The early development of thalamocortical and corticothalamic projections in the mouse

The initial ingrowth of corticothalamic and thalamocortical projections was examined in mice at embryonic and perinatal stages. Fibers, in fixed brains, were labeled with the carbocyanine dye 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindocarbocianine perchlorate (DiI). By E13, the corticofugal fibers had entered the lowest intermediate zone through which they ran, turned over the corpus striatum, and left the cortex. The fibers were arranged in scattered bundles throughout the corpus striatum. At E14 corticofugal axons reached the internal capsule and at E14.5–E15 they established contact within the thalamus. Meanwhile, the thalamocortical afferents reached the neocortex at E13. At this time fibers ran tangentially within the intermediate zone, immediately underneath the cortical plate. By E14, the fibers had started to invade the subplate and, by E15, thalamocortical fibers had begun their radial growth into the cortex. Such radial growth proceeded steadily, invading each cortical layer as it differentiated cytoarchitectonically from the dense cortical plate. The first retrogradely labeled cells were detected at the cortical plate at E15. By the day of birth (E20), thalamocortical fibers had formed a dense branching system within layers VI and V. Our observations indicate that, in mice, the thalamic axons reach the cortex before corticothalamic projections enter the thalamic nuclei. Moreover, the results suggest that the pathway followed by each fiber system is different. By DiI injections into the internal capsule we have also determined that subplate cells are the first to send axons to the thalamus. Accepted: 11 August 1999     

Delta opioid receptor mRNA expression is changed in the thalamus and brainstem of monoarthritic rats

Changes in the mRNA expression of neurotransmitters receptors under chronic pain conditions have been described in various areas of the central nervous system (CNS). Delta opioid receptors (DORs) have been implicated in pain mechanisms but, although its mRNA expression has been studied in the rat CNS, there are no reports describing its distribution in specific thalamic and brainstem nuclei during chronic inflammatory pain. Here, in situ hybridization for DOR mRNA was performed in brain sections from control and monoarthritic (MA) rats with 2, 4, 7 and 14 days of inflammation. Grain densities were determined bilaterally in the ventrobasal complex (VB), posterior (Po), centromedial/centrolateral (CM/CL) and reticular (Rt) nuclei of the thalamus, and in the dorsal reticular (DRt), lateral reticular (LRt) and parvocellular reticular (PCRt) nuclei of the brainstem. Control animals exhibited weak mRNA expression in the VB, Po and CM/CL, as well as in PCRt, while moderate grain densities were observed in the Rt, DRt and LRt. During MA, DOR mRNA expression was significantly decreased (22%) in the Rt contralateral to the affected joint at both 7 and 14 days of inflammation, as compared to controls. A bilateral reduction (35%) was also observed in the DRt at 14 days of MA, while a contralateral increase was found in the PCRt at 7 days (+39%). No significant changes were observed in the other regions analyzed. Thus, data show changes in the DOR mRNA expression during the development of chronic inflammatory pain, in thalamic and brainstem nuclei implicated in pain processing mechanisms.     

Cholinergic stimulation of the nucleus basalis of Meynert and reticular thalamic nucleus affects spike-and-wave discharges in WAG/Rij rats

The role of the cholinergic innervated nucleus basalis of Meynert (NB) and reticular thalamic nucleus (RT) in the generation or modulation of spontaneously occurring spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat model of absence epilepsy. The cholinergic agonist carbachol and the muscarinic antagonist scopolamine were injected in the NB and RT in the doses of 0.55 and 5.5 nmol while the EEG was recorded. Carbachol injected in the NB decreased the number and the mean duration of SWDs. Scopolamine alone had no influence on SWDs, but could antagonize the effects of carbachol if administered simultaneously in NB. Injections of carbachol in the RT inhibited the occurrence of SWDs, but did not affect the mean duration. Scopolamine administered in the RT had no influence on seizure activity. It is concluded that cholinergic stimulation of the NB or the RT inhibits the cortical synchronous activity characterizing SWDs.     

