Tyrosine Hydroxylase-like Immunoreactive Neurons Research Articles

Differential expression of AMPA receptor subunits in dopamine neurons of the rat brain: a double immunocytochemical study

We have examined the distribution of dopamine neurons expressing α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits (glutamate receptors 1, 2/3 and 4) in the A8–A15 regions of the rat brain using double immunofluorescence. The distribution of glutamate receptor 1- or 2/3-like immunoreactive neurons completely overlapped that of tyrosine hydroxylase-like immunoreactive neurons in dopamine cell groups in the retrorubral field (A8), the substantia nigra (A9), the ventral tegmental area and the nucleus raphe linealis (A10), and the rostral hypothalamic periventricular nucleus (A14, A15). In the caudal hypothalamic periventricular nucleus (A11), arcuate nucleus (A12) and zona incerta (A13), the distribution was partially overlapping. Neurons double-labeled for tyrosine hydroxylase and glutamate receptor 1 or 2/3 immunoreactivities were, however, exclusively found in certain dopamine cell regions: in areas A14–A15, 85–88% of tyrosine hydroxylase-containing neurons expressed glutamate receptor 1 and 22–25% expressed glutamate receptor 2/3, while in areas A8–A10, 20–43% expressed glutamate receptor 1 and 63–84% expressed glutamate receptor 2/3. In contrast, the double-labeled neurons were hardly detected in the A11–A13 regions. No tyrosine hydroxylase-positive neurons displayed glutamate receptor 4 immunoreactivity, though a partially overlapping distribution of tyrosine hydroxylase- and glutamate receptor 4-immunopositive neurons was also seen in regions A8–10, A11 and A13. The present study has demonstrated the morphological evidence for direct modulation of dopamine neurons via AMPA receptors in rat mesencephalon and hypothalamus. This distribution may provide the basis for a selective dopamine neuron loss in neurodegenerative disorders, such as Parkinson’s disease.

Immunohistochemical localization of tyrosine hydroxylase in the ventral nerve cord of the stick insect, Carausius morosus , including neurons innervating the salivary glands

The distribution of tyrosine hydroxylase-like immunoreactive neurons is mapped in the ventral nerve cord of the stick insect, Carausius morosus. This study also examines the tyrosine hydroxylase- and serotonin-like immunoreactive elements in the salivary glands of Carausius morosus. Tyrosine hydroxylase is the first and rate-limiting enzyme in the pathway for the production of catecholamines; therefore, tyrosine hydroxylase-like immunoreactive neurons are likely to contain catecholamines. Approximately 225 tyrosine hydroxylase-like immunoreactive neurons are present in the ventral nerve cord. The majority of these neurons appear to be interneurons. The suboesophageal ganglion contains the only unpaired neuron and the only pair of peripherally projecting tyrosine hydroxylase-like immunoreactive neurons in the ventral nerve cord. The peripherally projecting neurons project to the salivary glands via the salivary nerve. Each neuron in this pair is termed the salivary neuron 1. The remaining tyrosine hydroxylase-like immunoreactive neurons in the ventral nerve cord are interneurons and exhibit a characteristic distribution within the thoracic and the abdominal ganglia. Serotoninlike immunoreactivity is also present in the salivary glands. Positive staining of the suboesophageal ganglion for serotoninlike immunoreactivity indicates the presence of several neuron pairs including a large pair along the ventral posterior midline that project to the salivary glands via the salivary nerve. Each neuron in this pair is termed the salivary neuron 2. Backfilling of the salivary nerve with cobalt chloride reveals the presence of only two neurons within the suboesophageal ganglion that project to the salivary glands; these neurons are the salivary neurons 1 and 2. Reverse-phase high-performance liquid chromatography coupled with electrochemical detection of ventral nerve cord and salivary gland homogenates confirms the presence of dopamine and serotonin.

