21 results on '"Haber SN"'
Search Results
2. Functional Segmentation of the Anterior Limb of the Internal Capsule: Linking White Matter Abnormalities to Specific Connections.
- Author
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Safadi Z, Grisot G, Jbabdi S, Behrens TE, Heilbronner SR, McLaughlin NCR, Mandeville J, Versace A, Phillips ML, Lehman JF, Yendiki A, and Haber SN
- Subjects
- Adult, Animals, Bipolar Disorder pathology, Brain Mapping, Diffusion Magnetic Resonance Imaging, Female, Humans, Image Processing, Computer-Assisted, Macaca, Male, Internal Capsule anatomy & histology, White Matter anatomy & histology
- Abstract
The anterior limb of the internal capsule (ALIC) carries thalamic and brainstem fibers from prefrontal cortical regions that are associated with different aspects of emotion, motivation, cognition processing, and decision-making. This large fiber bundle is abnormal in several psychiatric illnesses and a major target for deep brain stimulation. Yet, we have very little information about where specific prefrontal fibers travel within the bundle. Using a combination of tracing studies and diffusion MRI in male nonhuman primates, as well as diffusion MRI in male and female human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions within the capsule. Fractional anisotropy (FA) abnormalities in patients with bipolar disorder were detected when FA was averaged in the ALIC segment that carries ventrolateral prefrontal cortical connections. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and demonstrate the utility of applying connectivity profiles of large white matter bundles based on animal anatomic studies to human connections and associating disease abnormalities in those pathways with specific connections. The ability to functionally segment large white matter bundles into their components begins a new era of refining how we think about white matter organization and use that information in understanding abnormalities. SIGNIFICANCE STATEMENT The anterior limb of the internal capsule (ALIC) connects prefrontal cortex with the thalamus and brainstem and is abnormal in psychiatric illnesses. However, we know little about the location of specific prefrontal fibers within the bundle. Using a combination of animal tracing studies and diffusion MRI in animals and human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions. We then demonstrated that differences in FA values between bipolar disorder patients and healthy control subjects were specific to a given segment. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and for refining how we think about white matter organization in general., (Copyright © 2018 the authors 0270-6474/18/382106-12$15.00/0.) more...
- Published
- 2018
- Full Text
- View/download PDF
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3. Combinatorial Inputs to the Ventral Striatum from the Temporal Cortex, Frontal Cortex, and Amygdala: Implications for Segmenting the Striatum.
- Author
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Choi EY, Ding SL, and Haber SN
- Subjects
- Animals, Macaca fascicularis, Macaca mulatta, Macaca nemestrina, Male, Neural Pathways anatomy & histology, Neuroanatomical Tract-Tracing Techniques, Amygdala anatomy & histology, Corpus Striatum anatomy & histology, Frontal Lobe anatomy & histology, Temporal Lobe anatomy & histology
- Abstract
The canonical striatal map, based predominantly on frontal corticostriatal projections, divides the striatum into ventromedial-limbic, central-association, and dorsolateral-motor territories. While this has been a useful heuristic, recent studies indicate that the striatum has a more complex topography when considering converging frontal and nonfrontal inputs from distributed cortical networks. The ventral striatum (VS) in particular is often ascribed a "limbic" role, but it receives diverse information, including motivation and emotion from deep brain structures, cognition from frontal cortex, and polysensory and mnemonic signals from temporal cortex. Using anatomical tract-tracing in 17 male adult monkeys ( Macaca nemestrina , Macaca fascicularis , Macaca mulatta ), we build upon this striatal map by systematically mapping inputs from frontal cortex, amygdala, temporal pole, and medial temporal cortex. We find that the VS contains heterogeneous subregions that become apparent when considering both the identities and strengths of inputs. We parcellated the VS into a ventromedial sector receiving motivation and emotion-related information from regions including area TG, ventromedial PFC, ACC, and amygdala; and a more functionally diverse dorsolateral sector that receives this information coupled to cognitive and sensorimotor information from dorsolateral PFC, ventrolateral PFC, premotor cortex, area TAr, and area TEr. Each sector was further parcellated into smaller regions that had different proportions of these inputs. Together, the striatum contains complex, selective input combinations, providing substrates for myriad associations. This VS parcellation provides a map that can guide and interpret functional interactions in healthy individuals and those with psychiatric disorders, and may be useful in targeting treatments for specific psychiatric conditions. more...
- Published
- 2017
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4. Organization of the Anterior Limb of the Internal Capsule in the Rat.
