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Forrest Haun - One of the best experts on this subject based on the ideXlab platform.
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Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus
The Journal of Neuroscience, 1992Co-Authors: T C Eckenrode, Marion Murray, Forrest HaunAbstract:Innervation of specific peptidergic and cholinergic compartments of the interpeduncular nucleus (IPN) was investigated using embryonic cell suspension transplants immunoreactive for substance P (SP) and ChAT. In both neonatal and adult host rats, the IPN was first denervated of its normal SP and cholinergic input from the medial Habenula by bilateral lesions of the fasciculi retroflexi (FR). In adult hosts, transplants of embryonic Habenular cells placed near the denervated IPN mediated a return of the normal pattern of SP staining restricted to Habenula- target subnuclei, plus an increase in staining intensity of SP cells intrinsic to the IPN. There was no recovery of ChAT staining. A similar pattern of SP staining resulted following Habenular transplants into neonatal hosts, but in addition there was a partial recovery of normal ChAT staining in cholinergic subnuclei and anomalous ChAT staining in normally peptidergic subnuclei. Control transplants of embryonic thalamus cells placed into adult hosts produced a surprising pattern of ChAT staining in the IPN identical to that seen with Habenula transplants placed into neonatal hosts; the adult IPN was thus able to support reinnervation mediated by an aberrant cholinergic source while being refractory to its normal Habenular cholinergic afferents. This pattern of results implies regulation by the IPN of Habenular SP and cholinergic innervation, and some interaction between the maturing normal cholinergic afferents and their targets that is missing when these afferent sources are abnormal.
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Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus
The Journal of Neuroscience, 1992Co-Authors: Forrest Haun, T C Eckenrode, Marion MurrayAbstract:The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal Habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in Habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the “flower pot” test, and assayed (1) normal adult rats, (2) FR- lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal Habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (Habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (Habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in Habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Valerie Voon - One of the best experts on this subject based on the ideXlab platform.
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avoiding monetary loss a human Habenula functional mri ultra high field study
Cortex, 2021Co-Authors: Kathrin Weidacker, Seunggoo Kim, Camilla L Nord, Catarina Rua, Christopher T Rodgers, Valerie VoonAbstract:Abstract A number of convergent human neuroimaging and animal studies suggest that Habenula neurons fire in anticipation of non-rewarding outcomes, and suppress their firing in anticipation of rewarding outcomes. This normative function of the Habenula appears disrupted in depression, and may be critical to the anti-depressant effects of ketamine. However, studying Habenula functionality in humans using standard 3 T MRI is inherently limited by its small size. We employed ultra-high field (7 T) fMRI to investigate Habenular activity in eighteen healthy volunteers during a Monetary Incentive Delay Task, focussing on loss avoidance, monetary loss and neutral events. We assessed neural activation in the field of view (FOV) in addition to ROI-based Habenula-specific activity and generalized task-dependent functional connectivity. Whole FOV results indicated substantial neural differences between monetary loss and neutral outcomes, as well as between loss avoidance and neutral outcomes. Habenula-specific analyses showed bilateral deactivation during loss avoidance, compared to other outcomes. This first investigation into the Habenula's role during loss avoidance revealed that the left Habenula further differentiated between loss avoidance and monetary loss. Functional connectivity between the right Habenula and the ipsilateral hippocampus and subcallosal cingulate (regions implicated in memory and depression pathophysiology) was enhanced when anticipating potential losses compared to anticipating neutral outcomes. Our findings suggest that the human Habenula responds most strongly to outcomes of loss avoidance when compared to neutral and monetary losses, suggesting a role for the Habenula in both reward and aversive processing. This has critical relevance to understanding the pathophysiology of Habenula function in mood and other neuropsychiatric disorders, as well as the mechanism of action of Habenula-targeting antidepressants such as ketamine.
Marion Murray - One of the best experts on this subject based on the ideXlab platform.