Catecholaminergic neurons in the nucleus tractus solitarii which send their axons to the naidbrain periaqueductal gray express Fos protein after noxious stimulation of the stomach: a triple labeling study in the rat

In rats which were injected with horseradish peroxidase (HRP) into the midbrain periaqueductal gray (PAG) and then administered with formaldehyde into the stomach, Fos-like immunoreactivity was found in tyrosine hydroxylase-like immunoreactive neurons in the nucleus tractus solitarii (NTS) which were retrogradely labeled with HRP. The results indicate that catecholaminergic NTS neurons may mediate nociceptive visceral information to the PAG.

Chronic nicotine treatment counteracts nigral cell loss induced by a partial mesodiencephalic hemitransection: An analysis of the total number and mean volume of neurons and glia in substantia nigra of the male rat

This study combines immunocytochemical and stereological methods for the first time to obtain unbiased estimates of the number of cells in the entire substantia nigra and their respective mean volume. Nicotine, delivered by subcutaneously implanted osmotic pumps (0.125mg/kg/h, 14 days) to male Sprague-Dawley rats with a partial unilateral mesodiencephalic lesion, caused a significant counteraction of the lesion-induced reduction in total number of nigral tyrosine hydroxylase-like immunoreactive neurons counterstained with Cresyl Violet compared with saline treated control animals. The number of Nissl stained neurons without tyrosine hydroxylase-like immunoreactivity was not affected by the lesion nor by nicotine. The numbers of non-neuronal glial fibrillary acidic protein-like immunoreactive cells counterstained with Cresyl Violet and smaller cells seen after Cresyl Violet staining alone, possibly representing microglia, were increased by the lesion but not affected by nicotine. No nicotine-induced effects were found on the number of nigral cells located contralateral to the lesion. The lesion-induced reduction in the mean volume of the nigral cells showing tyrosine hydroxylase-like immunoreactivity, as determined with the stereological rotator method, was not affected by nicotine. These findings suggest that continuous nicotine infusion exerts protective effects on lesioned nigroneostriatal dopamine systems and that these protective effects are selective for the nigral dopamine neurons not affecting other populations of neurons or non-neuronal cells. This neuroprotective effect might lead to new therapeutic strategies in clinical neurodegenerative disorders such as Parkinson's Disease.

Substance P‐ and tyrosine hydroxylase‐ containing neurom in the human dorsal motor nucleus of the vagus nerve

The aim of this study was to provide a comprehensive account of the topography, morphology, and frequencies of the substance P- and tyrosine hydroxylase-containing neurons in the human dorsal motor nucleus of the vagus nerve. The morphology of immunoreactive neurons was studied and the variations of the cell distributions were presented by three-dimensional computer reconstructions. Three types of substance P-like immunoreactive neurons were identified. They were predominantly located in the dorsointermediate, centrointermediate, caudointermediate, and caudal division of the dorsal motor nucleus of the vagus nerve. The morphology of substance P-like immunoreactive neurons varied according to the subnuclei in which they were found. Three types of tyrosine hydroxylase-like immunoreactive neurons were identified, mainly in the periphery of the dorsal motor nucleus of the vagus nerve, including the medial fringe, ventrointermediate, and dorsointermediate subnuclei of the 10. Many cells throughout the ventrointermediate subnucleus of the dorsal motor nucleus of the vagus nerve are seen ventrally to intermingle with the tyrosine hydroxylase neurons of the intermediate reticular zone. Computer reconstructions provided a three-dimensional view of the positions of substance P- and tyrosine hydroxylase-like immunoreactive neurons within the subdivisions of the dorsal motor nucleus of the vagus nerve. The uneven distribution of substance P- and tyrosine hydroxylase-like immunoreactive neurons within the subdivisions suggests an involvement of these substances in some, but not all, autonomic functions of the dorsal motor nucleus of the vagus nerve.