- Author
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Coizet V, Heilbronner SR, Carcenac C, Mailly P, Lehman JF, Savasta M, David O, Deniau JM, Groenewegen HJ, and Haber SN
- Subjects
- Animals, Male, Rats, Rats, Sprague-Dawley, Species Specificity, Connectome methods, Gyrus Cinguli cytology, Internal Capsule cytology, Prefrontal Cortex cytology
- Abstract
Dysfunction of the orbitofrontal (OFC) and anterior cingulate (ACC) cortices has been linked with several psychiatric disorders, including obsessive-compulsive disorder, major depressive disorder, posttraumatic stress disorder, and addiction. These conditions are also associated with abnormalities in the anterior limb of the internal capsule, the white matter (WM) bundle carrying ascending and descending fibers from the OFC and ACC. Furthermore, deep-brain stimulation (DBS) for psychiatric disorders targets these fibers. Experiments in rats provide essential information on the mechanisms of normal and abnormal brain anatomy, including WM composition and perturbations. However, whereas descending prefrontal cortex (PFC) fibers in primates form a well defined and topographic anterior limb of the internal capsule, the specific locations and organization of these fibers in rats is unknown. We address this gap by analyzing descending fibers from injections of an anterograde tracer in the rat ACC and OFC. Our results show that the descending PFC fibers in the rat form WM fascicles embedded within the striatum. These bundles are arranged topographically and contain projections, not only to the striatum, but also to the thalamus and brainstem. They can therefore be viewed as the rat homolog of the primate anterior limb of the internal capsule. Furthermore, mapping these projections allows us to identify the fibers likely to be affected by experimental manipulations of the striatum and the anterior limb of the internal capsule. These results are therefore essential for translating abnormalities of human WM and effects of DBS to rodent models. SIGNIFICANCE STATEMENT Psychiatric diseases are linked to abnormalities in specific white matter (WM) pathways, and the efficacy of deep-brain stimulation relies upon activation of WM. Experiments in rodents are necessary for studying the mechanisms of brain function. However, the translation of results between primates and rodents is hindered by the fact that the organization of descending WM in rodents is poorly understood. This is especially relevant for the prefrontal cortex, abnormal connectivity of which is central to psychiatric disorders. We address this gap by studying the organization of descending rodent prefrontal pathways. These fibers course through a subcortical structure, the striatum, and share important organization principles with primate WM. These results allow us to model primate WM effectively in the rodent., (Copyright © 2017 the authors 0270-6474/17/372539-16$15.00/0.) more...
- Published
- 2017
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5. Frontal cortical and subcortical projections provide a basis for segmenting the cingulum bundle: implications for neuroimaging and psychiatric disorders.
- Author
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Heilbronner SR and Haber SN
- Subjects
- Animals, Corpus Callosum physiology, Frontal Lobe physiology, Gyrus Cinguli physiology, Macaca fascicularis, Macaca mulatta, Macaca nemestrina, Male, Mental Disorders metabolism, Neural Pathways anatomy & histology, Neural Pathways physiology, Corpus Callosum anatomy & histology, Frontal Lobe anatomy & histology, Gyrus Cinguli anatomy & histology, Mental Disorders pathology, Neuroimaging trends
- Abstract
The cingulum bundle (CB) is one of the brain's major white matter pathways, linking regions associated with executive function, decision-making, and emotion. Neuroimaging has revealed that abnormalities in particular locations within the CB are associated with specific psychiatric disorders, including depression and bipolar disorder. However, the fibers using each portion of the CB remain unknown. In this study, we used anatomical tract-tracing in nonhuman primates (Macaca nemestrina, Macaca fascicularis, Macaca mulatta) to examine the organization of specific cingulate, noncingulate frontal, and subcortical pathways through the CB. The goals were as follows: (1) to determine connections that use the CB, (2) to establish through which parts of the CB these fibers travel, and (3) to relate the CB fiber pathways to the portions of the CB identified in humans as neurosurgical targets for amelioration of psychiatric disorders. Results indicate that cingulate, noncingulate frontal, and subcortical fibers all travel through the CB to reach both cingulate and noncingulate targets. However, many brain regions send projections through only part, not all, of the CB. For example, amygdala fibers are not present in the caudal portion of the dorsal CB. These results allow segmentation of the CB into four unique zones. We identify the specific connections that are abnormal in psychiatric disorders and affected by neurosurgical interventions, such as deep brain stimulation and cingulotomy., (Copyright © 2014 the authors 0270-6474/14/3410041-14$15.00/0.) more...
- Published
- 2014
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6. Estimates of projection overlap and zones of convergence within frontal-striatal circuits.
- Author
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Averbeck BB, Lehman J, Jacobson M, and Haber SN
- Subjects
- Animals, Dextrans, Imaging, Three-Dimensional, Isoquinolines, Macaca mulatta, Male, Rhodamines, Brain Mapping, Corpus Striatum anatomy & histology, Frontal Lobe anatomy & histology, Nerve Net physiology, Neural Pathways physiology
- Abstract
Frontal-striatal circuits underlie important decision processes, and pathology in these circuits is implicated in many psychiatric disorders. Studies have shown a topographic organization of cortical projections into the striatum. However, work has also shown that there is considerable overlap in the striatal projection zones of nearby cortical regions. To characterize this in detail, we quantified the complete striatal projection zones from 34 cortical injection locations in rhesus monkeys. We first fit a statistical model that showed that the projection zone of a cortical injection site could be predicted with considerable accuracy using a cross-validated model estimated on only the other injection sites. We then examined the fraction of overlap in striatal projection zones as a function of distance between cortical injection sites, and found that there was a highly regular relationship. Specifically, nearby cortical locations had as much as 80% overlap, and the amount of overlap decayed exponentially as a function of distance between the cortical injection sites. Finally, we found that some portions of the striatum received inputs from all the prefrontal regions, making these striatal zones candidates as information-processing hubs. Thus, the striatum is a site of convergence that allows integration of information spread across diverse prefrontal cortical areas., (Copyright © 2014 the authors 0270-6474/14/339497-09$15.00/0.) more...