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Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus
The Journal of Neuroscience, 1992Co-Authors: T C Eckenrode, Marion Murray, Forrest HaunAbstract:Innervation of specific peptidergic and cholinergic compartments of the interpeduncular nucleus (IPN) was investigated using embryonic cell suspension transplants immunoreactive for substance P (SP) and ChAT. In both neonatal and adult host rats, the IPN was first denervated of its normal SP and cholinergic input from the medial Habenula by bilateral lesions of the fasciculi retroflexi (FR). In adult hosts, transplants of embryonic Habenular cells placed near the denervated IPN mediated a return of the normal pattern of SP staining restricted to Habenula- target subnuclei, plus an increase in staining intensity of SP cells intrinsic to the IPN. There was no recovery of ChAT staining. A similar pattern of SP staining resulted following Habenular transplants into neonatal hosts, but in addition there was a partial recovery of normal ChAT staining in cholinergic subnuclei and anomalous ChAT staining in normally peptidergic subnuclei. Control transplants of embryonic thalamus cells placed into adult hosts produced a surprising pattern of ChAT staining in the IPN identical to that seen with Habenula transplants placed into neonatal hosts; the adult IPN was thus able to support reinnervation mediated by an aberrant cholinergic source while being refractory to its normal Habenular cholinergic afferents. This pattern of results implies regulation by the IPN of Habenular SP and cholinergic innervation, and some interaction between the maturing normal cholinergic afferents and their targets that is missing when these afferent sources are abnormal.
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Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus
The Journal of Neuroscience, 1992Co-Authors: Forrest Haun, T C Eckenrode, Marion MurrayAbstract:The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal Habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in Habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the “flower pot” test, and assayed (1) normal adult rats, (2) FR- lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal Habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (Habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (Habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in Habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Robert Turner - One of the best experts on this subject based on the ideXlab platform.
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mapping of the internal structure of human Habenula with ex vivo mri at 7t
Frontiers in Human Neuroscience, 2013Co-Authors: Barbara Strotmann, Arno Villringer, Carsten Kogler, Pierrelouis Bazin, Marcel Weiss, Robert TurnerAbstract:The Habenula is a small but important nucleus located next to the third ventricle in front of the pineal body. It helps to control the human reward system and is considered to play a key role in emotion, showing increased activation in major depressive disorders. Its dysfunction may underlie several neurological and psychiatric disorders. It is now possible to visualize the Habenula and its anatomical subdivisions-medial Habenula (MHB) and lateral Habenula (LHB)-using MR techniques. The aim of this study was to further differentiate substructures within human lateral Habenula (LHB) using ex vivo ultra-high field MR structural imaging, distinguishing between a medial part (m-LHB) and a lateral part (l-LHB). High resolution T1w images with 0.3-mm isotropic resolution and T2(*)w images with 60-micrometer isotropic resolution were acquired on a 7T MR scanner and quantitative maps of T1 and T2(*) were calculated. Cluster analysis of image intensity was performed using the Fuzzy and Noise Tolerant Adaptive Segmentation Method (FANTASM) tool. Ultra-high resolution structural MRI of ex vivo brain tissue at 7T provided sufficient SNR and contrast to discriminate the medial and lateral Habenular nuclei. Heterogeneity was observed in the lateral Habenula (LHB) nuclei, with clear distinctions between lateral and medial parts (m-LHB, l-LHB) and with the neighboring medial Habenula (MHB). Clustering analysis based on the T1 and T2(*) maps strongly showed 4-6 clusters as subcomponents of lateral and medial Habenula.
