also been shown that dopaminergic OB interneurons born at different times give rise to functionally different cell types: whereas interneurons born postnatally are anaxonic and have no axon initial segment, those born during embryonic development have an axon and an axon initial segment, and are more excitable than postnatally generated cells (Galliano et al, 2018). It is unclear whether this is because of the integration of young neurons into a circuit that differs in maturity, whether the age of the niche affects the differentiation of primary progenitors or whether primary progenitors generate different cell types based on their own age.…”