Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy.
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Projections to the basilar pontine nuclei (BPN) from a variety of hypothalamic nuclei were traced in the rat utilizing the anterograde transport of biotinylated dextran amine. Light microscopy revealed that the lateral hypothalamic area (LH), the posterior hypothalamic area (PH), and the medial and lateral mammillary nuclei (MMN and LMN) are the four major hypothalamic nuclei that give rise to labeled fibers and terminals reaching the rostral medial and dorsomedial BPN subdivisions. Hypothalamopontine fibers extended caudally through the pontine tegmentum dorsal to the nucleus reticularis tegmenti pontis and then coursed ventrally from the main descending bundle toward the ipsilateral basilar pontine gray. Some hypothalamopontine fibers crossed the midline in the tegmental area just dorsal to the pontine gray to terminate in the contralateral BPN. Electron microscopy revealed that the ultrastructural features of synaptic boutons formed by axons arising in the LH, PH, MMN, and LMN are similar to one another. All labeled hypothalamopontine axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions with dendritic shafts as well as dendritic appendages, and occasionally with neuronal somata. Some labeled boutons formed the central axon terminal in a glomerular synaptic complex. In summary, the present findings indicate that the hypothalamus projects predominantly to the rostral medial and dorsomedial portions of the BPN which, in turn, provide input to the paraflocculus and vermis of the cerebellum. Since the hypothalamic projection zones in the BPN also receive cerebral cortical input, including limbic-related cortex, the hypothalamopontine system might serve to integrate autonomic or limbic-related functions with movement or somatic motor-related activity. Alternatively, since the cerebellum also receives direct input from the hypothalamus, the BPN may function to provide additional somatic and visceral inputs that are used by the cerebellum to perform the integrative function. (+info)
The anterior thalamic head-direction signal is abolished by bilateral but not unilateral lesions of the lateral mammillary nucleus.
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Head-direction (HD) cells are neurons that signal a rat's directional heading in the horizontal plane. Evidence suggests that the lateral mammillary nucleus (LMN) may play an important role in generating the HD signal. Here, we examined the role of LMN in the HD circuit by comparing the effects of unilateral and bilateral LMN lesions on the activity of HD cells in the anterodorsal thalamus (AD). HD cells were recorded from AD in freely behaving rats. In the middle of the recording session, the rat received either bilateral or unilateral lesions of LMN. Immediately after the lesion, we continued recording the same HD cell in AD that had been recorded before the lesion. Additional cells were recorded from lesioned animals for up to 3 weeks after the lesion. We found that bilateral lesions of LMN permanently abolish HD cells in AD. After bilateral lesions, AD exhibits unusual rhythmic oscillations and velocity-correlated spike activity. Unilateral lesions of LMN did not abolish HD cells in AD. After unilateral lesions, the firing properties of HD cells in AD become more similar to those of HD cells in the intact hemisphere of LMN. We discuss the implications of these findings for understanding the role of LMN in the HD circuit. (+info)
Group II selective metabotropic glutamate receptor agonists and local cerebral glucose use in the rat.
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The novel mGluR agonist LY354740 and a related analogue LY379268 are selective for mGluR2/3 receptors and are centrally active after systemic administration. In this study, rates of local cerebral glucose use were measured using the [14C]2-deoxyglucose autoradiographic technique to examine the functional consequences of their systemic administration in the conscious rat. Both LY354740 (0.3, 3.0, 30 mg/kg) and LY379268 (0.1, 1.0, 10 mg/kg) produced dose-dependent changes in glucose use. After LY354740 (3.0mg/kg), 4 of the 42 regions measured showed statistically significant changes from vehicle-treated controls: red nuclei (-16%), mammillary body (-25%), anterior thalamus (-29%), and the superficial layer of the superior colliculus (+50%). An additional 15 regions displayed significant reductions in function-related glucose use (P < .05) in animals treated with LY354740 (30 mg/ kg). LY379268 (0.1, 1.0, 10 mg/kg) produced changes in glucose metabolism in 20% of the brain regions analyzed. Significant increases (P < .05) in glucose use were evident in the following: the superficial layer of the superior colliculus (+81%), locus coeruleus (+57%), genu of the corpus callosum (+31%), cochlear nucleus (+26%), inferior colliculus (+20%), and the molecular layer of the hippocampus (+14%). Three regions displayed significant decreases: mammillary body (-34%), anteroventral thalamic nucleus (-28%), and the lateral habenular nucleus (-24%). These results show the important functional involvement of the limbic system together with the participation of components of different sensory systems in response to the activation of mGluR2 and mGluR3 with LY354740 and LY379268. (+info)
Winged helix transcription factor Foxb1 is essential for access of mammillothalamic axons to the thalamus.
