Development of the rat thalamus: II. Time and site of origin and settling pattern of neurons derived from the anterior lobule of the thalamic neuroepithelium

Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to examine the time of origin, settling pattern, and neuroepithelial site of origin of the anterior thalamic nuclei--the lateral dorsal (lateral anterior), anterodorsal, anteroventral and anteromedial nuclei--and of two rostral midline structures--the anterior paraventricular and paratenial nuclei. The neurons of the lateral dorsal nucleus are generated over a 3-day period between days E14-E16 and their settling pattern displays a combined lateral-to-medial and dorsal-to-ventral neurogenetic gradient. The bulk of the neurons of the anteroventral nucleus are generated over a 3-day period between days E15-E17 and settle with an oblique lateral-to-medial and ventral-to-dorsal neurogenetic gradient. The bulk of the neurons of the anteromedial nucleus are generated over a 2-day period between days E16-E17 and show the same settling pattern as the anteroventral nucleus. The neurons of the anterodorsal nucleus are generated over a 3-day period between days E15-E17 and show a lateral-to-medial neurogenetic gradient. The bulk of the neurons of the central part and lateral part of the paraventricular nucleus are generated over a 2-day period (E16-E17 and E17-E18, respectively) and each part displays a ventral-to-dorsal neurogenetic gradient. Finally, the bulk of the neurons of the paratenial nucleus are generated over a 4-day period between days E15-E18 and settle with a lateral-to-medial neurogenetic gradient. Observations are presented that the anterior thalamic nuclei, constituting the distinct "limbic thalamus," derive from a discrete neuroepithelial source. This is the crescent-shaped germinal matrix lining the diencephalic (medial) wall of the hitherto unrecognized anterior transitional promontory, which we call the anterior thalamic neuroepithelial lobule. On day E16 three migratory streams leave the anterior neuroepithelial lobule and, on the basis of their labeling pattern in relation to the neurogenetic gradients of the anterior thalamic nuclei, they are identified, from dorsal to ventral, as the putative migratory streams of the anterodorsal, anteroventral, and lateral dorsal nuclei. On day E17 the putative migratory stream of the anteromedial nucleus appears to leave the same neuroepithelial region that on the previous days was the source of the anteroventral nucleus. Dorsally, two neuroepithelial patches persist after day E17 and these are identified as the putative cell lines of the anterior paraventricular and paratenial nuclei.     

An autoradiographic study of the time of final division of neurons in rat hypothalamic nuclei

An autoradiographic study of the development of 26 nuclei in the rat hypothalamus was made by injecting pregnant rats on different days of pregnancy with tritiated thymidine. The offspring were killed postnatally and the day of gestation on which peak percentages of heavily labeled neurons occurred was considered to be the birthdate of that nucleus. Postnatal animals for the first nine days were injected and were also included in the study. Laterally placed nuclei were found to arise on the fourteenth day of gestation while medial nuclei, in general, arose on day 16. Final cell divisions occurred over a period of time but the majority took place on the days indicated. Apparently a lateromedial gradient exists in the hypothalamus, and possibly a dorsoventral gradient.     

Development of the brain Stem in the rat. II. Thymidine-radiographic study of the time of origin of neurons of the upper medulla,excluding the vestibular and auditory nuclei