- Published
- 2014
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7. The rat prefrontostriatal system analyzed in 3D: evidence for multiple interacting functional units.
- Author
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Mailly P, Aliane V, Groenewegen HJ, Haber SN, and Deniau JM
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- Animals, Corpus Striatum anatomy & histology, Electroencephalography, Imaging, Three-Dimensional, Male, Phytohemagglutinins metabolism, Prefrontal Cortex anatomy & histology, Rats, Rats, Sprague-Dawley, Brain Mapping, Corpus Striatum physiology, Neural Pathways physiology, Prefrontal Cortex physiology
- Abstract
Previous studies in monkeys disclosed a specific arrangement of corticostriatal projections. Prefrontal and premotor areas form dense projection fields surrounded by diffuse terminal areas extending outside the densely innervated region and overlapping with projections from other areas. In this study, the mode of prefrontostriatal innervation was analyzed in rats using a 3D approach. Following injections of tracers in defined cortical areas, 3D maps from individual cases were elaborated and combined into a global 3D map allowing us to define putative overlaps between projection territories. In addition to providing a detailed 3D mapping of the topographic representation of prefrontal cortical areas in the rat striatum, the results stress important similarities between the rodent and primate prefrontostriatal projections. They share the dual pattern of focal and diffuse corticostriatal projections. Moreover, besides segregated projections consistent with parallel processing, the interweaving of projection territories establishes specific patterns of overlaps spatially organized along the dorsoventral, mediolateral, and anteroposterior striatal axis. In particular, the extensive striatal projection fields from the prelimbic and anterior cingulate areas, which partly overlap the terminal fields from medial, orbital, and lateral prefrontal cortical areas, provide putative domains of convergence for integration between reward, cognitive, and motor processes. more...
- Published
- 2013
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8. The organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: implications for Basal Ganglia models and deep brain stimulation.
- Author
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Haynes WI and Haber SN
- Subjects
- Animals, Fluorescent Dyes metabolism, Imaging, Three-Dimensional, Leucine metabolism, Macaca fascicularis, Macaca nemestrina, Male, Proline metabolism, Tritium metabolism, Brain Mapping, Neural Pathways physiology, Prefrontal Cortex anatomy & histology, Prefrontal Cortex physiology, Subthalamic Nucleus anatomy & histology, Subthalamic Nucleus physiology
- Abstract
The identification of a hyperdirect cortico-subthalamic nucleus connection highlighted the important role of the subthalamic nucleus (STN) in regulating behavior. However, this pathway was shown primarily from motor areas. Hyperdirect pathways associated with cognitive and motivational cortical regions are particularly relevant given recent data from deep brain stimulation, both for neurologic and psychiatric disorders. Our experiments were designed to demonstrate the existence and organization of prefrontal-STN projections, help delineate the "limbic" STN, and determine whether convergence between cortico-STN fibers from functionally diverse cortical areas exists in the STN. We injected anterograde tracers in the ventromedial prefrontal, orbitofrontal, anterior cingulate, and dorsal prefrontal cortices of Macaca nemestrina and Macaca fascicularis to analyze the organization of terminals and passing fibers in the STN. Results show a topographically organized prefrontal hyperdirect pathway in primates. Limbic areas project to the medial tip of the nucleus, straddling its border and extending into the lateral hypothalamus. Associative areas project to the medial half, motor areas to the lateral half. Limbic projections terminated primarily rostrally and motor projections more caudally. The extension of limbic projections into the lateral hypothalamus, suggests that this region be included in the STN. A high degree of convergence exists between projections from functionally diverse cortical areas, creating potentially important interfaces between terminal fields. Taken together, the results provide an anatomical substrate to extend the role of the hyperdirect pathway in models of basal ganglia function, and new keys for understanding deep brain stimulation effects on cognitive and motivational aspects of behavior. more...
- Published
- 2013
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9. Human and monkey ventral prefrontal fibers use the same organizational principles to reach their targets: tracing versus tractography.
- Author
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Jbabdi S, Lehman JF, Haber SN, and Behrens TE
- Subjects
- Adult, Animals, Brain Stem cytology, Brain Stem physiology, Data Interpretation, Statistical, Diffusion Tensor Imaging, Female, Gyrus Cinguli cytology, Gyrus Cinguli physiology, Humans, Image Processing, Computer-Assisted, Internal Capsule cytology, Internal Capsule physiology, Macaca fascicularis, Macaca mulatta, Male, Neural Pathways cytology, Neural Pathways physiology, Prefrontal Cortex cytology, Psychomotor Performance physiology, Reproducibility of Results, Species Specificity, Thalamus cytology, Thalamus physiology, Young Adult, Nerve Fibers physiology, Prefrontal Cortex physiology
- Abstract
This article is a comparative study of white matter projections from ventral prefrontal cortex (vPFC) between human and macaque brains. We test whether the organizational rules that vPFC connections follow in macaques are preserved in humans. These rules concern the trajectories of some of the white matter projections from vPFC and how the position of regions in the vPFC dictate the trajectories of their projections in the white matter. To address this question, we present a novel approach that combines direct tracer measurements of entire white matter trajectories in macaque monkeys with diffusion MRI tractography of both macaques and humans. The approach allows us to provide explicit validation of diffusion tractography and transfer tractography strategies across species to test the extent to which inferences from macaques can be applied to human neuroanatomy. Apart from one exception, we found a remarkable overlap between the two techniques in the macaque. Furthermore, the organizational principles followed by vPFC tracts in macaques are preserved in humans. more...