Effects of age and gender on Sirt 1 mRNA expressions in the hypothalamus of the mouse

Sirt1 is a NAD-dependent deacetylase that has been shown as a link between energy metabolism and aging. Its putative role as a target for neurodegenerative disorders has recently been suggested; yet, little is known about the changes that occur in Sirt1 levels in the aging brain. Here we show by in situ hybridization that Sirt1 expression is modified in specific areas of the brain in mice upon aging, and that gender also impacts on this regulation. Mice aged 12 and 24 months had a lower Sirt1 expression specifically in the antero ventral thalamic nucleus (AV) and in the arcuate nucleus (ARC) than their young (4 mo) counterparts, whereas changes were either not noticeable or not significantly modulated in other parts of the brain. Regulation of Sirt1 mRNA levels in the subfornical organ (SFO) and in the substancia nigra part compacta (SNC) depended on gender. These findings suggest that reduced Sirt1 levels upon aging could contribute to a lower Sirt1 activity, and that specific nuclei might be particularly affected.     

Opposite effects of monosodium glutamate on the dopaminergic and GABAergic innervations of the median eminence and the intermediate lobe in the mouse

In the mouse, monosodium glutamate (MSG) administered neonatally provokes the necrosis of most dopaminergic perikarya in the arcuate nucleus, as classically described, but also stimulates surviving neurons as shown by their increase in both size and immunoreactivity for tyrosine hydroxylase (TH). In the treated animals, TH-immunoreactive axons rarefy in the median eminence (ME) external zone, but postnatal dopaminergic innervation of the intermediate lobe (IL) normally develops and even, due to enlarged axonal varicosities, is more conspicuous than in the control littermate IL at same stages. gamma-Aminobutyric acid-ergic (GABAergic) projections in the ME and the IL, revealed with a glutamic acid decarboxylase antiserum, have the same distribution as TH-immunoreactive axons and present the same modifications in the MSG-treated animals. No clearcut differences in dopaminergic and GABAergic innervation patterns can be observed in the IL in treated and control adult mice.     

Differential expression of N-CAM, vimentin and MAP1B during initial pathfinding of olfactory receptor neurons in the mouse embryo

Olfactory receptor neurons extend their primary axons from the nasal epithelium to the olfactory bulb primordium via the frontonasal mesenchyme. In the present study, expression of neuronal markers (vimentin and MAP1B) and N-CAM was immunohistochemically investigated in the development of the olfactory system in mouse embryos. Expression of vimentin and MAP1B was first observed at early day 10 of gestation (D10) in the posterosuperior region of the medial nasal epithelium, while N-CAM was initially detected in the mesenchyme adjacent to the vimentin- and MAP1B-positive nasal epithelium. As development proceeded, the N-CAM positive region in the nasal mesenchyme became broader and reached the olfactory bulb primordium late on day 10. In comparision with adjacent sections, the localization of neuronal marker-positive cells was mostly included in the N-CAM positive region. In addition, we adopted in situ labelling with vital dye (DiI) to directly determine the localization of the olfactory nerve and N-CAM on the same sections. We demonstrated that most extending axons were located in the N-CAM positive region. These results suggest that the expression of N-CAM plays a crucial role in the initial pathfinding of the olfactory nerve.     

Distribution of the largest neuron in mouse caudate-putamen nucleus: Its position in large-cell — Medium-cell clusters

Summary The position of the largest striatal neuron within territories delimited by medium-sized clustered neurons was charted in Nissl-stained sections through the mouse caudate-putamen nucleus. Medium-sized neuron somata occur in close proximity to this large cell at some point in the anteroposterior, mediolateral or dorsoventral extent of its soma. The size of the network of medium-sized neurons associated with the large cell may vary from two to 15 neurons. Even when this network is extensive, the large neuron is never completely surrounded. Most often, this cell also borders a fascicle of internal capsule fibers, and the entire cellular island may be aligned either parallel to or perpendicular to the orientation of these fibers. These findings suggest the hypothesis that cellular territories in the caudate-putamen nucleus have a very specific orientation in three dimensional space.     