Localization of NADPH diaphorase activity in monoaminergic neurons of the rat brain

Nitric oxide has recently been implicated as a neurotransmitter, and may modulate synaptic transmission, cerebral blood flow, and neurotoxicity. NADPH diaphorase histochemistry has been shown to be a reliable marker for nitric oxide synthase, the enzyme that synthesizes nitric oxide, in the nervous system. Because monoaminergic neurons frequently contain co-transmitters, we examined whether these cells also exhibit NADPH diaphorase activity. Frozen sections from postnatal and adult rat brains were stained for NADPH diaphorase activity and either serotonin-like immunoreactivity or tyrosine hydroxylase-like immunoreactivity. Numerous neurons in the mesopontine serotoninergic cell groups (including the caudal linear, dorsal, median, supralemniscal, and pontine raphe nuclei) contained both serotonin-like immunoreactivity and NADPH diaphorase activity. Within the dorsal raphe nucleus, approximately 70% of the serotoninergic neurons in the medial subnuclei displayed NADPH diaphorase activity, while less than 10% of the serotoninergic neurons in the lateral subnuclei were doubly labeled. Retrograde labeling with fluorescent microspheres indicated that many raphe-cortical neurons contained NADPH diaphorase activity. No NADPH diaphorase activity was detected in serotoninergic neurons in the medullary nuclei (including the raphe magnus, raphe pallidum, and raphe obscurus). Only a small proportion of tyrosine hydroxylase-like immunoreactive neurons in the periaqueductal gray, rostral linear nucleus, and rostrodorsal ventral tegmental area contained NADPH diaphorase activity. Tyrosine hydroxylase-like immunoreactive neurons in the substantia nigra, locus coeruleus, hypothalamus, olfactory bulb, and dorsal raphe nucleus did not contain detectable NADPH diaphorase activity. The observation that many mesopontine (but not medullary) serotoninergic neurons contain NADPH diaphorase activity suggests that these neurons may release both serotonin and nitric oxide.

Serotonin-, substance P- and tyrosine hydroxylase-like immunoreactive neurons projecting from the midbrain periaqueductal gray to the nucleus tractus solitarii in the rat

Serotonin-, substance P- and tyrosine hydroxylase-like immunoreactive neurons in the midbrain periaqueductal gray (PAG) were observed to send their axons to the nucleus tractus solitarii in the rat by the retrograde horseradish peroxidase tracing method combined with the immunocytochemical technique. These neurons were most frequently observed in the ventrolateral subnucleus and ventral portion of the medial subnucleus of the PAG at the entire rostrocaudal levels.

Immunohistochemical evidence for coexistence of methionine-enkephalin and tyrosine hydroxylase in neurons of the locus coeruleus complex projecting to the spinal cord of the cat

Previous studies have revealed the presence of pontospinal neurons with either methionine-enkephalin-or tyrosine hydroxylase-like immunoreactivity in the dorsolateral pontine tegmentum of the cat. Using a combined fast blue retrograde transport technique and simultaneous immunofluorescence histochemistry, the present study was designed to reveal the coexistence of enkephalin and tyrosine hydroxylase in cat coerulospinal neurons and to determine if and to what extent the coerulospinal pathway is heterogeneous. Fast blue-labelled neurons with tyrosine hydroxylase- and enkephalin-like immunoreactivities were found in the nucleus locus coeruleus, nucleus subcoeruleus, Kölliker-Fuse nucleus, and the medial and lateral parabrachial nuclei. Approximately 87% of tyrosine hydroxylase-like immunoreactive neurons had enkephalin-like immunoreactivity, whereas about 76% of the enkephalin-like immunoreactive neurons had tyrosine hydroxylase-like immunoreactivity. About 71% of all coerulospinal neurons exhibited both tyrosine hydroxylase- and enkephalin-like immunoreactivities. These findings indicate that coerulospinal activity may lead to spinal cord effects reflecting both norepinephrine and enkephalin activity in most cases but do not rule out each transmitter's isolated functions.

Serotonin-, substance P- and tyrosine hydroxylase-like immunoreactive neurons projecting from the periaqueductal gray to the ventromedial hypothalamic nucleus in the rat

Direct projections from serotonin-, substance P- and tyrosine hydroxylase-like immunoreactive neurons in the midbrain periaqueductal gray (PAG) to the ventromedial hypothalamic nucleus (VMH) in the rat were investigated by the retrograde horseradish peroxidase tracing method combined with the immunocytochemical technique. Serotonin-, substance P- and tyrosine hydroxylase-like immunoreactive PAG neurons sending their axons to the VMH were distributed in the ventrolateral subnucleus and ventral portion of the medial subnucleus of PAG at the middle and caudal levels.

