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1.
J Comp Neurol ; 529(14): 3410-3428, 2021 10.
Article in English | MEDLINE | ID: mdl-34176123

ABSTRACT

The dorsal ventricular ridge (DVR), which is the largest component of the avian pallium, contains discrete partitions receiving tectovisual, auditory, and trigeminal ascending projections. Recent studies have shown that the auditory and the tectovisual regions can be regarded as complexes composed of three highly interconnected layers: an internal senso-recipient one, an intermediate afferent/efferent one, and a more external re-entrant one. Cells located in homotopic positions in each of these layers are reciprocally linked by an interlaminar loop of axonal processes, forming columnar-like local circuits. Whether this type of organization also extends to the trigemino-recipient DVR is, at present, not known. This question is of interest, since afferents forming this sensory pathway, exceptional among amniotes, are not thalamic but rhombencephalic in origin. We investigated this question by placing minute injections of neural tracers into selected locations of vital slices of the chicken telencephalon. We found that neurons of the trigemino-recipient nucleus basorostralis pallii (Bas) establish reciprocal, columnar and homotopical projections with cells located in the overlying ventral mesopallium (MV). "Column-forming" axons originated in B and MV terminate also in the intermediate strip, the fronto-trigeminal nidopallium (NFT), in a restricted manner. We also found that the NFT and an internal partition of B originate substantial, coarse-topographic projections to the underlying portion of the lateral striatum. We conclude that all sensory areas of the DVR are organized according to a common neuroarchitectonic motif, which bears a striking resemblance to that of the radial/laminar intrinsic circuits of the sensory cortices of mammals.


Subject(s)
Chickens/physiology , Nerve Net/anatomy & histology , Nerve Net/physiology , Trigeminal Nuclei/anatomy & histology , Trigeminal Nuclei/physiology , Afferent Pathways/physiology , Animals , Axons/physiology , Brain Mapping , Female , Immunohistochemistry , Male , Neostriatum/anatomy & histology , Neostriatum/physiology , Neural Pathways/physiology , Sensation/physiology
2.
Cereb Cortex ; 31(8): 3579-3591, 2021 07 05.
Article in English | MEDLINE | ID: mdl-33754629

ABSTRACT

The rate of cesarean section (CS) delivery has steadily increased over the past decades despite epidemiological studies reporting higher risks of neonatal morbidity and neurodevelopmental disorders. Yet, little is known about the immediate impact of CS birth on the brain, hence the need of experimental studies to evaluate brain parameters following this mode of delivery. Using the solvent clearing method iDISCO and 3D imaging technique, we report that on the day of birth, whole-brain, hippocampus, and striatum volumes are reduced in CS-delivered as compared to vaginally-born mice, with a stronger effect observed in preterm CS pups. These results stress the impact of CS delivery, at term or preterm, during parturition and at birth. In contrast, cellular activity and apoptosis are reduced in mice born by CS preterm but not term, suggesting that these early-life processes are only impacted by the combination of preterm birth and CS delivery.


Subject(s)
Brain/anatomy & histology , Cesarean Section/adverse effects , Delivery, Obstetric/adverse effects , Premature Birth , Animals , Animals, Newborn , Apoptosis , Brain Chemistry , Caspase 3/metabolism , Female , Gestational Age , Hippocampus/anatomy & histology , Hippocampus/metabolism , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Male , Mice , Neostriatum/anatomy & histology , Neostriatum/metabolism , Pregnancy , Proto-Oncogene Proteins c-fos/biosynthesis , Proto-Oncogene Proteins c-fos/metabolism
3.
Int J Dev Neurosci ; 81(1): 60-70, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33135304

ABSTRACT

Neonatal hypoxia-ischemia (HI) can lead to cognitive impairments and motor dysfunction. Acrobatic exercises (AE) were proposing as therapeutic option to manage HI motor deficits, however, the cognitive effects after this treatment are still poorly understood. Therefore, we evaluated the effects of AE protocol on memory impairments and brain plasticity markers after Rice-Vannucci HI rodent model. Wistar rats on the 7th postnatal day (PND) were submitted to HI model and after weaning (PND22) were trained for 5 weeks with AE protocol, then subsequently submitted to cognitive tests. Our results showed recovery in novel object recognition (NOR) memory, but not, spatial Morris Water Maze (WM) memory after AE treatment in HI rats. BDNF and synaptophysin neuroplasticity markers indicate plastic alterations in the hippocampus and striatum, with maintenance of synaptophysin despite the reduction of total volume tissue, besides, hippocampal HI-induced ipsilateral BDNF increased, and striatum contralateral BDNF decreased were noted. Nevertheless, the exercise promoted functional recovery and seems to be a promising strategy for HI treatment, however, future studies identifying neuroplastic pathway for this improvement are needed.