Groups of pregnant rats were injected with two successive daily doses of ³H-thymidine from gestational days 12 and 13 (E12 + 13) until the day before birth (E21 + 22). In radiographs from adult progeny of these rats the proportion of neurons generated on specific days was determined in the major nuclei of the upper medulla, with the exception of the vestibular and auditory nuclei. The neurons of the motor nuclei are generated over a brief period. Neurons of the retrofacial nucleus are produced first, with more than 60% of the cells arising on day E11 or earlier. Peak generation time of abducens neurons is day E12 and of the neurons of the facial nucleus is day E13. In contrast, the neurons of the superior salivatory nucleus are produced late, predominantly on day E15 and some on day E16. The generation of the (sensory relay) neurons of the nucleus oralis of the trigeminal complex takes place over an extended period between days E12 and E15; the last generated cells include the largest neurons of this nucleus. Neurons of the raphe magnus are produced between days E11 and E14, the neurons of the rostral medullary reticular formation between days E12 and E15. The latest generated neurons of the upper medulla (excluding the cochlear nuclei) belong to a structure identified as the granular layer of the raphe. Combining these results with those of the preceding paper (Altman and Bayer, ′80a) and with additional data, it is postulated that the laterally and ventrally situated motor nucleus of the trigeminal, the facial nucleus, and the nucleus ambiguus form a single longitudinal zone of branchial motor neurons with a rostral-to-caudal cytogenetic gradient. In contrast, the medially and dorsally situated (juxtaventricular) hypoglossal nucleus and abducens nucleus (together with the other nuclei of the ocular muscles) form a longitudinal somatic motor zone with a caudal-to-rostral gradient. The dorsal nucleus of the vagus and the superior salivatory nucleus may constitute a preganglionic motor zone, also with a caudal-to-rostral cytogenetic gradient.     

Neurogenesis of the magnocellular basal forebrain nuclei in the rhesus monkey

The time of origin of the neurons that comprise the magnocellular basal forebrain nuclei in rhesus monkeys was determined by using [3H]thymidine autoradiography. Thirteen pregnant animals received an injection of [3H]thymidine between embryonic days 27 (E27) and E50 of their 165 day gestation, and their offspring were sacrificed during the early postnatal period. Neurons within this region were generated in a biphasic pattern. An initial burst of [3H]thymidine-labeled magnocellular neurons was first observed throughout short quiescent period, cells of the remaining anterior basal forebrain (inclusive of magnocellular neurons comprising the vertical limb of the diagonal band and the anteromedial and anterolateral regions of the nucleus basalis) were generated between E36 and E45 with a peak of neurogenesis seen on E40-E43. The intermediate division of the nucleus basalis was generated about the same time, but the peak period of neurogenesis in this region occurred slightly earlier (E36 and E40) and was completed by E43. During the second phase of neurogenesis, neurons within the posterior division of the basal forebrain were generated first, with their genesis virtually completed between E33 and E36. The genesis of all neurons comprising the magnocellular basal forebrain nuclei was completed by E48 of gestation. A general caudal to rostral gradient of neurogenesis was observed within this telencephalic region. In contrast, a neurogenic gradient was not discerned in the radial direction. The present data demonstrate that neurons comprising the basal forebrain magnocellular nuclei in monkeys are generated early in gestation with two peak times of neuronal genesis. These nuclei are among the earliest to be generated in the entire telencephalon, which, like neurons of the thalamus and cortical neurons giving rise to cortical-cortical connections, places them in a strategic position to potentially influence their target neurons within the cortical mantle that are generated later in gestation.     

Development of the brain stem in the rat. V. Thymidine-radiographic study of the time of origin of neurons in the midbrain tegmentum

Groups of pregnant rats were injected with two successive daily doses of ³H-thymidine from gestational day E12 and 13 (E12 + 13) until the day before parturition (E21 + 22) in order to label in their embryos the proliferating precursors of neurons. At 60 days of age the proportion of neurons generated (no longer labeled) on specific embryonic days was determined quantitatively in 18 regions of the midbrain tegmentum. The neurons of the oculomotor and trochlear nuclei are generated concurrently on days E12 and E13. There was a mirror image cytogenetic gradient in these nuclei and this was interpreted as the dispersal of neurons derived from a common neuroepithelial source to the medial longitudinal fasciculus. Neurons in three other components of the tegmental visual system are produced in rapid succession after the motor nuclei. In the nucleus of Darkschewitsch peak production time was on days E12 and E13, extending to day E15; in the Edinger-Westphal nucleus the time span was the same but with a pronounced peak on day E13; finally, the neurons of the parabigeminal nucleus were produced between days E13 and E15 with a peak on day E14. The neurons of the periaqueductal gray were generated between days E13 and 17 with a pronounced ventral-to-lateral and lateral-to-dorsal gradient. In the red nucleus the neurons were produced on days E13 and E14 with a caudal-to-rostral gradient: the cells of the magnocellular division preceding slightly but significantly the cells of the parvocellular division. The neurons of the interpeduncular nucleus originated between days E13 and E15; the peak in its ventral portion was on day E13, in its dorsal portion on days E14 and E15. A ventral-to-dorsal gradient was seen also in both the dorsal and the median raphe nuclei in which neuron production occurred between days E13 and E15. The neurons of the pars compacta and pars reticulata of the substantia nigra were both produced between days E13 and E15 with a modified lateral-to-medial gradient. This gradient extended to the ventral tegmental area where neurons of the pars medialis were produced between days E14 and E16. With the exception of the central gray, neuron production was rapid and relatively early in the structures situated ventral to the midbrain tectum. A comparison of the cytogenetic gradients in the raphe nuclei of the lower and upper medulla, the pontine region, and the midbrain suggests that they originate from at least three separate neuroepithelial sources.     