Tyrosine hydroxylase-like immunoreactive neurons in the olfactory bulb of the snake, Elaphe quadrivirgata, with special reference to the colocalization of tyrosine hydroxylase- and GABA-like immunoreactivities

The distribution and structural features of tyrosine hydroxylase-like immunoreactive (TH-LI) neurons were studied in the olfactory bulb of a snake, Elaphe quadrivirgata, by using pre- and post-embedding immunocytochemistry at the light microscopic level. In contrast to rodent olfactory bulbs previously reported, many TH-LI neurons were seen not only in the main olfactory bulb (MOB) but also in the accessory olfactory bulb (AOB). With regard to the TH-like immunoreactivity, there appeared no appreciable differences between MOB and AOB. As in mammalian MOB, the majority of TH-LI neurons were clustered in the periglomerular region and appeared to send their dendritic branches into glomeruli, which as a whole make an intense TH-LI band in the glomerular layer (GML). In the external plexiform/mitral cell layer (EPL/ML) of MOB and AOB as well as in the outer sublamina of the internal plexiform layer (OSL) of AOB, an appreciable number of TH-LI neurons were scattered, extending dendritic processes which appeared to make a loose meshwork. TH-LI neurons in EPL/ML (including OSL) appeared to consist of at least two morphologically different types. The first had a small perikaryon and one or two smooth dendrites which usually extended to GML and were frequently confirmed to enter into glomeruli. The second had a larger perikaryon and 2-3 dendrites which branched into several varicose processes extending in EPL/ML/OSL but appeared not to enter into glomeruli. The TH-like immunoreactivity was rarely seen in the internal plexiform layer and internal granule cell layer. The colocalization of GABA-like and TH-like immunoreactivities was further studied. Almost all TH-LI neurons in both EPL/ML/OSL and GML contained GABA-like immunoreactivity irrespectively of the type of TH-LI cells.

Fine Structure of Tyrosine Hydroxylase-like Immunoreactive Neurons and Terminals of the Hypothalamic Arcuate Nucleus and Median Eminence in Young and Aged Rats

Tyrosine hydroxylase (TH)-like immunoreactive neurons, fibers, and terminals in the hypothalamic arcuate nucleus and median eminence of young (8 weeks old) and aged (24 months old) rats were investigated at light and electron microscopic levels by means of the peroxidase anti-peroxidase (PAP) method. In the arcuate nucleus, TH-like immunoreactive neuronal perikarya of young animals contained well-developed cell organelles such as rough-surfaced endoplasmic reticulum (rER), mitochondria, Golgi apparatus, polysomes, as well as dense granules. Immunoreactive neuronal elements appeared as both presynaptic and postsynaptic elements. In aged rats, TH-like immunoreactive neuronal perikarya as well as non-immunoreactive ones were found to include many lysosomes or inclusions, and many neuronal elements with degradative changes were observed. In the external layer of the median eminence of young animals, many immunoreactive nerve endings were found around the pericapillary spaces of portal vessels and often terminated adjacent to the basement membranes of the pericapillary spaces. Immunoreactive fibers having close contact with non-immunoreactive fibers were also observed. In aged animals, degradative changes such as axons with swollen and watery appearance and myelin figures were observed in the neuronal elements, although many immunoreactive nerve endings were seen around the pericapillary spaces.

Increase of tyrosine hydroxylase-like immunoreactive neurons in the nucleus accumbens and the olfactory bulb in the rat with the lesion in the ventral tegmental area of the midbrain

A small number of neurons in the nucleus accumbens of the rat showed tyrosine hydroxylase-like immunoreactivity (TH-LI). These TH-LI neurons had medium-sized cell bodies with several spiny dendrites. When a lesion was produced in the ventral tegmental area of the midbrain by injecting 6-hydroxydopamine, TH-LI neurons in the nucleus accumbens, as well as those in the olfactory bulb, were increased in number on the side ipsilateral to the lesion. The results indicated that expression of TH might be enhanced in some neurons deprived of dopaminergic afferent fibers.