Subject(s)
Hypoxia-Ischemia, Brain/psychology , Hypoxia-Ischemia, Brain/rehabilitation , Memory Disorders/psychology , Memory Disorders/rehabilitation , Physical Conditioning, Animal/psychology , Recognition, Psychology , Animals , Animals, Newborn , Atrophy , Brain-Derived Neurotrophic Factor/metabolism , Hippocampus/anatomy & histology , Maze Learning , Motor Skills , Neostriatum/anatomy & histology , Psychomotor Performance , Rats , Rats, Wistar , Recovery of Function , Spatial Memory , Synaptophysin/metabolism
4.
J Neurosci ; 41(2): 331-341, 2021 01 13.
Article in English | MEDLINE | ID: mdl-33214318

ABSTRACT

In complex everyday environments, action selection is critical for optimal goal-directed behavior. This refers to the process of choosing a proper action from the range of possible alternatives. The neural mechanisms underlying action selection and how these are affected by normal aging remain to be elucidated. In the present cross-sectional study, we studied processes of effector selection during a multilimb reaction time task in a lifespan sample of healthy human adults (N = 89; 20-75 years; 48 males, 41 females). Participants were instructed to react as quickly and accurately as possible to visually cued stimuli representing single-limb or combined upper and/or lower limb motions. Diffusion MRI was used to study structural connectivity between prefrontal and striatal regions as critical nodes for action selection. Behavioral findings revealed that increasing age was associated with slowing of action selection performance. At the neural level, aging had a negative impact on prefronto-striatal connectivity. Importantly, mediation analyses revealed that the negative association between action selection performance and age was mediated by prefronto-striatal connectivity, specifically the connections between left rostral medial frontal gyrus and left nucleus accumbens as well as right frontal pole and left caudate. These results highlight the potential role of prefronto-striatal white matter decline in poorer action selection performance of older adults.SIGNIFICANCE STATEMENT As a result of enhanced life expectancy, researchers have devoted increasing attention to the study of age-related alterations in cognitive and motor functions. Here we study associations between brain structure and behavior to reveal the impact of central neural white matter changes as a function of normal aging on action selection performance. We demonstrate the critical role of a reduction in prefronto-striatal structural connectivity in accounting for action selection performance deficits in healthy older adults. Preserving this cortico-subcortical pathway may be critical for behavioral flexibility and functional independence in older age.


Subject(s)
Neostriatum/anatomy & histology , Neostriatum/physiology , Neural Pathways/anatomy & histology , Neural Pathways/physiology , Prefrontal Cortex/anatomy & histology , Prefrontal Cortex/physiology , Adult , Aged , Aging/physiology , Caudate Nucleus/physiology , Cross-Sectional Studies , Cues , Decision Making , Diffusion Magnetic Resonance Imaging , Female , Humans , Male , Middle Aged , Movement/physiology , Neostriatum/growth & development , Neural Pathways/growth & development , Nucleus Accumbens/physiology , Photic Stimulation , Prefrontal Cortex/growth & development , Reaction Time/physiology , Young Adult
5.
Hum Brain Mapp ; 41(16): 4641-4661, 2020 11.
Article in English | MEDLINE | ID: mdl-32757349

ABSTRACT

Internal and external segments of globus pallidus (GP) exert different functions in basal ganglia circuitry, despite their main connectional systems share the same topographical organization, delineating limbic, associative, and sensorimotor territories. The identification of internal GP sensorimotor territory has therapeutic implications in functional neurosurgery settings. This study is aimed at assessing the spatial coherence of striatopallidal, subthalamopallidal, and pallidothalamic pathways by using tractography-derived connectivity-based parcellation (CBP) on high quality diffusion MRI data of 100 unrelated healthy subjects from the Human Connectome Project. A two-stage hypothesis-driven CBP approach has been carried out on the internal and external GP. Dice coefficient between functionally homologous pairs of pallidal maps has been computed. In addition, reproducibility of parcellation according to different pathways of interest has been investigated, as well as spatial relations between connectivity maps and existing optimal stimulation points for dystonic patients. The spatial organization of connectivity clusters revealed anterior limbic, intermediate associative and posterior sensorimotor maps within both internal and external GP. Dice coefficients showed high degree of coherence between functionally similar maps derived from the different bundles of interest. Sensorimotor maps derived from the subthalamopallidal pathway resulted to be the nearest to known optimal pallidal stimulation sites for dystonic patients. Our findings suggest that functionally homologous afferent and efferent connections may share similar spatial territory within the GP and that subcortical pallidal connectional systems may have distinct implications in the treatment of movement disorders.