The prefrontral cortex of the cat: Anatomical subdivisions based on retrograde labeling of cells in the mediodorsal thalamic nucleus

Different areas of the frontal cortex of the cat were injected with small amounts of horseradish peroxidase. The region of labeled cells in the mediodorsal nucleus of the thalamus (MD) were related to the injected areas. Distinct relations between subdivisions of MD and of the prefrontal cortex were established: a rather large central sector of MD projects to the gyrus proreus and the anterior parts of the gyri sigmoideus, rectus, and frontalis. A narrow lateral band of anterior MD neurons projects predominantly to an area on both sides of the sulcus praesylvius, whereas a postero-lateral band sends fibers to a region on the ventral anterior sylvian gyrus. The area between the presylvian sulcus and the sylvian gyrus is apparently free of MD afferents, but not of other thalamic afferents. A fourth sector of MD, situated dorsomedially, projects to the middle parts of the gyri rectus and frontalis. And a fifth sector, located ventrally to the dorsomedial MD sector, projects to the ventral part of the gyrus rectus. The established subfields of MD and of the prefrontal cortex are discussed with respect to previous anatomical research in the cat.     

Projections from the entorhinal cortex,perirhinal cortex,presubiculum, and parasubiculum to the medial thalamus in macaque monkeys: identifying different pathways using disconnection techniques

The projections from the perirhinal cortex, entorhinal cortex, parasubiculum, and presubiculum to the thalamus were examined using both anterograde and retrograde tracers. Attention focused on the routes taken by these projections, which were delineated by combining surgical tract section with the placement of a tracer. Projections to the anterior thalamic nuclei almost exclusively used the fornix. These relatively light projections, which arose from all areas of the entorhinal cortex, from the presubiculum, parasubiculum, and area 35 of the perirhinal cortex, terminated mainly in the anterior ventral nucleus. In contrast, the projections to the lateral dorsal nucleus from the entorhinal cortex, presubiculum and parasubiculum were denser than those to the anterior thalamic nuclei. The projections to the lateral dorsal nucleus used two routes. While nearly all of the projections from the subicular complex used the fornix, many of the entorhinal cortex projections passed caudally in the temporopulvinar bundle to reach the lateral dorsal nucleus. The perirhinal cortex, as well as the entorhinal cortex, also projects to nucleus medialis dorsalis. These projections exclusively used the external capsule and thence the inferior thalamic peduncle. Other temporal-thalamic projections included those to the medial pulvinar, via the temporopulvinar bundle, from the perirhinal and entorhinal cortices, and those to the paraventricular nucleus from the entorhinal cortex. By identifying these routes, it is possible to appreciate how different lesions might disconnect temporal–diencephalic pathways and so contribute to memory disorders.     

Effects of bilateral microinjections of ibotenic acid in the thalamic reticular nucleus on delta oscillations and sleep in freely-moving rats

The thalamic reticular nucleus (NRT) consists of a large pool of GABAergic neurons located on each side on the anterior, lateral, and ventral surfaces of the dorsal thalamus. The NRT is divided up into sectors. The aim of this study was to investigate the effects of bilateral lesions of the NRT on sleep and sleep oscillations. Only the results concerning delta oscillations will be reported here. As a first step we produced stereotaxically placed electrolytic lesions. The rats presented continuous circling behavior with electroencephalographic (EEG) theta and delta activity and subsequent sudden death. To avoid disruption of the bundles of fibers that pass through the NRT to and from the cerebral cortex, we used the excitotoxic ibotenic acid. Given its high toxicity, we concentrated on the rostral pole of the NRT, which is believed to have powerful effects on the synchronization of oscillatory activity during sleep. Immediately after surgery, the rats fell into a deep sleep during which there was an increase in EEG slow-wave activity and no spindles. On postoperative day 2, corresponding to the destruction period, the sleep/wake cycle partially recovered, but NREM sleep was quantitatively diminished and showed abnormalities (increased latency to sleep onset, sleep fragmentation, gradual elimination of the delta rhythm). It is concluded that the rostral pole of the NRT contributes to normal and pathological EEG synchronization and the organization of sleep in rats.     