Distribution of neuropeptide Y-like immunoreactive perikarya and processes in the medulla of the cat

Neuropeptide Y-like immunoreactive (NPY-LI) perikarya and processes have been identified in the medulla of the cat. NPY-LI perikarya were found in 4 regions; (1) the medial N. of the solitary tract (MNTS), (2) the lateral tegmental field (LTF), (3) the ventrolateral medullary surface (VLMS), and (4) in the spinal trigeminal nucleus. Tyrosine hydroxylase-like immunoreactive (TH-LI) neurons were also found in the first 3 regions noted above. NPY-LI and TH-LI neurons had a similar morphology and distribution. NPY-LI and TH-LI neurons were counted in sections from 3 representative levels of the medulla. NPY-LI cells were most numerous in the LTF, especially at the level of the area postrema and more rostrally. The lowest number of NPY-LI cells was seen in the MNTS, particularly at a level caudal to the area postrema. NPY-LI cells were at least 3-fold less numerous than TH-LI cells at all levels of the MNTS, but there was a 27-fold greater number of TH-LI neurons at a level of MNTS caudal to the area postrema. In the LTF, NPY-LI cells were 2- to 5-fold less common than TH-LI cells. Approximately equal numbers of NPY-LI and TH-LI cells were counted in the VLMS at the level of the area postrema and rostrally. These data indicate that the majority of TH-LI cells in the MNTS of the cat probably do not contain NPY as a co-transmitter.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of catecholaminergic projections to the spinal cord in the North American opossum, Didelphis virginiana

The intent of our study was to determine when catecholaminergic axons grow into each of their adult targets in the spinal cord of the North American opossum (Didelphis virginiana) and to identify the origin of catecholaminergic axons in the lumbosacral cord at different stages of development. Tyrosine hydroxylase-like immunoreactive axons, presumed to be catecholaminergic, were demonstrated at different stages of development by the indirect antibody peroxidase-antiperoxidase technique of Sternberger. The neurons giving rise to such axons in the lumbosacral cord were identified by using the retrograde transport of Fast Blue and immunofluorescence for tyrosine hydroxylase-like immunoreactive neurons. At birth, 12-13 days after conception, tyrosine hydroxylase-like immunoreactive axons are present in the marginal zone throughout the length of the spinal cord. Such axons are particularly numerous in the dorsolateral marginal zone, the region containing most of them in adult animals. By postnatal day 3, a few immunoreactive axons are present in the intermediate (mantle) zone of the spinal cord; and by postnatal day 8, they are most concentrated in the presumptive intermediolateral cell column. Laminae I and II of the dorsal horn are not innervated by such axons until approximately postnatal day 15. By postnatal day 44, the distribution of tyrosine hydroxylase-like immunoreactive axons in the spinal cord resembles that in adult animals, although some areas may be hyperinnervated. At birth, tyrosine hydroxylase-like immunoreactive cell bodies are present in all of the brainstem areas providing catecholaminergic projections to the spinal cord in adult animals (Pindzola et al.: Brain Behav. Evol. 32:281-292, '88); and by at least postnatal day 5, lumbosacral injections of Fast Blue retrogradely label tyrosine hydroxylase-like immunoreactive neurons in all such areas. Retrogradely labeled immunoreactive neurons were also found in areas that do not contain them in adult animals. Such areas include the dorsal part of the nucleus coeruleus and certain areas of the reticular formation. During development, spinally projecting tyrosine hydroxylase-like immunoreactive neurons are numerous medial to the nucleus ventralis lemnisci lateralis (the paralemniscal region), whereas only a few are present in the same location in adult animals. Our results suggest that catecholaminergic axons grow into the spinal cord prenatally, that they innervate their adult targets postnatally and over an extended time period, and that during some stages of development they originate from areas that do not supply them in the adult animal.