Subject(s)
Cerebral Cortex/anatomy & histology , Diffusion Tensor Imaging , Globus Pallidus/anatomy & histology , Neostriatum/anatomy & histology , Nerve Net/anatomy & histology , Subthalamic Nucleus/anatomy & histology , Thalamus/anatomy & histology , Ventral Striatum/anatomy & histology , Adult , Afferent Pathways , Cerebral Cortex/diagnostic imaging , Efferent Pathways , Female , Globus Pallidus/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Male , Neostriatum/diagnostic imaging , Nerve Net/diagnostic imaging , Subthalamic Nucleus/diagnostic imaging , Thalamus/diagnostic imaging , Ventral Striatum/diagnostic imaging , Young Adult
6.
Cell Rep ; 29(13): 4320-4333.e5, 2019 12 24.
Article in English | MEDLINE | ID: mdl-31875543

ABSTRACT

The striatum is organized into two major outputs formed by striatal projection neuron (SPN) subtypes with distinct molecular identities. In addition, histochemical division into patch and matrix compartments represents an additional spatial organization, proposed to mirror a motor-motivation regionalization. To map the molecular diversity of patch versus matrix SPNs, we genetically labeled mu opioid receptor (Oprm1) expressing neurons and performed single-nucleus RNA sequencing. This allowed us to establish molecular definitions of patch, matrix, and exopatch SPNs, as well as identification of Col11a1+ striatonigral SPNs. At the tissue level, mapping the expression of candidate markers reveals organization of spatial domains, which are conserved in the non-human primate brain. The spatial markers are cell-type independent and instead represent a spatial code found across all SPNs within a spatial domain. The spatiomolecular map establishes a formal system for targeting and studying striatal subregions and SPNs subtypes, beyond the classical striatonigral and striatopallidal division.


Subject(s)
Neostriatum/anatomy & histology , Neostriatum/metabolism , Animals , Collagen Type XI/metabolism , Female , Male , Mice, Inbred C57BL , Mice, Transgenic , Neurons/metabolism , Receptors, Opioid, mu/metabolism
7.
Aggress Behav ; 43(3): 230-240, 2017 May.
Article in English | MEDLINE | ID: mdl-27766650

ABSTRACT

Verbal and physical aggression begin early in life and steadily decline thereafter in normal development. As a result, elevated aggressive behavior in adolescence may signal atypical development and greater vulnerability for negative mental and health outcomes. Converging evidence suggests that brain disturbances in regions involved in impulse control, emotional regulation, and sensation seeking may contribute to heightened aggression. However, little is known regarding the neural mechanisms underlying subtypes of aggression (i.e., proactive and reactive aggression) and whether they differ between males and females. Using a sample of 106 14-year-old adolescent twins, this study found that striatal enlargement was associated with both proactive and reactive aggression. We also found that volumetric alterations in several frontal regions including smaller middle frontal and larger orbitofrontal cortex were correlated with higher levels of aggression in adolescent twins. In addition, cortical thickness analysis showed that thickness alterations in many overlapping regions including middle frontal, superior frontal, and anterior cingulate cortex and temporal regions were associated with aggression in adolescent twins. Results support the involvement of fronto-limbic-striatal circuit in the etiology of aggression during adolescence. Aggr. Behav. 43:230-240, 2017. © 2016 Wiley Periodicals, Inc.


Subject(s)
Adolescent Behavior/physiology , Aggression/physiology , Cerebral Cortex/anatomy & histology , Neostriatum/anatomy & histology , Adolescent , Female , Gyrus Cinguli/anatomy & histology , Humans , Magnetic Resonance Imaging , Male , Occipital Lobe/anatomy & histology , Prefrontal Cortex/anatomy & histology
8.
Neurobiol Learn Mem ; 134 Pt B: 400-7, 2016 10.
Article in English | MEDLINE | ID: mdl-27614142

ABSTRACT

Pregnancy is accompanied by prolonged exposure to high estrogen levels. Animal studies have shown that estrogen influences navigation strategies and, hence, affects navigation performance. High estrogen levels are related to increased use of hippocampal-based allocentric strategies and decreased use of striatal-based egocentric strategies. In humans, associations between hormonal shifts and navigation strategies are less well studied. This study compared 30 peripartal women (mean age 28years) to an age-matched control group on allocentric versus egocentric navigation performance (measured in the last month of pregnancy) and gray matter volume (measured within two months after delivery). None of the women had a previous pregnancy before study participation. Relative to controls, pregnant women performed less well in the egocentric condition of the navigation task, but not the allocentric condition. A whole-brain group comparison revealed smaller left striatal volume (putamen) in the peripartal women. Across the two groups, left striatal volume was associated with superior egocentric over allocentric performance. Limited by the cross-sectional study design, the findings are a first indication that human pregnancy might be accompanied by structural brain changes in navigation-related neural systems and concomitant changes in navigation strategy.