- Published
- 2013
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10. Rules ventral prefrontal cortical axons use to reach their targets: implications for diffusion tensor imaging tractography and deep brain stimulation for psychiatric illness.
- Author
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Lehman JF, Greenberg BD, McIntyre CC, Rasmussen SA, and Haber SN
- Subjects
- Animals, Deep Brain Stimulation, Diffusion Tensor Imaging, Macaca fascicularis, Macaca nemestrina, Male, Neural Pathways, Axons physiology, Brain Stem physiology, Neurons physiology, Prefrontal Cortex physiology, Thalamus physiology
- Abstract
The ventral prefrontal cortex (vPFC) is involved in reinforcement-based learning and is associated with depression, obsessive-compulsive disorder, and addiction. Neuroimaging is increasingly used to develop models of vPFC connections, to examine white matter (WM) integrity, and to target surgical interventions, including deep brain stimulation. We used primate (Macaca nemestrina/Macaca fascicularis) tracing studies and 3D reconstructions of WM tracts to delineate the rules vPFC projections follow to reach their targets. vPFC efferent axons travel through the uncinate fasciculus, connecting different vPFC regions and linking different functional regions. The uncinate fasciculus also is a conduit for vPFC fibers to reach other cortical bundles. Fibers in the internal capsule are organized according to destination. Thalamic fibers from each vPFC region travel dorsal to their brainstem fibers. The results show regional differences in the trajectories of fibers from different vPFC areas. Overall, the medial/lateral vPFC position dictates the route that fibers take to enter major WM tracts, as well as the position within specific tracts: axons from medial vPFC regions travel ventral to those from more lateral areas. This arrangement, coupled with dorsal/ventral organization of thalamic/brainstem fibers through the internal capsule, results in a complex mingling of thalamic and brainstem axons from different vPFC areas. Together, these data provide the foundation for dividing vPFC WM bundles into functional components and for predicting what is likely to be carried at different points through each bundle. These results also help determine the specific connections that are likely to be captured at different neurosurgical targets. more...
- Published
- 2011
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11. Low-pass filter properties of basal ganglia cortical muscle loops in the normal and MPTP primate model of parkinsonism.
- Author
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Rivlin-Etzion M, Marmor O, Saban G, Rosin B, Haber SN, Vaadia E, Prut Y, and Bergman H
- Subjects
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pharmacology, Action Potentials physiology, Action Potentials radiation effects, Animals, Behavior, Animal, Brain Mapping methods, Chlorocebus aethiops, Disease Models, Animal, Dose-Response Relationship, Radiation, Electric Stimulation methods, Globus Pallidus pathology, Globus Pallidus radiation effects, Magnetic Resonance Imaging methods, Motor Cortex pathology, Motor Cortex radiation effects, Movement radiation effects, Muscle, Skeletal drug effects, Muscle, Skeletal radiation effects, Neural Pathways pathology, Neural Pathways physiopathology, Neural Pathways radiation effects, Neurons physiology, Neurons radiation effects, Neurotoxins pharmacology, Reaction Time drug effects, Reaction Time physiology, Reaction Time radiation effects, Globus Pallidus physiopathology, Motor Cortex physiopathology, Muscle, Skeletal innervation, Parkinsonian Disorders pathology, Parkinsonian Disorders physiopathology
- Abstract
Oscillatory bursting activity is commonly found in the basal ganglia (BG) and the thalamus of the parkinsonian brain. The frequency of these oscillations is often similar to or higher than that of the parkinsonian tremor, but their relationship to the tremor and other parkinsonian symptoms is still under debate. We studied the frequency dependency of information transmission in the cortex-BG and cortex-periphery loops by recording simultaneously from multiple electrodes located in the arm-related primary motor cortex (MI) and in the globus pallidus (GP) of two vervet monkeys before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment and induction of parkinsonian symptoms. We mimicked the parkinsonian bursting oscillations by stimulating with 35 ms bursts given at different frequencies through microelectrodes located in MI or GP while recording the evoked neuronal and motor responses. In the normal state, microstimulation of MI or GP does not modulate the discharge rate in the other structure. However, the functional-connectivity between MI and GP is greatly enhanced after MPTP treatment. In the frequency domain, GP neurons usually responded equally to 1-15 Hz stimulation bursts in both states. In contrast, MI neurons demonstrated low-pass filter properties, with a cutoff frequency above 5 Hz for the MI stimulations, and below 5 Hz for the GP stimulations. Finally, muscle activation evoked by MI microstimulation was markedly attenuated at frequencies higher than 5 Hz. The low-pass properties of the pathways connecting GP to MI to muscles suggest that parkinsonian tremor is not directly driven by the BG 5-10 Hz burst oscillations despite their similar frequencies. more...