Time of neuron origin in mouse hypothalamic nuclei

In order to elucidate the time of origin of the neurons in mouse hypothalamic nuclei, tritiated thymidine, a radioactive precursor of DNA, was given to the pregnant mice on different days of gestation. Offsprings were killed postnatally and the coronal sections through various parts of the hypothalamus were processed for autoradiography. Subsequently, distributions of heavily labeled neurons in the hypothalamus were reconstructed in the maps. The neurons in the mouse hypothalamus are formed between days 10 and 16 of embryonic life with most neurons being formed between days 11 and 14. The neurons in the laterally placed nuclei are produced earlier than are those in the medially placed nuclei. It is clearly demonstrated that a lateromedial gradient exists at the time of origin in mouse hypothalamic neurons. There also seem to be medioanterior and medioposterior gradients and a dorsoventral gradient.     

Genesis of neurons in the dorsal lateral geniculate nucleus of the cat

Neurons that will ultimately form the dorsal and ventral lateral geniculate nuclei, the medial interlaminar nucleus, the perigeniculate nucleus, and the nucleus reticularis of the cat undergo their final cell division beginning on, or slightly before, embryonic day 22 (E22) and ending on, or before, E32. Early in this period, neurogenesis proceeds for all of these geniculate nuclei, whereas only in the dorsal lateral geniculate nucleus does cell birth continue until E32. Distinct spatiotemporal gradients of cell birth are not obvious within any of the individual geniculate nuclei. For the dorsal lateral geniculate nucleus in particular, and for the other geniculate nuclei in general, neurons born early in this period exhibit a full range of adult soma sizes, including large and small neurons. Neurons born late in this period exhibit only small adult somas. The location and size of a neuron within the dorsal lateral geniculate nucleus provide clues to that cell's functional properties. On the basis of presently available information regarding the relationship between structure and function of neurons in the cat's dorsal lateral geniculate nucleus, the findings described here suggest that all functional classes of neurons in the dorsal lateral geniculate nucleus are born at the same time throughout most of this period.     

Development of the diencephalon in the rat. V. Thymidine-radiographic observations on internuclear and intranuclear gradients in the thalamus.

Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational days 13 and 14 (E13 + 14) until the day before birth (E21 + 22). Internuclear and intranuclear cytogenetic gradients were examined in radiograms of the thalamus sectioned in the coronal, sagittal and horizontal planes. There was a precise and segregated lateral-to-medial gradient between and within the habenular nuclei. In the ventral thalamus the reticular nucleus had a lateral-to-medial gradient, the subthalamic nucleus a laterodorsal-to-medioventral gradient. There was a caudal-to-rostral gradient between the medial geniculate and dorsal lateral geniculate nuclei, and between the pars posterior and pars anterior of the lateral nucleus. A clear intranuclear gradient could not be detected in the sensory relay nuclei with the exception of the medial geniculate nucleus. A lateral-to-medial internuclear gradient was seen between the relay nuclei and the intralaminar nuclei, and between the latter and some of the midline nuclei. On the basis of a consideration of the time of origin and time span of production of neurons of various thalamic nuclei, and taking into account some of the recognizable internuclear and intranuclear gradients, the thalamus was divided into five principal cytogenetic components; the epithelamus, the ventral thalamus, the dorsal thalamus, the medial thalamus, and the posterior thalamus. The epithalamic nuclei form over a protracted period resembling the nuclei of the hypothalamus. The nuclei of the ventral thalamus are generated early and over a relatively long period. The dorsal thalamus consists of the relay nuclei and the intralaminar nuclei; they form rapidly and ahead of the medial thalamus. The medial thalamus was subdivided into the earlier-forming anteromedial nuclei and the latest-forming midline nuclei. The posterior thalamus was not examined in detail.     

Development of the brain stem in the rat. III. Thymidine-radiographic study of the time of origin of neurons of the vestibular and auditory nuclei of the upper medulla

Groups of pregnant rats were injected with two successive daily doses of ³H-thymidine form gestational days 12 and 13 (E12 + 13) until the day before parturition (E21 + 22). In adult progeny of the injected rats the proportion of neurons generated on specific embryonic days was determined quantitatively in the vestibular and auditory nuclei of the upper medulla. In the vestibular nuclei, neurons are generated between days E11 and E15 in an overlapping sequential order, yielding a lateral-to-medial and a rostral-to-caudal internuclear gradient. In the lateral vestibular nucleus peak production time is day E12; in the superior nucleus, E13; in the inferior nucleus, E13 and E14; and in the medial nucleus, E14. The early generation of neurons of the lateral vestibular nucleus may reflect the early differentiation of the circuit from the gravity receptors (utricle) to neurons of the spinal cord controlling postural balance. The later production of neurons of the superior vestibular nucleus may reflect the subsequent differentiation of the circuit from the rotational receptors (semicircular canals) to the neurons of the brain stem controlling eye movements. The generation time of neurons of the nucleus prepositus hypoglossi overlaps with that of the medial vestibular nucleus. The neurons of the anteroventral and posteroventral cochlear nuclei are produced form days E13 to E17, with no temporal differences between the two nuclei. The neurons of the dorsal cochlear nucleus are generated over a very long time span, beginning on day E12 and extending into the postnatal period. There is a sequence in the production of neurons forming the different layers of the dorsal cochlear nucleus in the following order: pyramidal cells, cells of the inner layer, cells of the outer layer and, finally, cells of the granular layer. There is also a sequential production of neurons in four nuclei of the superior olivary complex. In the lateral trapezoid nucleus peak production time is day E12; in the medial superior olivary nucleus, day E13; in the medial trapezoid nucleus, day E15; and in the lateral superior olivary nucleus, day E16. This order yields a medial-to-lateral gradient in the dorsal aspect of the superior olivary complex, and a lateral-to-medial gradient ventrally. These mirror-image gradients were also seen intranuclearly in the lateral superior olivary nucleus and the medial trapezoid nucleus. The cytogenetic gradients could not be related to tonotopic representation; however, they could be related to the lateral location of ipsilateral cochlear nucleus input to the lateral superior olivary nucleus and the medial location of the contralateral cochlear nucleus input to the medial trapezoid nucleus.     

Development of the diencephalon in the rat. IV. Quantitative study of the time of origin of neurons and the internuclear chronological gradients in the thalamus.

Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational days 13 and 14 (E13 + 14) until the day before birth (E21 + 22). With this progressively delayed comprehensive labelling procedure we determined the time of origin of neurons in the nuclei of the epithalamus, thalamus, and ventral thalamus. The zona incerta, subthalamic nucleus, reticular nucleus, posterior nucleus, and ventral lateral geniculate nucleus are composed of the earliest arising neurons (E13, or before, to E15). The neurons of the lateral habenular nucleus are produced between days E13--16. The neurons of the medial geniculate and lateral geniculate nuclei, the ventrobasal and ventrolateral complexes, and the nucleus lateralis, pars posterior, arise rapidly on days E14--15; the medial geniculate nucleus with a peak on day E14, the others with a peak on day E15. Neurons of a group of nuclei, with ill-defined boundaries medial to the sensory relax nuclei, arise apparently on days E15--16, with a peak on day E15; these may represent the intralaminar nuclei. The next group is generated on days E15--16 but with peak formation time on day E16; this includes the anteroventral, anterodorsal, anteromedial and mediodorsal nuclei. The rhomboid, reuniens and paratenial nuclei, and the paraventricular nucleus, pars anterior, arise next (E16--17). The medial habenular nucleus forms last and over a protracted period (E15--19). With their lengthy generation time the lateral and medial habenular nuclei resemble more the nuclei of the hypothalamus than the nuclei of the dorsal thalamus.     

Double retrograde tracer study of the thalamostriatal projections to the cat caudate nucleus

The distribution of thalamostriatal neurons projecting to the cat caudate nucleus was examined by retrograde fluorescent tracers. Thus, Fast Blue and Diamidino Yellow were concomitantly injected in different rostrocaudal, dorsoventral, or mediolateral sectors of the caudate nucleus. The main findings of this study are as follows: (1) few double-labeled cells were found after two injections in different sectors of the caudate nucleus; (2) double-labeled neurons were more abundant after adjacent injections and they were mainly located in the caudal intralaminar nuclei, in the rhomboid nucleus and in the dorsal mediodorsal nucleus; and (3) there were variations in the spatial organization of the thalamostriatal neurons projecting to various sectors of the caudate nucleus in the different thalamic nuclei known to project to this part of the striatum.     

Development of the diencephalon in the rat. VI. Re-evaluation of the embryonic development of the thalamus on the basis of thymidine-radiographic datings.

The development of the thalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The differentiating, radioresistant neurons of the lateral habenular nucleus, derived from a portion of the superior neuroepithelial lobule (SL1), were settling by day E15 and by this time the habenulopeduncular tract was forming. The neurons of the reticular nucleus, derived from the middle neuroepithelial lobe, began to settle on day E15 but a massive migration was still evident on day E16. Adjacent to the reticular nucleus the internal capsule appeared on day E16; this fiber bundle seemed to be continuous with fibers embedded in the first transitory zone of cells issuing from the dorsal neuroepithelial lobe. Because of the immaturity of the neocortex at this time, it was postulated that thalamocortical fibers of the dorsal thalamus are the earliest components of the internal capsule. By day E17 all the sensory relay nuclei of the thalamus were recognizable and it was assumed that the second transitory zone issuing from the receding dorsal neuroepithelial lobe contained the neurons of the later forming intralaminar nuclei. Suggestive evidence was obtained that the late arising neurons of the medial thalamus (the anterior nuclei, the mediodorsal nucleus, and some or all of the midline nuclei) originate in a portion of the superior neuroepithelial lobule designated as SL2. Our present and previous studies showed that the major divisions of the hypothalamus and thalamus are derived embryonically from distinguishable parts of the third ventricle neuroepithelium. This implies the te third ventricle neuroepithelium has a "mosaic" organization and suggests that the fate of hypothalamic and thalamic neurons may be determined to some extent while their precursors are still proliferating.     

Development of the brain stem in the rat. IV. Thymidine-radiographic study of the time of orgin of neurons in the pontine region