Subject(s)
Neostriatum/anatomy & histology , Postpartum Period , Pregnancy/physiology , Spatial Learning/physiology , Spatial Navigation/physiology , Adult , Female , Humans , Magnetic Resonance Imaging , Neostriatum/diagnostic imaging , Pregnancy/metabolism , Pregnancy Trimester, Third , Putamen/anatomy & histology , Putamen/diagnostic imaging , Young Adult
9.
Neuroimage ; 120: 382-93, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26196668

ABSTRACT

Projections from the substantia nigra and striatum traverse through the pallidum on the way to their targets. To date, in vivo characterization of these pathways remains elusive. Here we used high angular resolution diffusion imaging (N=138) to study the characteristics and structural subcompartments of the human pallidum. Our central result shows that the diffusion orientation distribution functions within the pallidum are asymmetrically oriented in a dorsal to dorsolateral direction, consistent with the orientation of underlying fiber systems. We also observed systematic differences in the diffusion signal between the two pallidal segments. Compared to the outer pallidal segment, the internal segment has more peaks in the diffusion orientation distribution and stronger anisotropy in the primary fiber direction, consistent with known cellular differences between the underlying nuclei. These differences in orientation, complexity, and degree of anisotropy are sufficiently robust to automatically segment the pallidal nuclei using diffusion properties. We characterize these patterns in one data set using diffusion spectrum imaging and replicate in a separate sample of subjects imaged using multi-shell imaging, highlighting the reliability of these diffusion patterns within pallidal nuclei. Thus the gray matter diffusion signal can be useful as an in vivo measure of the collective efferent pathways running through the human pallidum.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Globus Pallidus/anatomy & histology , Neostriatum/anatomy & histology , Substantia Nigra/anatomy & histology , Adolescent , Adult , Efferent Pathways/anatomy & histology , Female , Humans , Male , Young Adult
10.
Proc Natl Acad Sci U S A ; 112(29): E3765-74, 2015 Jul 21.
Article in English | MEDLINE | ID: mdl-26100897

ABSTRACT

Adolescence is a developmental period associated with an increase in impulsivity. Impulsivity is a multidimensional construct, and in this study we focus on one of the underlying components: impatience. Impatience can result from (i) disregard of future outcomes and/or (ii) oversensitivity to immediate rewards, but it is not known which of these evaluative processes underlie developmental changes. To distinguish between these two causes, we investigated developmental changes in the structural and functional connectivity of different frontostriatal tracts. We report that adolescents were more impatient on an intertemporal choice task and reported less future orientation, but not more present hedonism, than young adults. Developmental increases in structural connectivity strength in the right dorsolateral prefrontal tract were related to increased negative functional coupling with the striatum and an age-related decrease in discount rates. Our results suggest that mainly increased control, and the integration of future-oriented thought, drives the reduction in impatience across adolescence.


Subject(s)
Impulsive Behavior/physiology , Neostriatum/physiology , Neural Pathways/physiology , Adolescent , Adult , Age Factors , Child , Choice Behavior , Diffusion Tensor Imaging , Female , Humans , Magnetic Resonance Imaging , Male , Neostriatum/anatomy & histology , Reward , Task Performance and Analysis , Young Adult
11.
Neurobiol Learn Mem ; 117: 51-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24858182

ABSTRACT

The striatum is critical for reward-guided and habitual behavior. Anatomical and interference studies suggest a functional heterogeneity within striatum. Medial regions, such as nucleus accumbens core and dorsal medial striatum play roles in goal-directed behavior, while dorsal lateral striatum is critical for control of habitual action. Subdivisions of striatum are topographically connected with different cortical and subcortical structures forming channels that carry information related to limbic, associative, and sensorimotor functions. Here, we describe data showing that as one progresses from ventral-medial to dorsal-lateral striatum, there is a shift from more prominent value encoding to activity more closely related to associative and motor aspects of decision-making. In addition, we will describe data suggesting that striatal circuits work in parallel to control behavior and that regions within striatum can compensate for each other when functions are disrupted.