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isotropic high resolution diffusion imaging of human Habenula in vivo at 7t
International Society for Magnetic Resonance in Medicine 19th Annual Meeting, 2011Co-Authors: Barbara Strotmann, Arno Villringer, Alfred Anwander, Robin M Heidemann, Eugenia Solanocastiella, Robert TurnerAbstract:Introduction: The Habenula (lat. habena meaning rein, Hb) is in control of the human reward system: positive reward is signaled by the dopamine system, whereas disappointment is linked to Habenular activation [1,2]. Overactivation of the lateral Habenula is associated with depression [3,4]. The Habenula is located next to the third ventricle in front of the pineal body and is divided into a medial and lateral part (Fig. 1), which receive input from frontal parts of the brain via the stria medullaris and project down the brainstem via the fasciculus retroflexus [5]. The Habenular commissure connecting the nuclei on both hemispheres forms the Habenular trigone. Visualization of this structure is difficult because of its small size of approximately 5-9 mm in diameter. Its connectivity is poorly understood in vivo. In the present study, we made use of a high magnetic field strength and a combined approach of reduced FOV acquisition (zoomed imaging) and parallel imaging (GRAPPA), given the name ZOOPPA [6]. With this approach, diffusion-weighted (DW) images with 1 mm isotropic resolution can be obtained at 7T. The high spatial and angular resolution of the data enables efficient DW imaging of the human Habenula. Methods: MRI experiments were performed on a 7T whole-body MR scanner (MAGNETOM 7T, Siemens Healthcare, Erlangen, Germany) with a 24-element phased array head coil (Nova Medical, Wilmington, MA, USA). Informed consent was obtained before each study. DW images were acquired with a unipolar Stejskal-Tanner sequence: TR = 10400 ms, TE = 82 ms, FOV =144x150 mm, partial Fourier = 6/8, isotropic resolution 1.0 mm, 71 slices with 10% overlap, DW with b = 1000 s/mm, 60 directions and 4 averages. For the combined approach of zoomed imaging and parallel imaging, outer-volume suppression and GRAPPA was used as described in [6]. A total acceleration factor of 4.2 was used. The total acquisition time was 48 min. The DW images were noise cleaned, corrected for subject motion and co-registered and re-grided to a quantitative T1-weighted anatomical scan, provided by an MP2RAGE sequence with 0.7 mm isotropic resolution. For all DWI acquisitions, fat suppression was obtained using the method proposed by Ivanow et al. [7]. Multiple fibre orientations were computed in each voxel using the ball-and-2-sticks model [8]. Results and Discussion: Figure 2 shows colour-coded main fibre orientations with significant signal contribution (f-value > 0.05) in coronal and axial brain section containing the human Habenula, superimposed on the quantitative high-resolution T1 map and compared with stain sections (Fig. 1) [9,10]. We can identify medial Habenular (MHB) nuclei presenting only one fibre orientation running into the anterior-posterior direction (green), whereas the lateral Habenula (LHB) shows simultaneously a more superiorinferior orientation (blue). The Habenular commissure (HBC) connecting both hemispheres clearly shows a right-left orientation (red). Using probabilistic tractography [8] we can detect stria medullaris and fasciculus retroflexus as two major fibre bundles connecting Habenular nuclei with limbic forebrain structures and brainstem (Fig. 3). Whereas fibres from LHB seem to run mainly to the forebrain, tracts from MHB go down to the brainstem and to its commissure as illustrated by streamline tractography using spherical deconvolution [11] (Fig. 4). Conclusion: The combination of zoomed imaging with parallel imaging – ZOOPPA enables DWI acquisitions with 1 mm isotropic resolution at 7T. The data show distinct nuclei of the human Habenula in vivo. We identified lateral and medial nuclei with their connecting fibre bundles to the forebrain and the brainstem. The nuclei are clearly visible on the quantitative T1 map. with a high myelinisation of the LHB and the HBC. Further study of the Habenular subdivisions and their role in brain function is likely to improve understanding of the pathophysiology of a wide range of neurologic and psychiatric disorders.
Alexander F Schier - One of the best experts on this subject based on the ideXlab platform.
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comprehensive identification and spatial mapping of Habenular neuronal types using single cell rna seq
Current Biology, 2018Co-Authors: Shristi Pandey, Karthik Shekhar, Aviv Regev, Alexander F SchierAbstract:Summary The identification of cell types and marker genes is critical for dissecting neural development and function, but the size and complexity of the brain has hindered the comprehensive discovery of cell types. We combined single-cell RNA-seq (scRNA-seq) with anatomical brain registration to create a comprehensive map of the zebrafish Habenula, a conserved forebrain hub involved in pain processing and learning. Single-cell transcriptomes of ∼13,000 Habenular cells with 4× cellular coverage identified 18 neuronal types and dozens of marker genes. Registration of marker genes onto a reference atlas created a resource for anatomical and functional studies and enabled the mapping of active neurons onto neuronal types following aversive stimuli. Strikingly, despite brain growth and functional maturation, cell types were retained between the larval and adult Habenula. This study provides a gene expression atlas to dissect Habenular development and function and offers a general framework for the comprehensive characterization of other brain regions.