- Published
- 2008
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12. Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning.
- Author
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Haber SN, Kim KS, Mailly P, and Calzavara R
- Subjects
- Animals, Cerebral Cortex physiology, Conditioning, Psychological, Corpus Striatum physiology, Macaca fascicularis, Macaca nemestrina, Neural Pathways cytology, Neural Pathways physiology, Cerebral Cortex cytology, Corpus Striatum cytology, Decision Making physiology, Learning physiology, Motivation, Reward
- Abstract
The anterior cingulate and orbital cortices and the ventral striatum process different aspects of reward evaluation, whereas the dorsolateral prefrontal cortex and the dorsal striatum are involved in cognitive function. Collectively, these areas are critical to decision making. We mapped the striatal area that receives information about reward evaluation. We also explored the extent to which terminals from reward-related cortical areas converge in the striatum with those from cognitive regions. Using three-dimensional-rendered reconstructions of corticostriatal projection fields along with two-dimensional chartings, we demonstrate the reward and cognitive territories in the primate striatum and show the convergence between these cortical inputs. The results show two labeling patterns: a focal projection field that consists of densely distributed terminal patches, and a diffuse projection consisting of clusters of fibers, extending throughout a wide area of the striatum. Together, these projection fields demonstrate a remarkably large, rostral, reward-related striatal territory that reaches into the dorsal striatum. Fibers from different reward-processing and cognitive cortical areas occupy both separate and converging territories. Furthermore, the diffuse projection may serve a separate integrative function by broadly disseminating general cortical activity. These findings show that the rostral striatum is in a unique position to mediate different aspects of incentive learning. Furthermore, areas of convergence may be particularly sensitive to dopamine modulation during decision making and habit formation. more...
- Published
- 2006
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13. Dopamine replacement therapy does not restore the full spectrum of normal pallidal activity in the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine primate model of Parkinsonism.
- Author
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Heimer G, Rivlin-Etzion M, Bar-Gad I, Goldberg JA, Haber SN, and Bergman H
- Subjects
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Antiparkinson Agents administration & dosage, Chlorocebus aethiops, Female, Globus Pallidus drug effects, Macaca mulatta, Parkinsonian Disorders chemically induced, Recovery of Function drug effects, Species Specificity, Treatment Outcome, Action Potentials drug effects, Biological Clocks drug effects, Dopamine administration & dosage, Globus Pallidus physiopathology, Neurons drug effects, Parkinsonian Disorders drug therapy, Parkinsonian Disorders physiopathology
- Abstract
Current physiological studies emphasize the role of neuronal oscillations and synchronization in the pathophysiology of Parkinson's disease; however, little is known about their specific roles in the neuronal substrate of dopamine replacement therapy (DRT). We investigated oscillatory activity and correlations throughout the different states of levodopa-naive parkinsonism as well as "Off-On" and dyskinetic states of DRT in the external globus pallidum (GPe) of tremulous (vervet) and rigid-akinetic (macaque) monkeys and in the internal globus pallidum (GPi) of the vervet monkey. We found that, although oscillatory activity of cells and interneuronal correlation in both pallidal segments increases after induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and decreases in response to DRT, important differences exist between the two pallidal segments. In the GPi, the fraction of oscillatory cells and relative power of oscillations were significantly higher than in the GPe, and the dominant frequency was within the range of 7.5-13.5 Hz compared with a range of 4.5-7.5 Hz within the GPe. The interneuronal correlations were mostly oscillatory in the GPi, whereas at least half are non-oscillatory in the GPe. We demonstrate that the tremor characteristics after exposure to DRT do not resemble those of the normal or the levodopa-naive state. Moreover, although DRT reverses the MPTP-induced neuronal changes (rate, pattern, and pairwise correlations), the balance between GPe and GPi fails to restore. We therefore suggest that this imbalance reflects additional abnormal organization of the basal ganglia networks in response to dopamine replacement and may constitute the physiological substrate of the limitations and side effects of chronic DRT. more...
- Published
- 2006
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14. Defining the caudal ventral striatum in primates: cellular and histochemical features.
- Author
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Fudge JL and Haber SN
- Subjects
- Acetylcholinesterase biosynthesis, Amygdala cytology, Amygdala metabolism, Animals, Antigens, Differentiation biosynthesis, Calbindins, Corpus Striatum metabolism, Histocytochemistry, Limbic System cytology, Macaca, Proto-Oncogene Proteins c-bcl-2 biosynthesis, S100 Calcium Binding Protein G biosynthesis, Substance P biosynthesis, Terminology as Topic, Tyrosine 3-Monooxygenase biosynthesis, Corpus Striatum cytology
- Abstract
Afferents from the amygdala help to define the ventral striatum and mediate goal-directed behaviors. In addition to well known inputs to the classic ventral striatum, the amygdala also projects to the caudoventral striatum and amygdalostriatal area. We examined whether the primate caudoventral striatum and amygdalostriatal area can be considered part of the "ventral" striatum based on cellular and histochemical features found in the classic rostral ventral striatum. We used several histochemical stains, including calbindin-D28k, a marker of the shell compartment, acetylcholinesterase, substance P, tyrosine hydroxylase, and Bcl-2, a marker of immature neurons, to examine this question. Our results indicate that the lateral amygdalostriatal area and caudoventral striatum are "striatal like" based on intermediate to high acetylcholinesterase and tyrosine hydroxylase levels. The lateral amygdalostriatal area is chemically similar to the shell, whereas the caudoventral striatum more closely resembles the striatum outside the shell. In contrast, the medial amygdalostriatal area is more related to the central amygdaloid nucleus than to the striatum. Bcl-2 immunoreactivity is associated with granular islands and medium-sized cells in the vicinity of the ventral striatum both rostrally and caudally. Together, the caudal ventral striatum has a histochemical and cellular organization similar to that of the rostral ventral striatum, consistent with their common innervation by the amygdala and other ventral structures. In addition, Bcl-2 is expressed in and near both poles of the ventral striatum, suggesting that these areas maintain a heightened capacity for growth and plasticity compared with other striatal sectors. more...