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Our aim was to study the mechanisms of brain histogenesis. As a model, we have used the role of winged helix transcription factor gene Foxb1 in the emergence of a very specific morphological trait of the diencephalon, the mammillary axonal complex. Foxb1 is expressed in a large hypothalamic neuronal group (the mammillary body), which gives origin to a major axonal bundle with branches to thalamus, tectum and tegmentum. We have generated mice carrying a targeted mutation of Foxb1 plus the tau-lacZ reporter. In these mutants, a subpopulation of dorsal thalamic ventricular cells "thalamic palisade" show abnormal persistence of Foxb1 transcriptional activity; the thalamic branch of the mammillary axonal complex is not able to grow past these cells and enter the thalamus. The other two branches of the mammillary axonal complex (to tectum and tegmentum) are unaffected by the mutation. Most of the neurons that originate the mammillothalamic axons suffer apoptosis after navigational failure. Analysis of chimeric brains with wild-type and Foxb1 mutant cells suggests that correct expression of Foxb1 in the thalamic palisade is sufficient to rescue the normal phenotype. Our results indicate that Foxb1 is essential for diencephalic histogenesis and that it exerts its effects by controlling access to the target by one particular axonal branch. (+info)
Modeling attractor deformation in the rodent head-direction system.
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We present a model of the head-direction circuit in the rat that improves on earlier models in several respects. First, it provides an account of some of the unique characteristics of head-direction (HD) cell firing in the lateral mammillary nucleus and the anterior thalamus. Second, the model functions without making physiologically unrealistic assumptions. In particular, it implements attractor dynamics in postsubiculum and lateral mammillary nucleus without directionally tuned inhibitory neurons, which have never been observed in vivo, and it integrates angular velocity without the use of multiplicative synapses. The model allows us to examine the relationships among three HD areas and various properties of their representations. A surprising result is that certain combinations of purported HD cell properties are mutually incompatible, suggesting that the lateral mammillary nucleus may not be the primary source of head direction input to anterior thalamic HD cells. (+info)
Neural correlates for angular head velocity in the rat dorsal tegmental nucleus.
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Many neurons in the rat lateral mammillary nuclei (LMN) fire selectively in relation to the animal's head direction (HD) in the horizontal plane independent of the rat's location or behavior. One hypothesis of how this representation is generated and updated is via subcortical projections from the dorsal tegmental nucleus (DTN). Here we report the type of activity in DTN neurons. The majority of cells (75%) fired as a function of the rat's angular head velocity (AHV). Cells exhibited one of two types of firing patterns: (1) symmetric, in which the firing rate was positively correlated with AHV during head turns in both directions, and (2) asymmetric, in which the firing rate was positively correlated with head turns in one direction and correlated either negatively or not at all in the opposite direction. In addition to modulation by AHV, some of the AHV cells (40.1%) were weakly modulated by the rat's linear velocity, and a smaller number were modulated by HD (11%) or head pitch (15.9%). Autocorrelation analyses indicated that with the head stationary, AHV cells displayed irregular discharge patterns. Because afferents from the DTN are the major source of information projecting to the LMN, these results suggest that AHV information from the DTN plays a significant role in generating the HD signal in LMN. A model is proposed showing how DTN AHV cells can generate and update the LMN HD cell signal. (+info)
Development of selective verbal memory impairment secondary to a left thalamic infarct: a longitudinal case study.
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A 68 year old man suffered an acute dysphasic episode with persistent memory disturbance while taking part as a control in a longitudinal magnetic resonance imaging (MRI) study. A small new left thalamic infarct involving the mamillo-thalamic tract could be demonstrated on volumetric MRI, coinciding with the development of a selective verbal memory impairment. This suggests that lateralisation of cognitive processing of visual and verbal material exists at the thalamic as well as the cortical level. High resolution volumetric MRI may be helpful in demonstrating small subcortical infarcts that may not be seen using computed tomography or conventional MRI. (+info)
Evidence of a spatial encoding deficit in rats with lesions of the mammillary bodies or mammillothalamic tract.
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The present study sought to identify the role of the mammillary bodies and their projections to the anterior thalamic nuclei for spatial memory. Rats with either selective, neurotoxic mammillary body lesions or discrete mammillothalamic tract lesions were tested on various spatial working memory tasks. Tests using the T-maze, radial-arm maze, and water maze were manipulated to compare three possible theories of mammillary body function by increasing proactive interference, increasing retention interval, and taxing the rapid processing of novel spatial stimuli. On T-maze alternation and radial-arm maze tasks, both lesion groups were initially impaired but seemed to recover. Transfer tests revealed, however, a more permanent change in performance, suggesting a failure to use distal (allocentric) cues. Consistent with this, both groups were also impaired at matching-to-place in the water maze and showed little improvement with practice. Nevertheless, once the lesion groups had been trained on a task, they were not affected differentially either by an increase of proactive interference or by retention intervals of up to 30 min. Although both mammillary body and mammillothalamic tract lesions resulted in similar impairments, the mammillothalamic tract group was the more affected when acquiring new spatial information. Together, these results suggest that mammillary body damage causes an encoding deficit when learning new spatial tasks, resulting in a suboptimal mode of performance, which may reflect a loss of directional heading information. (+info)