Abstract

In mammalian cerebrum there exist two distinct types of interneurons expressing nitric oxide synthase (NOS). Type I neurons are large in size and exhibit heavy nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemical reaction, while type II cells are small with light NADPH-d reactivity. The time of origin of these cortical neurons relative to corticogenesis remains largely unclear among mammals. Here we explored this issue in guinea pigs using cell birth-dating and double-labeling methods. Bromodeoxyuridine (BrdU) pulse-chasing (2 doses at 50 mg/kg, 12 h apart) was given to time-pregnant mothers, followed by quantification of NADPH-d/BrdU colocalization in the parietal and temporal neocortex in offspring at postnatal day 0 (P0), P30 and P60. Type I neurons were partially colabeled with BrdU at P0, P30 and P60 following pulse-chasing at embryonic day 21 (E21), E28 and E35, varied from 2–11.3% of total population of these neurons for the three time groups. Type II neurons were partially colabeled for BrdU following pulse-chasing at E21, E28, E35 and E42 at P0 (8.6%–16.5% of total population for individual time groups). At P60, type II neurons were found to co-express BrdU (4.8–11.3% of total population for individual time groups) following pulse-chasing at E21, E28, E35, E42, E49, E56 and E60/61. These results indicate that in guinea pigs type I neurons are generated during early corticogenesis, whereas type II cells are produced over a wide prenatal time window persisting until birth. The data also suggest that type II nitrinergic neurons may undergo a period of development/differentiation, for over 1 month, before being NADPH-d reactive.

Highlights

  • Nitric oxide (NO) plays important roles in the nervous system via modulation of neurotransmission, synaptic plasticity and coupling of vasodilatation with neuronal activity (Belvisi et al, 1995; Salemme et al, 1996; Guix et al, 2005; Sunico et al, 2005; Melikian et al, 2009; Toda et al, 2009; Hardingham et al, 2013)

  • We briefly note that the 6 layered basic architecture of the cerebral neocortex as seen in Nissl stain was established in the newborn (Figure 1A), as compared to young adults (Figure 1I)

  • Consistent with an early report (Yan and Garey, 1997a), we observed type I and type II nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) neurons in guinea pig cerebral cortex in the present study, with both types readily present in the newborns (Figures 1B–D)

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Summary

Introduction

Nitric oxide (NO) plays important roles in the nervous system via modulation of neurotransmission, synaptic plasticity and coupling of vasodilatation with neuronal activity (Belvisi et al, 1995; Salemme et al, 1996; Guix et al, 2005; Sunico et al, 2005; Melikian et al, 2009; Toda et al, 2009; Hardingham et al, 2013). Two types of NADPH-d positive neurons, both being interneurons, were proposed based on morphological and neurochemical properties of the cells in nonhuman primate cerebral cortex, with type I neurons being large in size with heavy NADPH-d reactivity, while type II cells small with light histochemical reaction (Yan et al, 1996a). These two types of cells are apparently present in guinea pig, rabbit, cat and human cerebral cortex (Lüth et al, 1994; Yan et al, 1996b; Yan and Garey, 1997a; Estrada and DeFelipe, 1998; Judas et al, 1999; Garbossa et al, 2005; Cruz-Rizzolo et al, 2006; D’Alessio et al, 2007). Type I cells are consistently described in the cerebral cortex in many reports (Bredt et al, 1990; Leigh et al, 1990; Dawson et al, 1991; Vincent and Kimura, 1992; Aoki et al, 1993; Valtschanoff et al, 1993; Rodrigo et al, 1994; Yan et al, 1994; Nogueira-Campos et al, 2012), Frontiers in Neuroanatomy www.frontiersin.org

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