- Published
- 2002
15. Thalamic relay nuclei of the basal ganglia form both reciprocal and nonreciprocal cortical connections, linking multiple frontal cortical areas.
- Author
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McFarland NR and Haber SN
- Subjects
- Amino Acids, Animals, Cell Count, Dextrans, Fluoresceins, Fluorescent Dyes, Macaca nemestrina, Mediodorsal Thalamic Nucleus anatomy & histology, Microinjections, Nerve Fibers physiology, Silver Staining, Ventral Thalamic Nuclei anatomy & histology, Wheat Germ Agglutinins, Basal Ganglia anatomy & histology, Frontal Lobe anatomy & histology, Neural Pathways anatomy & histology, Thalamic Nuclei anatomy & histology
- Abstract
Thalamic relay nuclei transmit basal ganglia output to the frontal cortex, forming the last link in corticobasal ganglia circuitry. The thalamus regulates cortical activity through differential laminar connections, providing not only feedback, but also initiating "feedforward" loops, via nonreciprocal projections, that influence higher cortical areas. This study examines the organization of thalamic connections with cortex from basal ganglia relay nuclei, including ventral anterior (VA), ventral lateral (VL), and mediodorsal (MD) nuclei, in the Macaque monkey. Anterograde and bidirectional tracer injections ([3H]-amino acids, dextran conjugates of Fluorescein, Lucifer Yellow or FluoroRuby, or wheat germ agglutinin) into discrete VA/VL, MD, and frontal cortical sites demonstrate specific thalamocortical connections. VL projections target caudal motor areas (primary, supplementary, and caudal premotor areas), whereas VA projections target more rostral premotor areas (including cingulate and presupplementary motor areas) and MD projects to dorsolateral and orbital prefrontal cortices. Thalamocortical projections innervate cortical layers I and III, and to a lesser extent, layer V. In motor areas layer I projections are more extensive than those to layer III (and V). The complex laminar organization of projections from specific thalamic sites suggests differential regulation of cortical function. Injections of bidirectional tracers into thalamic and frontal cortical sites also show that in comparison to thalamocortical projections, corticothalamic projections to VA-VL and MD are more widespread. These findings demonstrate both reciprocal and nonreciprocal components to the thalamo-cortico-thalamic relay. Together, these experiments indicate a dual role for VA-VL and MD nuclei: (1) to relay basal ganglia output within specific cortical circuits and (2) to mediate information flow between cortical circuits. more...
- Published
- 2002
16. Enhanced synchrony among primary motor cortex neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease.
- Author
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Goldberg JA, Boraud T, Maraton S, Haber SN, Vaadia E, and Bergman H
- Subjects
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Action Potentials, Animals, Arm physiopathology, Biomechanical Phenomena, Chlorocebus aethiops, Corpus Striatum drug effects, Corpus Striatum pathology, Corpus Striatum physiopathology, Disease Models, Animal, Disease Progression, Dopamine Agents, Electric Stimulation methods, Electromyography, Female, Globus Pallidus drug effects, Globus Pallidus physiopathology, Immunohistochemistry, Macaca fascicularis, Motor Cortex drug effects, Motor Cortex pathology, Motor Skills, Muscle Rigidity physiopathology, Parkinson Disease, Secondary chemically induced, Range of Motion, Articular drug effects, Tyrosine 3-Monooxygenase biosynthesis, Motor Cortex physiopathology, Neurons drug effects, Neurons physiology, Parkinson Disease, Secondary physiopathology
- Abstract
Primary motor cortex (MI) neurons discharge vigorously during voluntary movement. A cardinal symptom of Parkinson's disease (PD) is poverty of movement (akinesia). Current models of PD thus hypothesize that increased inhibitory pallidal output reduces firing rates in frontal cortex, including MI, resulting in akinesia and muscle rigidity. We recorded the simultaneous spontaneous discharge of several neurons in the arm-related area of MI of two monkeys and in the globus pallidus (GP) of one of the two. Accelerometers were fastened to the forelimbs to detect movement, and surface electromyograms were recorded from the contralateral arm of one monkey. The recordings were conducted before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rendering the animals severely akinetic and rigid with little or no tremor. The mean spontaneous MI rates during periods of immobility (four to five spikes/sec) did not change after MPTP; however, in this parkinsonian state, MI neurons discharged in long bursts (sometimes >2 sec long). These bursts were synchronized across many cells but failed to elicit detectable movement, indicating that even robust synchronous MI discharge need not result in movement. These synchronized population bursts were absent from the GP and were on a larger timescale than oscillatory synchrony found in the GP of tremulous MPTP primates, suggesting that MI parkinsonian synchrony arises independently of basal ganglia dynamics. After MPTP, MI neurons responded more vigorously and with less specificity to passive limb movement. Abnormal MI firing patterns and synchronization, rather than reduced firing rates, may underlie PD akinesia and persistent muscle rigidity. more...
