Effects of Dopamine on the Immature Neurons of the Adult Rat Piriform Cortex

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.

Phenotype and Distribution of Immature Neurons in the Human Cerebral Cortex Layer II

“…The presence of dense core vesicles is very interesting and may suggest the presence of synaptic input from monoaminergic axons. In this line, a recent paper from our laboratory has shown that in the piriform cortex of adult rats, immature neurons express dopamine D2 receptors and dopaminergic axons are closely apposed to these cells (Coviello et al, 2020).…”

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

“… 176 Precise mechanisms of induction of these events are not clear yet, however, it was found that enzymatic depletion of PSA promotes the final stages of development of immature neuronal population, 175 the number of cells expressing PSA-NCAM induced by a dopamine receptor agonist decreases due to the differentiation of these cells associated with the loss of PSA-NCAM expression. 177 Then, newly-formed neurons become to be functionally integrated into the pre-existing neuronal ensembles in the cortex. 174 Almost similar mechanism seems to exist in the amygdala where dormant immature DCX+PSA-NCAM+ neurons persist for several years, but then may develop into mature neurons during adolescence.…”

Why Would the Brain Need Dormant Neuronal Precursors?

“…In this context, noradrenaline which controls different aspects of network plasticity involved in olfactory learning (Sullivan and Wilson, 1994;Rangel and Leon, 1995;Harley, 2004;Moreno et al, 2012) might be able to modulate the maturation of dormant precursors (Vadodaria et al, 2017). A role for additional monoamines in dormant precursor maturation has also been suggested (Coviello et al, 2020). Consequently, learning and adaptation in several adult brain regions devoid of neural stem cells might imply the introduction of new neurons arising through awakening of dormant precursors, possibly driven by the processing of salient experiences.…”

“…In this regard, recent research on humans suggested a connection between dormant precursors in the amygdala and autism (Avino et al, 2018;Sorrells et al, 2019). Furthermore, research on animal models implies a relation between dormant precursor maturation and monoamine signaling (Vadodaria et al, 2017;Coviello et al, 2020), opening perspectives toward models of psychosis and/or depression.…”