Groups of pregnant rats ware injected with two successive daily doses of ³H-thymidine form gestational day 12 and 13 (E12 + 13) until the day before parturition (E21 + 22) in order to label in their embryos the proliferating precursors of neurons. At 60 days of age the proportion of neurons generated (or no longer labeled) on specific embryonic days was determined quantitatively in 14 nuclei of the pontine region. Peak production time of neurons of the trigeminal mesencephalic nucleus was on day E11 or earlier, with a small proportion generated on day E12. Peak production time of the trigeminal motor neurons was on day E12, with a small proportion produced earlier. Neurons of the principal sensory nucleus were generated between days E13 and E16, with a peak on day E14; the late-produced neurons tended to belong to a class of intermediate and large cells. The bulk of the neurons of the supratrigeminal and infratrigeminal nuclei arose on day E15 and E16. Neurons of the locus coeruleus are produced mostly on day E12, with about 20% of the cells arising on day E13. The bulk of the neurons of the dorsal tegmental nucleus (Gudden's) are produced between days E13 and E15, whereas most of the neurons of the deep (ventral) tegmental nucleus are produced on day E15. A dorsal-to-caudal gradient was also obtained between the dorsal and vental nuclei of the lateral lemniscus, the neurons of the former being generated between days E12 and E15; the latter, between days E13 and E17. The neurons of both the pars lateralis and the pars medialis of the parabrachial nucleus were produced simultaneously between days E13 and E15, with a peak on day E13. the heterogeneous collection of neurons of the pontine paramedial reticular formation was produced from day E11 (or earlier) until day E15. Finally, the neurons of the raphe pontis parvicellularis were generated at an even rate between days E13 and E15, whereas the bulk of the neurons of the raphe pontis magnocellularis were produced on days E15 and E16. On the basis of datings obtained for 9 subdivisions of the entire brain stem trigeminal complex, hypotheses were offered of the cytogenetic components of the system. The sequence of neuron production in the dorsal and deep tegmental nuclei was related to their connections with divisions of the mammillary and habenular nuclei on a “first come-first serve” basis.     

Immunohistochemistry of aromatic L-amino acid decarboxylase in the cat forebrain

The topographic distribution of aromatic L-amino acid decarboxylase (AADC)-immunoreactive (IR) neurons was investigated in the cat hypothalamus, limbic areas, and thalamus by using specific antiserum raised against porcine kidney AADC. The perikarya and main axons were mapped on an atlas in ten cross-sectional drawings from A8 to A16 of the Horsley Clarke stereotaxic plane. AADC-IR neurons were widely distributed in the anterior brain. They were identified in the posterior hypothalamic area, rostral arcuate nucleus of the hypothalamus, dorsal hypothalamic area, and periventricular complex of the hypothalamus, which contain tyrosine hydroxylase (TH)-IR cells and are known as A11 to A14 dopaminergic cell groups. AADC-IR perikarya were also found in the other hypothalamic areas where few or no TH-IR cells have been reported: the supramamillary nucleus, tuberomamillary nucleus, pre- and anterior mamillary nuclei, caudal arcuate nucleus, dorsal hypothalamic area immediately ventral to the mamillothalamic tract, anterior hypothalamic area, area of the tuber cinereum, retrochiasmatic area, preoptic area, suprachiasmatic and dorsal chiasmatic nuclei. We also identified them in the anterior commissure nucleus, bed nucleus of the stria terminalis, stria terminalis, medial and central amygdaloid nuclei, lateral septal nucleus, and nucleus of the diagonal band of Broca. AADC-IR neurons were localized in the ventromedial part of the thalamus, lateral posterior complex, paracentral nucleus and lateral dorsal nucleus of the thalamus, medial habenula, parafascicular nucleus, subparafascicular nucleus, and periaqueductal gray. Conversely, we detected only a few AADC-IR cells in the supraoptic nucleus whose rostral portion contains TH-IR perikarya. Comments are made on the relative localizations of the AADC-IR and TH-IR neurons, on species differences between the cat and rat, as well as on the possible physiological functions of the enzyme AADC.     

Distribution of the VIP-like immunoreactive neurons in the cat central nervous system

Immunohistochemical topographic localization of the vasoactive intestinal polypeptide (VIP)-like immunoreactive neurons in the cat brain was investigated using a peroxidase anti-peroxidase technique. VIP-like immunoreactive neurons were mainly localized in the cerebral cortex, limbic cortex, hypothalamic nuclei; suprachiasmatic nucleus, supraoptic nucleus, paraventricular nucleus, periventricular nucleus and arcuate nucleus, and in the midbrain; such as the central grey and the raphe nucleus. It was demonstrated that VIP-like immunoreactive neurons were widely distributed in the cat brain, particularly in the hypothalamus, compared with those of the rat and mouse; though whether these differences were species-related or due to differences in the physiological conditions remains to be determined. This is the first report of VIP neuronal perikarya in the arcuate nucleus of mammalian species, although these cells are present in the arcuate nucleus of birds.     