- Published
- 2002
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17. Striatal responses to partial dopaminergic lesion: evidence for compensatory sprouting.
- Author
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Song DD and Haber SN
- Subjects
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pharmacology, Animals, Corpus Striatum drug effects, GAP-43 Protein genetics, Gene Expression Regulation drug effects, Macaca nemestrina, Nerve Fibers drug effects, Nerve Fibers physiology, Nerve Fibers ultrastructure, RNA, Messenger genetics, Reference Values, Transcription, Genetic drug effects, Tyrosine 3-Monooxygenase analysis, Corpus Striatum physiology, Dopamine metabolism, Enkephalins genetics, Protein Precursors genetics
- Abstract
Dopaminergic lesions result in the acute loss of striatal dopamine content, the loss of tyrosine hydroxylase-immunoreactive fibers, upregulation of preproenkephalin mRNA expression, and compensatory changes in the synthesis and metabolism of dopamine. Despite the severe loss of fine tyrosine hydroxylase-immunoreactive fibers, larger fibers persist. We found that some tyrosine hydroxylase fiber types increase their branching and become thicker after partial lesion. To determine whether the remaining tyrosine hydroxylase fibers were degenerative or part of a compensatory response, we morphologically characterized striatal tyrosine hydroxylase fibers and compared them to silver-stained degenerative structures. Branched and large tyrosine hydroxylase fiber types were nondegenerative. Furthermore, normal preproenkephalin mRNA expression was maintained despite severe overall loss of tyrosine hydroxylase fibers in striatal regions with abundant branching, whereas preproenkephalin mRNA expression increased in severely depleted regions that lacked branched fibers, indicating that branching or sprouting was involved in the compensation for dopamine depletion and the maintenance of normal preproenkephalin expression. In support of compensatory sprouting by tyrosine hydroxylase fibers, mRNA for growth associated protein-43 was upregulated in dopaminergic midbrain cells. We conclude that an important compensatory response to partial dopaminergic depletion is the formation of new branches or sprouting. more...
- Published
- 2000
18. Convergent inputs from thalamic motor nuclei and frontal cortical areas to the dorsal striatum in the primate.
- Author
-
McFarland NR and Haber SN
- Subjects
- Animals, Fluorescent Dyes, Gyrus Cinguli cytology, Isoquinolines, Macaca mulatta, Macaca nemestrina, Motor Neurons cytology, Neural Pathways, Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate, Motor Cortex cytology, Neostriatum cytology, Ventral Thalamic Nuclei cytology
- Abstract
Current models of basal ganglia circuitry primarily associate the ventral thalamic nuclei with relaying basal ganglia output to the frontal cortex. However, some studies have demonstrated projections from the ventral anterior (VA) and ventral lateral (VL) thalamic nuclei to the striatum, suggesting that these nuclei directly modulate the striatum. VA/VL nuclei have specific connections with primary, supplementary, premotor, and cingulate motor cortices indicating their involvement in motor function. These areas mediate different aspects of motor control such as movement execution, motor learning, and sensorimotor integration. Increasing evidence indicates that functionally related motor areas have convergent projections to the dorsal striatum, suggesting that integration of different aspects of motor control occur at the level of the striatum. This study examines the organization of VA/VL thalamic inputs to the dorsal "motor" striatum to determine how this afferent projection is organized with respect to corticostriatal afferents from motor, premotor, and cingulate motor areas. Motor cortical projections to specific dorsal striatal regions arose from multiple areas, including components from primary motor, premotor, supplementary, and cingulate motor areas. Diverse motor cortical projections to a given dorsal striatal region indicated convergence of functionally related corticostriatal motor pathways. Most dorsal striatal sites received dense thalamic inputs from the VL pars oralis nucleus. Additional thalamostriatal projections arose from VA, VL pars caudalis, and ventral posterior lateral pars oralis nuclei and Olszewski's Area X. Our results provide evidence for convergent striatal projections from interconnected ventral thalamic and cortical motor areas, suggesting that these afferents modulate the same striatal output circuits. more...
- Published
- 2000
19. Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum.