Subject(s)
Decision Making/physiology , Neostriatum/physiology , Nucleus Accumbens/physiology , Reward , Animals , Humans , Macaca mulatta , Neostriatum/anatomy & histology , Nucleus Accumbens/anatomy & histology , Psychomotor Performance , Rats , Ventral Striatum/anatomy & histology , Ventral Striatum/physiology
12.
Mol Brain ; 7: 83, 2014 Nov 18.
Article in English | MEDLINE | ID: mdl-25406675

ABSTRACT

BACKGROUND: The basal ganglia (BG) are a complex network of subcortical nuclei involved in the coordination and integration of the motor activity. Although these independent anatomical structures are functionally related, the proteome present in each isolated nucleus remains largely unexplored. In order to analyse the BG proteome in a large-scale format, we used a multi-dimensional fractionation approach which combines isolation of anatomically-defined nuclei, and protein/peptide chromatographic fractionation strategies coupled to mass spectrometry. RESULTS: Using this workflow, we have obtained a proteomic expression profile across striatum and globus pallidus structures among which 1681 proteins were located in caudate nucleus (CN), 1329 in putamen, 1419 in medial globus pallidus (GPi), and 1480 in lateral globus pallidus (GPe), establishing a BG reference proteome to a depth of 2979 unique proteins. Protein interactome mapping highlighted significant clustering of common proteins in striatal and pallidal structures, contributing to oxidative phosphorylation, protein degradation and neurotrophin signalling pathways. In silico analyses emphasized specific pathways represented in striatal and pallidal structures highlighting 5-hydroxytryptamine degradation, synaptic vesicle trafficking, and dopamine, metabotropic glutamate and muscarinic acetylcholine receptor pathways. Additional bioinformatic analyses also revealed that: i) nearly 4% of identified proteins have been previously associated to neurodegenerative syndromes, ii) 11% of protein set tends to localize to synaptic terminal, and iii) 20% of identified proteins were also localized in cerebrospinal fluid (CSF). CONCLUSIONS: Overall, the anatomo-proteomic profiling of BG complements the anatomical atlas of the human brain transcriptome, increasing our knowledge about the molecular basis of the BG and the etiology of the movement disorders.


Subject(s)
Basal Ganglia/metabolism , Globus Pallidus/anatomy & histology , Globus Pallidus/metabolism , Neostriatum/metabolism , Proteomics , Adult , Basal Ganglia/anatomy & histology , Biomarkers/metabolism , Databases, Protein , Gene Expression Profiling , Gene Ontology , Humans , Male , Mass Spectrometry , Middle Aged , Neostriatum/anatomy & histology , Neurons/metabolism , Protein Interaction Mapping , Synaptosomes/metabolism , Transcriptome/genetics
13.
Neuroimage ; 97: 321-32, 2014 Aug 15.
Article in English | MEDLINE | ID: mdl-24736176

ABSTRACT

The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer's disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, supplementary motor area and pre-supplementary motor area, a network of brain regions that respond to salient stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS showed stronger positive connectivity with the ventral caudate and medial orbitofrontal cortex, areas implicated in reward processing and motivated behavior. Furthermore, the BNM and VS each showed extensive negative connectivity with visual and lateral prefrontal cortices. Together, the distinct cerebral functional connectivities support the role of the BNM in arousal, saliency responses and cognitive motor control and the VS in reward related behavior. Considering the importance of BNM in age-related cognitive decline, we explored the effects of age on BNM and VS connectivities. BNM connectivity to the visual and somatomotor cortices decreases while connectivity to subcortical structures including the midbrain, thalamus, and pallidum increases with age. These findings of age-related changes of cerebral functional connectivity of the BNM may facilitate research of the neural bases of cognitive decline in health and illness.


Subject(s)
Aging/physiology , Basal Nucleus of Meynert/anatomy & histology , Basal Nucleus of Meynert/physiology , Neostriatum/anatomy & histology , Neostriatum/physiology , Neural Pathways/anatomy & histology , Neural Pathways/physiology , Adolescent , Adult , Basal Nucleus of Meynert/growth & development , Female , Head Movements , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Neostriatum/growth & development , Neural Pathways/growth & development , Rest/physiology , Sex Characteristics , Young Adult
14.
J Neurochem ; 127(3): 365-77, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23957451