Spontaneous phasic activity in the brain: differences between waves in lateral geniculate and central lateral nuclei across sleep states

SUMMARY  Ponto-geniculo-occipital (PGO) waves are spontaneously-occurring macropotential waveforms recorded in the pons, lateral geniculate body (LGB) and occipital cortex. PGO waves mark the onset and course of rapid eye movement sleep (REM). PGO-like waves can be recorded in several brain areas including the thalamic central lateral nucleus (CL). Alerting stimuli elicit PGO waves (PGO_E) from LGB and waves from CL (CL_E) in all behavioural states. We compared spontaneous activity in LGB and CL across behavioral states to examine the relationship of CL waves to PGO waves. Spontaneous waves in LGB and CL may occur concurrently or separately in all states. Although REM is marked by a high level of LGB PGO activity, CL waves are rare. Frequencies of CL and LGB waves are similar in non-REM (NREM) although the waves do not necessarily occur at the same time. These findings suggest that the widespread phasic activity recorded throughout the brain in sleep cannot be assumed to be a non-specific unitary phenomenon propagated from a single brainstem generator.     

Frequency-to-voltage conversion in the pyramidal tract neuron: an important role of the inhibitory postsynaptic potential

Frequency-coded impulses are known to be converted into postsynaptic potentials (PSPs) at the synapse of a target neuron. This can be termed frequency-voltage (F-V) conversion. Studies on this problem in pyramidal tract neurons (PTNs) showed that not only the amplitude but also the duration of depolarizing PSPs was determined as a function of the input impulse frequency. Two opposite patterns of F-V conversion were observed following activation of two input systems to PTNs. Inhibitory postsynaptic potentials were found to play an important role in the regulation of the duration of PSPs by curtailing excitatory post-synaptic potentials.     

Supraoptic neurons in the rat hypothalamo-neurohypophysial explant: double-labeling with Lucifer Yellow injection and immunocytochemical identification of vasopressin- and neurophysin-containing neuroendocrine cells

By combining intracellular electrophysiology with double-labeled intracellular dye-marking and immunocytochemical identification of the same magnocellular neuroendocrine cell, we studied supraoptic neurons in the rat hypothalamo-neurohypophysial explant in vitro. This report examines neurophysiological and light microscopical features of vasopressin- and neurophysin-immunoreactive, pituitary-projecting supraoptic neurons.     

Subfornical organ and hypothalamic paraventricular nucleus connections with median preoptic nucleus neurons: an electrophysiological study in the rat

Summary The role of pathways from the subfornical organ (SFO) to the hypothalamic paraventricular nucleus (PVN) through the median preoptic nucleus (MnPO) in regulating the activity of putative vasopressin (VP)-secreting neurons in the PVN was examined in urethane-anesthetized male rats. The activity of the majority (79%) of SFO neurons antidromically identified as projecting to the MnPO was excited by microiontophoretically (MIPh) applied angiotensin II (ANG II) and the effect was blocked by MIPh-applied saralasin (Sar), an ANG II antagonist. Identified SFO neurons that were excited by MIPh-applied ANG II were also excited by intravenously administered ANG II. Electrical stimulation of the SFO produced orthodromic excitation (48%) or inhibition (24%) of the activity of MnPO neurons antidromically identified as projecting to the PVN. Identified MnPO neurons that were excited by SFO stimulation were also excited by MIPh-applied ANG II, while the remaining neurons were not affected. The excitatory responses to SFO stimulation and to MIPh-applied ANG II were both blocked by MIPh-applied Sar, whereas the inhibitory responses to SFO stimulation were not affected. ANG II injected into the region of the SFO produced either an excitation (55%) or no effect (45%) on the activity of identified MnPO neurons. Electrical stimulation of the MnPO produced orthodromic excitation (27%) or inhibition (23%) of the activity of putative VP-secreting PVN neurons. ANG II injected into the region of the MnPO produced either an excitation (31%) or no effect (69%) on the activity of putative VP-secreting PVN neurons. These observations reveal some possible interconnections between three brain regions and suggest that circulating ANG II excites a population of neurons projecting from the SFO to the MnPO, and that these neurons themselves release ANG II as an excitatory transmitter on part of MnPO neurons projecting to the PVN, thereby causing enhanced activity of putative VP-secreting PVN neurons.     