Tyrosine hydroxylase-like immunoreactive neurons in the striatum of the rat

Striatal neurons exhibiting tyrosine hydroxylase-like immunoreactivity (TH-LI) were found in the adult rat. Most of these neurons had a cell body with a 10–20 μm diameter and several spiny dendrites. The number of striatal neurons with TH-LI was increased on the side ipsilateral to an electrothermic or 6-hydroxydopamine-induced lesion which had been placed in the regions around the substantia nigra.

Tyrosine hydroxylase-like and dopamine β-hydroxylase-like immunoreactivity in the gustatory zone of the nucleus of the solitary tract in the hamster: Light- and electron-microscopic studies

A quantitative electron-microscopic analysis has been conducted on the neurons within the gustatory zone of the nucleus of the solitary tract of the hamster. The most common group of neurons within the gustatory zone contains both large (X1) and small (X3) members that possess deeply invaginated nuclear profiles. These neurons have somal areas that average 113μm 2 (range 34–281 μm 2) and a value of somal area/nuclear area that averages 2.2. Other large and small neurons that have non-invaginated nuclear profiles are also observed. The larger (X2) neurons average 151μm 2 (range 49–487μm 2) and have much cytoplasm and associated membranous organelles that is reflected in a mean value of somal area/nuclear area of 2.6. Members of the X2 group are the largest neurons in the gustatory zone. The smaller (X4) group contains the smallest neurons in the gustatory zone of the nucleus of the solitary tract, averages 5μm 2 (range 16–103μm 2), shows almost no perinuclear cytoplasm and has a mean value of somal area/nuclear area of only 1.5. These findings are consistent with and expand upon the results of similar studies at the light-microscopic level. This grouping has been used to explore the association of tyrosine hyroxylase-like and dopamine β-hydroxylase-like immunoreactivities with specific populations of neurons that are known to be distributed across the various levels of the gustatory zone. At the light-microscopic level, numerous well-defined and intensely labelled tyrosine hydroxylase-like immunoreactive somata of various morphologies and sizes are observed. Quantification at the electron-microscopic level indicates that 10–15% of the neurons encountered in the dorsal and intermediate levels of the gustatory zone are immunoreactive. The ventral level of the gustatory zone contains few immunoreactive neurons. Tyrosine hydroxylase-like immunoreactive neurons possess either non-invaginated or invaginated nuclear profiles and their somal areas average 106 and 142μm 2, respectively. On the bases of size and ultrastructural features, these immunoreactive somata are assigned to the two groups (X1 and X2) of large neurons within the gustatory portion of the nucleus of the solitary tract. In general, small neurons are not immunoreactive. The distribution of dopamine β-hydroxylase-like immunoreactivity has also been examined in adjacent sections in order to reveal the presence of any putative noradrenergic neurons in the gustatory zone. Such immunoreactive neurons are uncommon, implying a low level of conversion of dopamine to norepinephrine. These results are compared to those from the rat because the locations of catecholamine cell groups in the rat's brainstem have been well documented. The rat expresses fewer tyrosine hydroxylase-like immunoreactive neurons in the gustatory zone than the hamster but similar and also low numbers of dopamine β -hydroxylase-positive neurons. In the rat and hamster, the caudal portion of the nucleus of the solitary tract that is included in the A2 noradrenergic cell group contains a substantial number of tyrosine hydroxylase-like immunoreactive somata and more modest numbers of dopamine β -hydroxylase-like immunoreactive somata. Caudally, both types of immunoreactivities are greater than that seen in the gustatory zone and are greater in the rat than in the hamster. These studies quantify for the first time in the hamster the ultrastructural features of morphologically distinct groups of neurons that are in a position to process peripheral gustatory activity. In addition, a unique distribution of tyrosine hydroxylase-like immunoreactive somata in the gustatory zone of the nucleus of the solitary that may reflect dopamine has been associated with particular groups of neurons. This population of putative dopaminergic neurons is more substantial in the hamster than in the rat and is located in a portion of the nucleus of the solitary tract that is not included in the A2 catecholamine cell group of the dorsomedial medulla. The finding that putative dopaminergic neurons are located in the rostral pole of the nucleus of the solitary tract, together with previous findings that many neurons of the gustatory zone have intrinsic caudal projections and that the caudal part of the nucleus also contains dopaminergic neurons, suggests interactions between adjacent regions concerned primarily with ingestional and autonomic functions.

