Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

Abstract

Understanding the development of cortical interneuron phenotypic diversity is critical because interneuron dysfunction has been implicated in several neurodevelopmental disorders. Here, tyrosine hydroxylase (TH)-immunoreactive neurons in the developing and adult rat cortex were characterized in light of findings regarding interneuron neurochemistry and development. Cortical THimmunoreactive neurons were first observed two weeks postnatally and peaked in number three weeks after birth. At subsequent ages, the number of these cell profiles was gradually reduced, and they were seen less frequently in adults. No DNA fragmentation or active caspase 3 was observed in cortical TH cells at any age examined, eliminating cell death as an explanation for the decrease in cell number. Although cortical TH cells reportedly fail to produce subsequent catecholaminergic enzymes, we found that the majority of these cells at all ages contained phosphorylated TH, suggesting that the enzyme may be active and producing L-DOPA as an end-product. Morphological criteria and colocalization of some TH cells with glutamic acid decarboxylase suggests that these cells are interneurons. Previously, parvalbumin, somatostatin, and calretinin were demonstrated in nonoverlapping subsets of interneurons. Cortical TH neurons colocalized with calretinin but not with parvalbumin or somatostatin. These findings suggest that the transitory increase in TH cell number is not due to cell death but possibly due to alterations in the amount of detectable TH present in these cells, and that at least some cortical TH-producing interneurons belong to the calretinin-containing subset of interneurons that originate developmentally in the caudal ganglionic eminence.

Tyrosine hydroxylase-producing neurons in the human cerebral cortex do not colocalize with calcium-binding proteins or the serotonin 3A receptor

“…Whereas no coexpression of TH with PV, CR or CB is observed in the human cortex, many cortical TH-IR cells coexpress CR in untreated (Asmus et al, 2008) and 6-OHDA-treated (Wachter et al, 2014) rats. Furthermore, the laminar distribution and density of TH-IR cells differs between humans and rodents.…”

“…Furthermore, the laminar distribution and density of TH-IR cells differs between humans and rodents. In humans many of these cells are present in deep cortical layers (Benavides-Piccione and DeFelipe, 2003, 2007; Fukuda et al, 1999; Gaspar et al, 1987; Hornung et al, 1989; Ikemoto et al, 1999; Kuljis et al, 1989; Marui et al, 2003; Raghanti et al, 2009; Trottier et al, 1989), while in rats most TH-IR cells are superficially located (Asmus et al, 2008; Berger et al, 1985; Kosaka et al, 1987a, 1987b). The density of TH-IR neurons appears to be dramatically higher in the human cortex compared to that of rodents (Benavides-Piccione and DeFelipe, 2007).…”

“…Moreover, in all species examined, these TH-IR cells do not contain any subsequent catecholaminergic enzymes (Berger et al, 1985; Gaspar et al, 1987; Ikemoto et al, 1999; Satoh and Suzuki, 1990; Weihe et al, 2006), leaving their end-product in question. In rats TH-IR cells are present in all cortical laminae but are most abundant in layers II/III (Asmus et al, 2008; Berger et al, 1985; Kosaka et al, 1987a, 1987b). Coexpression of CR but not PV or SST was observed in many cortical TH-IR cells in normal rats (Asmus et al, 2008) and in rats treated intraventricularly with the catecholaminergic neurotoxin 6-hydryoxydopamine (6-OHDA) (Wachter et al, 2014).…”

“…In rats TH-IR cells are present in all cortical laminae but are most abundant in layers II/III (Asmus et al, 2008; Berger et al, 1985; Kosaka et al, 1987a, 1987b). Coexpression of CR but not PV or SST was observed in many cortical TH-IR cells in normal rats (Asmus et al, 2008) and in rats treated intraventricularly with the catecholaminergic neurotoxin 6-hydryoxydopamine (6-OHDA) (Wachter et al, 2014). Furthermore, in rats many of the TH-IR somata are adjacent to cortical blood vessels that are outlined by aquaporin-4 (AQP4) (Asmus et al, 2011), which is a channel protein found in the astrocytic end-feet surrounding central nervous system (CNS) microvessels (Tait et al, 2008).…”

“…A subpopulation of neurons in the neocortex of rodents (Asmus et al, 2008, 2011; Berger et al, 1985; Kosaka et al, 1987a, 1987b; Satoh and Suzuki, 1990; Wachter et al, 2014), non-human primates (Raghanti et al, 2009; Weihe et al, 2006), and humans (Benavides-Piccione and DeFelipe, 2003, 2007; Fukuda et al, 1999; Gaspar et al, 1987; Hornung et al, 1989; Ikemoto et al, 1999; Kuljis et al, 1989; Marui et al, 2003; Raghanti et al, 2009; Trottier et al, 1989), is immunoreactive (IR) for tyrosine hydroxylase (TH), the first enzyme in the catecholamine biosynthesis pathway. Cortical TH-IR cells are considered to be inhibitory interneurons because they are small, non-pyramidal cells, many of which coexpress GABA or its biosynthetic enzyme, glutamic acid decarboxylase (GAD).…”