猫丘脑腹后内侧核内三叉丘系纤维终末的超微结构及其突触联系

本文采用顺行溃变法对猫丘脑腹后内侧核内发自三叉神经尾侧脊束核的三叉丘系纤维终末的超微结构及其突触联系进行了研究。在电灼损毁三叉神经尾侧脊束核四天后 ,在电镜下发现丘脑腹后内侧核内的三叉丘系终末存在三种溃变形式 ,即 :电子致密型溃变 ,电子透明型溃变及神经微丝型溃变 ,以电子致密型溃变终末最为常见。溃变的三叉丘系终末常较大 ,含有大量密集的圆形无颗粒小泡 ,在丘脑腹后内侧核内主要形成不对称型轴—树突触 ,多数溃变轴终末还参与形成以树突为中心的汇聚型突触复合体     

丘脑室旁核形态和功能研究进展

丘脑室旁核（PVT）为丘脑中线核团的重要组成部分,是多种行为的中继传导核团及整合中心,参与动物觉醒、摄食、成瘾、奖赏、恐惧记忆等多种行为的调节。PVT内主要分布着表达囊泡谷氨酸转运体-2（VGluT2）的谷氨酸能兴奋性神经元,却无γ-氨基丁酸（GABA）能抑制性神经元。基于PVT的复杂功能与其内神经元相对单一的兴奋性属性,有必要对PVT内兴奋性神经元进行分类。在本综述中,我们主要对PVT的形态及电生理特点、传入和传出联系、前后两段的形态和功能差异进行总结,并以纤维联系和神经化学性质作为分类标准对PVT的兴奋性神经元进行分类,以便为阐明PVT的复杂功能提供帮助。     

Conditioned and unconditioned forelimb reflex systems in the cat: involvement of the intermediate cerebellum

 Temporary inactivation of the cerebellar interposed nuclei was used to assess the role of the intermediate cerebellum in the performance of forelimb cutaneo-muscular reflexes in the cat. The following types of reflexive responses were evaluated: the classically conditioned and unconditioned forelimb withdrawal responses and the forelimb tactile placing, hopping and magnet responses. The experiments tested the hypothesis that the intermediate cerebellum is involved in the performance of all the above forelimb reflexes. The forelimb withdrawal reflex was classically conditioned in a newly developed paradigm in which animals were first operantly conditioned to stand on four elevated platforms. Trained animals were microinjected with a γ-aminobutyric acid (GABA) agonist, muscimol, in the interposed nuclei, and the effects of inactivation of the intermediate cerebellar output on the forelimb reflexes were examined. The main findings of these experiments are that unilateral muscimol inactivation of the interposed nuclei in the cat abolished the expression of the classically conditioned limb flexion reflex, suppressed the performance of the unconditioned withdrawal reflex and, in parallel, downregulated the tactile placing, hopping and magnet postural responses in the ipsilateral forelimb. These observations are inconsistent with concepts indicating exclusive involvement of the intermediate cerebellum in the classically conditioned reflexes elicited by aversive stimuli. On the contrary, they support the hypothesis of a more global involvement of this structure in learned and unlearned defensive flexion reflexes and in automatic postural response systems. Received: 29 July 1996 / Accepted: 26 September 1996     

Branched output neurons of the rat subthalamic nucleus: electrophysiological study of the synaptic effects on identified cells in the two main target nuclei, the entopeduncular nucleus and the substantia nigra