Transient tyrosine hydroxylase-like immunoreactive neurons contain somatostatin and substance P in the developing amygdala and bed nucleus of the stria terminalis of the rat

Tyrosine hydroxylase-like immunoreactive (TH-IR) neurons were observed from the embryonic day 17 (E17) to 6 weeks postnatally in two closely related nuclei of the limbic system, the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CNA) where they were restricted to circumscribed zones. These cells were scarce with an immature morphological aspect at E17. They progressively differentiated and increased in number until postnatal day 5 (P5), when their maximal density was reached. They were characterized as neurons by their ultrastructural appearance and the presence of both axo-somatic and axo-dendritic synaptic junctions. Moreover, TH-IR axons could be followed in the stria terminalis leaving the CNA, suggesting that part of TH-IR cells could be long projecting neurons rather than interneurons. A gradual decrease in the intensity of TH-IR and in density of labeled neurons was noted from P15 on, in both nuclei, (−50% at 4 weeks) until their total disappearance at 7 weeks. The significance of this TH-IR labeling regarding the catecholaminergic transmission remains unclear since these neurons did not contain the other catecholaminergic synthetic enzymes (DOPA-decarboxylase, dopamine-β-hydroxylase, phenylethanolamine- N-methyl transferase) nor endogenous catecholamines. Double-labeling immunocytochemical methods, indicated that almost all the TH-IR neurons were colocalized with somatostatin 28 (SST) and with substance P (SP). Therefore these neurons expressed simultaneously 3 phenotypes, TH, SST and SP. This observation brings forth the notion of multiple neurotransmitter expression in transient neuronal populations and raises the question of neurotransmitter plasticity in the late postnatal development of the central nervous system (CNS). These neurons which were observed in two closely interconnected structures could be involved in early limbic circuits.

Tyrosine hydroxylase-immunoreactive neurons in the human cerebral cortex: a novel catecholaminergic group?

Tyrosine hydroxylase-like immunoreactive (TH-IR) neurons with morphological features of interneurons were found throughout the human cerebral cortex. Quantitative estimates in 14 different cytoarchitectonic areas revealed a specific regional distribution pattern, neurons being less dense in primary cortical areas and denser in higher order associative areas and some limbic related areas. A partial relationship was noted between the density of labeled neurons and that of the known dopaminergic innervation. The role of the cortical TH-IR neurons in catecholaminergic function, however, remains unclear since the presence of other catecholaminergic synthesizing enzymes, dopamine-β-hydroxylase and DOPA decarboxylase, could not be demonstrated at their level. Similar neurons have been observed transiently in the rodent cortex during development; their persistence and topographical extension in the human brain warrants further study on their possible functional role.

Transient expression of tyrosine hydroxylase immunoreactivity in some neurons of the rat neocortex during postnatal development.

Tyrosine hydroxylase-like immunoreactive neurons were observed in the dorsolateral and medial neocortex of the rat during postnatal development. They occurred from 8 up to 24 days of age and lacked other catecholamine synthetizing enzymes. They appeared to be insensitive to the suppression of cortical noradrenergic innervation induced by neonatal subcutaneous injections of 6-hydroxydopamine.

Morphology and distribution of tyrosine hydroxylase-like immunoreactive neurons in the cat retina.

In cat retina, antisera directed against tyrosine hydroxylase (tyrosine 3-monooxygenase; EC 1.14.16.2) labeled three morphologically distinct classes of neurons; amacrine cells, displaced amacrine cells, and interplexiform cells. These three cell populations differed not only in their morphologies but also in their numbers, densities, and retinal distributions. Insofar as tyrosine hydroxylase-like immunoreactivity is associated with dopaminergic neurons, these observations suggest that the dopamine system in cat retina is morphologically heterogeneous and that the cat retina contains functional subdivisions based on the different distributions of specific cell populations.