Distribution pattern of cell bodies and fibers with neurotensin-like immunoreactivity in the cat hypothalamus

Neurotensin is widely distributed in the central and peripheral nervous systems. Extensive radioimmunoassay and immunohistochemical studies in rats show that the neurotensin immunoreactive perikarya and fibers are most prominent in the hypothalamus. Radioimmunoassay studies have suggested that the levels of neurotensin in the hypothalamus of cats may be six times higher than that of rats. We studied the distribution pattern of neurotensin immunoreactivity within the hypothalamus of the cat by avidin-biotin modification immunohistochemical methods: (1) to define its distribution pattern within the hypothalamus, and (2) to compare our findings with the patterns that have been described in rats. Results show that neurotensin immunoreactive cell bodies and fibers are most prominent in the rostral and intermediate regions of the cat hypothalamus. Cell bodies with neurotensin-like immunoreactivity are seen maximally in the medial preoptic region, the infundibular nucleus, and the lateral hypothalamus. The neurotensin positive fibers are dense in the periventricular regions of the entire rostro-caudal extent of the hypothalamus. This pattern of distribution of neurotensin immunoreactivity is similar to that described in rats. The suprachiasmatic nuclei of the cat hypothalamus, however, contained a significant number of neurotensin immunoreactive cell bodies, an observation not noted in the rat hypothalamus. The neurotensin immunoreactive neurons were more numerous in the lateral hypothalamus than has been reported in rats, but the paraventricular nucleus of the hypothalamus in cats contained fewer neurotensin immunoreactive perikarya. The presence of neurotensin immunoreactive perikarya in the suprachiasmatic nucleus and the apparent increase in the number of neurotensin immunoreactive neurons in the lateral hypothalamus may account for the increased levels of neurotensin reported in cats. Neurotensin has been speculated to play a role in nociception, thermoregulation, and control of arterial pressure by acting as a hormone or a neurotransmitter. Details of the pattern of colocalization of neurotensin with that of other neuropeptides and neurotransmitters will aid in our understanding of its role in these functions.     

Development of the diencephalon in the rat. II. Correlation of the embryonic development of the hypothalamus with the time of origin of its neurons

The development of the nuclei of the hypothalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The diencephalic neuroepithelium was subdivided into three lobes (dorsal, medial, and ventral) and two lobules (superior and inferior). The hypothalamus is derived from the ventral lobe and the inferior lobule. The ventral neuropithelial lobe generates the neurons of most of the early arising hypothalamic structures, including those of the lateral tier nuclei associated with the medial forebrain bundle, and the heterogeneous intermediate tier nuclei. A specialized neuroepithelial region lining the diamond shaped ventricle produces the early neurohypophysial magnocellular neurons; the neurons of the paraventricular nucleus remain at the site, whereas the neurons of the supraoptic nucleus could be traced migrating laterally. The neurons of the late arising hypophysiotropic area of the posterior hypothalamus are derived from components of the inferior neuroepithelial lobule: the dorsomedial and ventromedial nuclei apparently from a shared matrix in the main portion of the inferior lobule; the tuberomammillary-arcuate complex from its posteroventral recess. The triple-decked and sequentially produced components of the mammillary system may arise from separate neuroepithelial sites. The autoradiographic results of the previous study (Altman and Bayer, '78a) showed that the structural and functional heterogeneity of the mature hypothalamus is paralleled by cytogenetic heterochronicity; the present embryonic observations indicate that many of the distinguishable components of the hypothalamus arise from a mosaic of heterogeneous neuroepithelial sites.     