ABSTRACT

In this study, we have evaluated cerebral atrophy, neurometabolite homeostasis, and neural energetics in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) model of Parkinson's disease. In addition, the efficacy of acute l-DOPA treatment for the reversal of altered metabolic functions was also evaluated. Cerebral atrophy and neurochemical profile were monitored in vivo using MRI and (1) H MR Spectroscopy. Cerebral energetics was studied by (1) H-[(13) C]-NMR spectroscopy in conjunction with infusion of (13) C labeled [1,6(-13) C2 ]glucose or [2-(13) C]acetate. MPTP treatment led to reduction in paw grip strength and increased level of GABA and myo-inositol in striatum and olfactory bulb. (13) C Labeling of glutamate-C4 (1.93 ± 0.24 vs. 1.48 ± 0.06 µmol/g), GABA-C2 (0.24 ± 0.04 vs. 0.18 ± 0.02 µmol/g) and glutamaine-C4 (0.26 ± 0.04 vs. 0.20 ± 0.04 µmol/g) from [1,6-(13) C2 ]glucose was found to be decreased with MPTP exposure in striatum as well as in other brain regions. However, glutamine-C4 labeling from [2-(13) C]acetate was found to be increased in the striatum of the MPTP-treated mice. Acute l-DOPA treatment failed to normalize the increased ventricular size and level of metabolites but recovered the paw grip strength and (13) C labeling of amino acids from [1,6-(13) C2 ]glucose and [2-(13) C]acetate in MPTP-treated mice. These data indicate that brain energy metabolism is impaired in Parkinson's disease and acute l-DOPA therapy could temporarily recover the cerebral metabolism. Cerebral atrophy, neurometabolite homeostasis, and neural energetics have been evaluated in an MPTP model of Parkinson's disease using MRI, in vivo (1) H MRS and (1) H-[(13) C]-NMR spectroscopy, respectively. MPTP treatment led to reduced paw grip strength and neuronal function. Acute Levodopa treatment was able to recover the diminished motor function and cerebral function. CMRGlc, Cerebral metabolic rate of glucose oxidation; MPTP, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridin.


Subject(s)
Antiparkinson Agents/therapeutic use , Brain Chemistry/physiology , Energy Metabolism/physiology , Levodopa/therapeutic use , MPTP Poisoning/drug therapy , MPTP Poisoning/metabolism , Parkinson Disease, Secondary/drug therapy , Parkinson Disease, Secondary/metabolism , Acetates/metabolism , Algorithms , Animals , Blood Glucose/metabolism , Brain Chemistry/drug effects , Energy Metabolism/drug effects , Glutamates/physiology , Hand Strength/physiology , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred C57BL , Neostriatum/anatomy & histology , Neostriatum/metabolism , Oxidation-Reduction , Parkinson Disease, Secondary/chemically induced , Psychomotor Performance/physiology , Radiopharmaceuticals/pharmacokinetics
15.
Brain Struct Funct ; 218(3): 697-709, 2013 May.
Article in English | MEDLINE | ID: mdl-22576749

ABSTRACT

The caudate and putamen nuclei have been traditionally divided into dorsal and ventral territories based on their segregated patterns of functional and anatomical connectivity with distributed cortical regions. Activity-dependent structural plasticity may potentially lead to the development of regional volume correlations, or structural covariance, between the different components of each cortico-striatal circuit. Here, we studied the whole-brain structural covariance patterns of four neostriatal regions belonging to distinct cortico-striatal circuits. We also assessed the potential modulating influence of laterality, age and gender. T1-weighted three-dimensional magnetic resonance images were obtained from ninety healthy participants (50 females). Following data pre-processing, the mean signal value per hemisphere was calculated for the 'seed' regions of interest, located in the dorsal and ventral caudate and the dorsal-caudal and ventral-rostral putamen. Statistical parametric mapping was used to estimate whole-brain voxel-wise structural covariance patterns for each striatal region, controlling for the shared anatomical variance between regions in order to obtain maximally specific structural covariance patterns. As predicted, segregated covariance patterns were observed. Age was found to be a relevant modulator of the covariance patterns of the right caudate regions, while laterality effects were observed for the dorsal-caudal putamen. Gender effects were only observed via an interaction with age. The different patterns of structural covariance are discussed in detail, as well as their similarities with the functional and anatomical connectivity patterns reported for the same striatal regions in other studies. Finally, the potential mechanisms underpinning the phenomenon of volume correlations between distant cortico-striatal structures are also discussed.


Subject(s)
Brain Mapping , Neostriatum/anatomy & histology , Neural Pathways/anatomy & histology , Adult , Age Factors , Female , Functional Laterality , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Putamen , Sex Factors , Statistics as Topic , Young Adult
16.
Hum Brain Mapp ; 34(2): 327-46, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23169482