The synaptic responses of entopeduncular and nigral cells to subthalamic stimulation were studied with extracellular recording techniques in rats with and without chronic lesions. Entopeduncular output cells were identified by antidromic activation from the lateral habenula, ventral anterior thalamic nucleus and tegmenti pedunculopontine nucleus. Nigral cells projecting to superior colliculus were identified by antidromic discharge. Stimulation of the subthalamic nucleus produced a short latency suppression of spontaneous activity (10-60 ms duration) of 89% of the entopeduncular cells tested in chronically lesioned rats. Of these cells, 50% were identified as projecting to lateral habenula. On the other hand, subthalamic nucleus stimulation produced a short latency excitation of 73% of the nigral cells tested (4.16 +/- 0.07 ms). Forty-eight percent of these cells projected to superior colliculus. The subthalamic fibres which terminate in entopeduncular nucleus and substantia nigra, come from the same neuronal population since the majority, if not all, rat subthalamic neurones send branched projections to both these nuclei. Therefore, the two different types of responses recorded in these nuclei are elicited by the activation of a single neuronal population. This dual effect could be easily explained if one of the responses is mediated by local interneurones. If not, the same transmitter induces the two responses. The entopeduncular nucleus and substantia nigra which are the main target nuclei of the subthalamic nucleus, are also the only known outputs of the striatum. The subthalamic efferent cells could thus modulate the activity of the entire striatal descending output. It is noteworthy that this subthalamic control is different in entopeduncular nucleus than in substantia nigra.     

Excitatory input to burst neurons from the labyrinth and its mediating pathway in the cat: location and functional characteristics of burster-driving neurons

Summary 1. Spikes of single neurons were recorded extracellularly in the cat prepositus hypoglossi nucleus and the underlying reticular formation and were identified as type II neurons by horizontal rotation. Among these neurons, those activated by contralateral vestibular nerve stimulation with short latencies (1.5–3.0 ms) were selected for further study. 2. A class of these identified neurons was antidromically activated from the contralateral excitatory burst neuron (EBN) area immediately rostral to the abducens nucleus. Systematic tracking for antidromic stimulation revealed a wide distribution of effective spots in and near the EBN area, with varied latencies and thresholds, suggesting terminal branching in that area. The same neurons were also antidromically activated from the contralateral inhibitory burst neuron (IBN) area, the region near the midline, and the nucleus reticularis tegmenti pontis. 3. These neurons exhibited a characteristic firing pattern related to nystagmus: with contralateral rotation the firing rate gradually increased during the slow phase (type II response) and further steeply increased in a burst fashion before and during the contraversive quick phase. Since the time of occurrence of burst activity in these neurons was similar to that of contralateral ENBs and IBNs that received their axonal projection, it is suggested that they send excitatory input to burst neurons, and can thus be called burster-driving neurons (BDNs). 4. Intracellular study revealed that stimulation of the BDN area produced monosynaptic EPSPs in contralateral EBNs. The monosynaptic connection of BDNs with EBNs was confirmed by detecting unitary extracellular synaptic currents of EBNs with the spike-triggered averaging technique. 5. In contrast to BDNs, another class of nystagmus-related type II neurons in the prepositus hypoglossi and medullary reticular formation showed a discharge pattern similar to that of abducens motoneurons on the same side. None of them was antidromically activated from the contralateral pontine reticular formation including the EBN area. Some neurons responded anti-dromically to stimulation of the ipsilateral dorsomedial pontine reticular formation. 6. In conclusion, the input from the horizontal canal during rotation reaches the contralateral prepositus hypoglossi nucleus and the underlying reticular formation through the vestibular nuclei, and a class of neurons in these structures (BDNs) responds to the canal input in a burst fashion following a tonic type II activity. The axons of BDNs cross the midline and monosynaptically excite EBNs on the side of the canal stimulated. The burst activity of BDNs at the quick phase is suggested to contribute to generation of spike burst of EBNs and IBNs.