Abstract
The layer II of the adult piriform cortex (PCX) contains a numerous population of immature neurons. Interestingly, in both mice and rats, most, if not all, these cells have an embryonic origin. Moreover, recent studies from our laboratory have shown that they progressively mature into typical excitatory neurons of the PCX layer II. Therefore, the adult PCX is considered a “non-canonical” neurogenic niche. These immature neurons express the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a molecule critical for different neurodevelopmental processes. Dopamine (DA) is a relevant neurotransmitter in the adult CNS, which also plays important roles in neural development and adult plasticity, including the regulation of PSA-NCAM expression. In order to evaluate the hypothetical effects of pharmacological modulation of dopaminergic neurotransmission on the differentiation of immature neurons of the adult PCX, we studied dopamine D2 receptor (D2r) expression in this region and the relationship between dopaminergic fibers and immature neurons (defined by PSA-NCAM expression). In addition, we analyzed the density of immature neurons after chronic treatments with an antagonist and an agonist of D2r: haloperidol and PPHT, respectively. Many dopaminergic fibers were observed in close apposition to PSA-NCAM-expressing neurons, which also coexpressed D2r. Chronic treatment with haloperidol significantly increased the number of PSA-NCAM immunoreactive cells, while PPHT treatment decreased it. These results indicate a prominent role of dopamine, through D2r and PSA-NCAM, on the regulation of the final steps of development of immature neurons in the adult PCX.
Highlights
In the last two decades, many studies have been conducted to characterize a population of immature neurons, which is densely distributed in the layer II of the adult rodent piriform cortex (PCX)
Since tyrosine hydroxylase (TH) can be found in noradrenergic axons, we analyzed the coexpression of TH and dopamine transporter (DAT) in fibers closely apposed to PSA-NCAM immunoreactive neurons, confirming their dopaminergic phenotype (Figures 1B,B1–3)
The present study describes the relationship of dopaminergic neurotransmission with the population of immature neurons in the PCX layer II of adult rats
Summary
In the last two decades, many studies have been conducted to characterize a population of immature neurons, which is densely distributed in the layer II of the adult rodent piriform cortex (PCX). These immature neurons express transcription factors exclusive of excitatory neurons and lack those expressed by interneurons (Gómez-Climent et al, 2008; Bonfanti and Nacher, 2012; Rubio et al, 2016) The function of these immature neurons in the PCX is still a mystery, but some studies have indicated that they are affected by chronic stress and chronic corticosterone treatment (Nacher et al, 2004), as well as by bulbectomy (Gómez-Climent et al, 2011), which are considered animal models of major depression (Planchez et al, 2019). We explored whether the experimental manipulation of dopaminergic signaling via D2r antagonists and agonists may alter the rate of differentiation of the immature neurons in the PCX by quantifying changes in the density of PSA-NCAM-expressing cells in layer II
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