Neurogenesis of basal forebrain cholinergic neurons in rat

The basal forebrain cholinergic system embodies a heterogeneous group of neurons distributed in the basal telencephalon that project topographically to the cortical mantle. We sought to examine the generation of these neurons to determine whether basal forebrain neurons have unique patterns of neurogenesis or, if, in contrast, they are born along general neurogenic gradients. The techniques of tritiated thymidine autoradiography and choline acetyltransferase (ChAT) immunocytochemistry were combined to determine the birthdays and neurogenic gradients of cholinergic cells in this region of rat brain. Cholinergic neurogenesis throughout the basal forebrain ranged from embryonic days 12 to 17 (E12-17). Neurogenesis in the nucleus basalis magnocellularis occurred over E12-16, with a peak day of generation on E13. The horizontal limb nucleus of the diagonal band which is located rostral to the nucleus basalis was generated over E12-17, with the majority of cells arising on E14-15. The rostral-most nuclei of the basal forebrain cholinergic system, the vertical limb of the diagonal band and the medial septum, were generated between E13-17, with peak days of neurogenesis on E15 and E15-16, respectively. These results were evaluated quantitatively and demonstrated that the basal forebrain cholinergic neurons were generated along the general caudal-to-rostral gradient previously described for all neurons in this brain region. The results of this study, in combination with those of similar investigations, emphasize that position-dependent epigenetic factors appear to be more potent determinants of the time of neuronal origin than factors which influence a cell's transmitter phenotype.     

Genesis of morphologically identified neurons in the dorsal lateral geniculate nucleus of the cat

Neurons in the dorsal lateral geniculate nucleus of the cat can be grouped into five morphological classes based on a variety of structural characteristics. These same structural characteristics can serve as morphological signatures for the three physiological classes (X, Y, W) of neurons found in this nucleus. The purpose of this study was to determine if a relationship exists between the birthdate of neurons within the dorsal lateral geniculate nucleus and the adult morphology of those neurons. Seven cats, each of which had received a single injection of 3H-thymidine, were studied. A total of 2,138 Golgi-impregnated neurons were identified in the dorsal lateral geniculate nuclei of these seven cats; 1,517 of these neurons were successfully resectioned and recovered, of which 385 (25%) were found to contain the 3H label. Neurons from each of the five morphological classes were labeled in each of the six animals that received a 3H-thymidine injection between embryonic day 24 (E24) and E28. Class 3 and class 5 neurons were labeled in a cat injected with 3H-thymidine on E30. These findings demonstrate that the development of the morphological class of a neuron in the dorsal lateral geniculate nucleus is independent of the time of its final cell division. Further, given the relationship that exists in the cat's dorsal lateral geniculate nucleus between neuronal structure and function, the present findings suggest that the different physiological classes of cells found in this nucleus undergo their final cell divisions throughout most of the period of neurogenesis except that the functional role of neurons born late in this period may be more restricted.     

Neurogenesis of the amygdaloid nuclear complex in the rhesus monkey.

The time course of neurogenesis for neurons which comprise the amygdaloid complex in Rhesus monkeys was determined using tritiated thymidine autoradiography. Fourteen pregnant monkeys received injections of tritiated thymidine between embryonic days 27 (E27) and 56 of their 165 day gestation and offspring were sacrificed during the early postnatal period. The first neurons destined for the amygdaloid complex were generated at E33 making them among the earliest postmitotic neurons in the telencephalon. Neurogenesis peaked within all nuclei of the amygdaloid complex between E38 and E48 and had ceased between E50 and E56. While amygdaloid neurogenesis in postnatally sacrificed monkeys displayed a dorsal-to-ventral gradient of radiolabeled neurons, the considerable rotation of the temporal lobe during the latter stages of primate development indicates that neurogenesis in the embryo, during the first third of gestation, actually occurs across a medial-to-lateral gradient. This medial-to-lateral gradient occurs as a smooth wave across the amygdaloid nuclei and does not respect neuroanatomical subdivisions or patterns of connectivity of the amygdaloid nuclei in the Rhesus monkey.