ABSTRACT

Water diffusion magnetic resonance imaging (dMRI) is a powerful tool for studying biological tissue microarchitectures in vivo. Recently, there has been increased effort to develop quantitative dMRI methods to probe both length scale and orientation information in diffusion media. Diffusion spectrum imaging (DSI) is one such approach that aims to resolve such information based on the three-dimensional diffusion propagator at each voxel. However, in practice, only the orientation component of the propagator function is preserved when deriving the orientation distribution function. Here, we demonstrate how a straightforward extension of the linear spherical deconvolution (SD) model can be used to probe tissue orientation structures over a range (or "spectrum") of length scales with minimal assumptions on the underlying microarchitecture. Using high b-value Cartesian q-space data on a rat brain tissue sample, we demonstrate how this "restriction spectrum imaging" (RSI) model allows for separating the volume fraction and orientation distribution of hindered and restricted diffusion, which we argue stems primarily from diffusion in the extraneurite and intraneurite water compartment, respectively. Moreover, we demonstrate how empirical RSI estimates of the neurite orientation distribution and volume fraction capture important additional structure not afforded by traditional DSI or fixed-scale SD-like reconstructions, particularly in gray matter. We conclude that incorporating length scale information in geometric models of diffusion offers promise for advancing state-of-the-art dMRI methods beyond white matter into gray matter structures while allowing more detailed quantitative characterization of water compartmentalization and histoarchitecture of healthy and diseased tissue.


Subject(s)
Brain/anatomy & histology , Diffusion Tensor Imaging/methods , Algorithms , Animals , Axons/physiology , Body Water/physiology , Brain Mapping , Cell Membrane/physiology , Cerebellum/anatomy & histology , Cerebellum/cytology , Cerebral Cortex/anatomy & histology , Cerebral Cortex/cytology , Corpus Callosum/physiology , Diffusion Tensor Imaging/instrumentation , Globus Pallidus/anatomy & histology , Globus Pallidus/cytology , Image Processing, Computer-Assisted , Models, Anatomic , Monte Carlo Method , Neostriatum/anatomy & histology , Neostriatum/cytology , Neurites/physiology , Neurites/ultrastructure , Rats , Rats, Sprague-Dawley , Signal Processing, Computer-Assisted
17.
Neuroscience ; 226: 145-55, 2012 Dec 13.
Article in English | MEDLINE | ID: mdl-23000621

ABSTRACT

The phosphodiesterases (PDEs) are a superfamily of enzymes that regulate spatio-temporal signaling by the intracellular second messengers cAMP and cGMP. PDE2A is expressed at high levels in the mammalian brain. To advance our understanding of the role of this enzyme in regulation of neuronal signaling, we here describe the distribution of PDE2A in the rat brain. PDE2A mRNA was prominently expressed in glutamatergic pyramidal cells in cortex, and in pyramidal and dentate granule cells in the hippocampus. Protein concentrated in the axons and nerve terminals of these neurons; staining was markedly weaker in the cell bodies and proximal dendrites. In addition, in both hippocampus and cortex, small populations of non-pyramidal cells, presumed to be interneurons, were strongly immunoreactive. PDE2A mRNA was expressed in medium spiny neurons in neostriatum. Little immunoreactivity was observed in cell bodies, whereas dense immunoreactivity was found in the axon tracts of these neurons and their terminal regions in globus pallidus and substantia nigra pars reticulata. Immunostaining was dense in the medial habenula, but weak in other diencephalic regions. In midbrain and hindbrain, immunostaining was restricted to discrete regions of the neuropil or clusters of cell bodies. These results suggest that PDE2A may modulate cortical, hippocampal and striatal networks at several levels. Preferential distribution of PDE2A into axons and terminals of the principal neurons suggests roles in regulation of axonal excitability or transmitter release. The enzyme is also in forebrain interneurons, and in mid- and hindbrain neurons that may modulate forebrain networks and circuits.


Subject(s)
Brain/enzymology , Cyclic Nucleotide Phosphodiesterases, Type 2/metabolism , Animals , Antisense Elements (Genetics) , Autoradiography , Blood Vessels/enzymology , Brain/anatomy & histology , Brain Mapping , Cerebral Cortex/anatomy & histology , Cerebral Cortex/enzymology , Dendrites/enzymology , Fluorescent Antibody Technique , Hippocampus/anatomy & histology , Hippocampus/enzymology , Immunoenzyme Techniques , Immunohistochemistry , In Situ Hybridization , Neostriatum/anatomy & histology , Neostriatum/enzymology , Neurons/enzymology , Pyramidal Cells/enzymology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Spinal Cord/enzymology
18.
PLoS One ; 7(1): e29517, 2012.
Article in English | MEDLINE | ID: mdl-22235303