- Author
-
Haber SN, Fudge JL, and McFarland NR
- Subjects
- Animals, Macaca mulatta, Macaca nemestrina, Microinjections, Molecular Probes, Nerve Fibers, Neural Pathways, Neurons ultrastructure, Phytohemagglutinins, Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate, Corpus Striatum cytology, Frontal Lobe cytology, Substantia Nigra cytology, Ventral Tegmental Area cytology
- Abstract
Clinical manifestations in diseases affecting the dopamine system include deficits in emotional, cognitive, and motor function. Although the parallel organization of specific corticostriatal pathways is well documented, mechanisms by which dopamine might integrate information across different cortical/basal ganglia circuits are less well understood. We analyzed a collection of retrograde and anterograde tracing studies to understand how the striatonigrostriatal (SNS) subcircuit directs information flow between ventromedial (limbic), central (associative), and dorsolateral (motor) striatal regions. When viewed as a whole, the ventromedial striatum projects to a wide range of the dopamine cells and receives a relatively small dopamine input. In contrast, the dorsolateral striatum (DLS) receives input from a broad expanse of dopamine cells and has a confined input to the substantia nigra (SN). The central striatum (CS) receives input from and projects to a relatively wide range of the SN. The SNS projection from each striatal region contains three substantia nigra components: a dorsal group of nigrostriatal projecting cells, a central region containing both nigrostriatal projecting cells and its reciprocal striatonigral terminal fields, and a ventral region that receives a specific striatonigral projection but does not contain its reciprocal nigrostriatal projection. Examination of results from multiple tracing experiments simultaneously demonstrates an interface between different striatal regions via the midbrain dopamine cells that forms an ascending spiral between regions. The shell influences the core, the core influences the central striatum, and the central striatum influences the dorsolateral striatum. This anatomical arrangement creates a hierarchy of information flow and provides an anatomical basis for the limbic/cognitive/motor interface via the ventral midbrain. more...
- Published
- 2000
20. Dopamine neurons make glutamatergic synapses in vitro.
- Author
-
Sulzer D, Joyce MP, Lin L, Geldwert D, Haber SN, Hattori T, and Rayport S
- Subjects
- Animals, Brain cytology, Cells, Cultured, Immunohistochemistry, Macaca nemestrina, Male, Microscopy, Electron, Presynaptic Terminals physiology, Rats, Staining and Labeling, Dopamine physiology, Glutamic Acid physiology, Neurons physiology, Synapses physiology
- Abstract
Interactions between dopamine and glutamate play prominent roles in memory, addiction, and schizophrenia. Several lines of evidence have suggested that the ventral midbrain dopamine neurons that give rise to the major CNS dopaminergic projections may also be glutamatergic. To examine this possibility, we double immunostained ventral midbrain sections from rat and monkey for the dopamine-synthetic enzyme tyrosine hydroxylase and for glutamate; we found that most dopamine neurons immunostained for glutamate, both in rat and monkey. We then used postnatal cell culture to examine individual dopamine neurons. Again, most dopamine neurons immunostained for glutamate; they were also immunoreactive for phosphate-activated glutaminase, the major source of neurotransmitter glutamate. Inhibition of glutaminase reduced glutamate staining. In single-cell microculture, dopamine neurons gave rise to varicosities immunoreactive for both tyrosine hydroxylase and glutamate and others immunoreactive mainly for glutamate, which were found near the cell body. At the ultrastructural level, dopamine neurons formed occasional dopaminergic varicosities with symmetric synaptic specializations, but they more commonly formed nondopaminergic varicosities with asymmetric synaptic specializations. Stimulation of individual dopamine neurons evoked a fast glutamatergic autaptic EPSC that showed presynaptic inhibition caused by concomitant dopamine release. Thus, dopamine neurons may exert rapid synaptic actions via their glutamatergic synapses and slower modulatory actions via their dopaminergic synapses. Together with evidence for glutamate cotransmission in serotonergic raphe neurons and noradrenergic locus coeruleus neurons, the present results suggest that glutamatergic cotransmission may be the rule for central monoaminergic neurons. more...
- Published
- 1998
21. Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate.
- Author
-
Chikama M, McFarland NR, Amaral DG, and Haber SN
- Subjects
- Animals, Gyrus Cinguli cytology, Limbic System cytology, Neural Pathways, Prefrontal Cortex cytology, Silver Staining, Taste physiology, Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate, Cerebral Cortex cytology, Corpus Striatum cytology, Macaca mulatta anatomy & histology, Macaca nemestrina anatomy & histology
- Abstract
We examined the striatal projections from different cytoarchitectonic regions of the insular cortex using anterograde and retrograde techniques. The shell and medial ventral striatum receive inputs primarily from the agranular and ventral dysgranular insula. The central ventral striatum receives inputs primarily from the dorsal agranular and dysgranular insula. Projections to the central ventral striatum originate from more posterior and dorsal insular regions than projections to the medial ventral striatum. The dorsolateral striatum receives projections primarily from the dorsal dysgranular and granular insula. These results show that cytoarchitectonically less differentiated (agranular) insular regions project to the ventromedial "limbic" part of the ventral striatum, whereas more differentiated (granular) insular regions project to the dorsolateral "sensorimotor" part of the striatum. The finding that the ventral "limbic" striatum receives inputs from less differentiated regions of the insula is consistent with the general principle that less differentiated cortical regions project primarily to the "limbic" striatum. Functionally, the ventral striatum receives insular projections primarily related to integrating feeding behavior with rewards and memory, whereas the dorsolateral striatum receives insular inputs related to the somatosensation. Information regarding food acquisition in the insula may be sent to the intermediate area of the striatum. more...
- Published
- 1997
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