ABSTRACT

Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI) to investigate the functional and structural organization of the human (pre)frontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation. We observed several bilateral functional subdivisions along the precentral sulcus around the human frontal eye fields (FEF): a medial and lateral zone activating for saccades in darkness, a more fronto-medial zone preferentially active for ipsilateral antisaccades, and a large anterior strip along the precentral sulcus activating for visual stimulus presentation during fixation. The supplementary eye fields (SEF) were identified along the medial wall containing all aforementioned functions. In the striatum, the BG area receiving almost all cortical input, all saccade related activation was observed in the putamen, previously considered a skeletomotor striatal subdivision. Activation elicited by the cue instructing pro or antisaccade trials was clearest in the medial FEF and right putamen. DTI fiber tracking revealed that the subdivisions of the human FEF complex are mainly connected to the putamen, in agreement with the fMRI findings. The present findings demonstrate that the human FEF has functional subdivisions somewhat comparable to non-human primates. However, the connections to and activation in the human striatum preferentially involve the putamen, not the caudate nucleus as is reported for monkeys. This could imply that fronto-striatal projections for the oculomotor system are fundamentally different between humans and monkeys. Alternatively, there could be a bias in published reports of monkey studies favoring the caudate nucleus over the putamen in the search for oculomotor functions.


Subject(s)
Basal Ganglia/physiology , Brain Mapping/methods , Diffusion Tensor Imaging/methods , Nerve Net/physiology , Prefrontal Cortex/physiology , Saccades/physiology , Volition/physiology , Adult , Basal Ganglia/anatomy & histology , Female , Humans , Male , Neostriatum/anatomy & histology , Neostriatum/physiology , Nerve Net/anatomy & histology , Prefrontal Cortex/anatomy & histology , Young Adult
19.
Neuroimage ; 58(4): 1090-100, 2011 Oct 15.
Article in English | MEDLINE | ID: mdl-21791247

ABSTRACT

The corticospinal tracts and the basal ganglia continue to develop during childhood and adolescence, and indices of their maturation can be obtained using diffusion-weighted imaging. Here we show that a simple measure of visuomotor function is correlated with diffusion parameters in the corticospinal tracts and neostriatum. In a cohort of 75 typically-developing children aged 7 to 13years, mean 5-choice reaction times (RTs) were assessed. We hypothesised that children with faster choice RTs would show lower mean diffusivity (MD) in the corticospinal tracts and neostriatum and higher fractional anisotropy (FA) in the corticospinal tracts, after controlling for age, gender, and handedness. Mean MD and/or FA were extracted from the right and left corticospinal tracts, putamen, and caudate nuclei. As predicted, faster 5-choice RTs were associated with lower MD in the corticospinal tracts, putamen, and caudate. MD effects on RT were bilateral in the corticospinal tracts and putamen, whilst right caudate MD was more strongly related to performance than was left caudate MD. Our results suggest a link between motor performance variability in children and diffusivity in the motor system, which may be related to: individual differences in the phase of fibre tract and neostriatal maturation in children of similar age, individual differences in motor experience during childhood (i.e., use-dependent plasticity), and/or more stable individual differences in the architecture of the motor system.


Subject(s)
Brain/anatomy & histology , Brain/physiology , Choice Behavior/physiology , Reaction Time/physiology , Space Perception/physiology , Visual Perception/physiology , Adolescent , Anisotropy , Child , Diffusion Magnetic Resonance Imaging , Female , Humans , Image Processing, Computer-Assisted , Male , Movement/physiology , Neostriatum/anatomy & histology , Neostriatum/physiology , Neural Pathways/physiology , Psychomotor Performance/physiology , Pyramidal Tracts/physiology
20.
J Biomed Sci ; 18: 34, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21631922

ABSTRACT

BACKGROUND: Mu opioid receptor (MOR), which plays key roles in analgesia and also has effects on learning and memory, was reported to distribute abundantly in the patches of the neostriatum. The marginal division (MrD) of the neostriatum, which located at the caudomedial border of the neostriatum, was found to stain for enkephalin and substance P immunoreactivities and this region was found to be involved in learning and memory in our previous study. However, whether MOR also exists in the MrD has not yet been determined. METHODS: In this study, we used western blot analysis and immunoperoxidase histochemical methods with glucose oxidase-DAB-nickel staining to investigate the expression of MOR in the MrD by comparison to the patches in the neostriatum. RESULTS: The results from western blot analyses revealed that the antibody to MOR detected a 53 kDa protein band, which corresponded directly to the molecular weight of MOR. Immunohistochemical results showed that punctate MOR-immunoreacted fibers were observed in the "patch" areas in the rostrodorsal part of the neostriatum but these previous studies showed neither labelled neuronal cell bodies, nor were they shown in the caudal part of the neostriatum. Dorsoventrally oriented dark MOR-immunoreactive nerve fibers with individual labelled fusiform cell bodies were firstly observed in the band at the caudomedial border, the MrD, of the neostriatum. The location of the MOR-immunoreactivity was in the caudomedial border of the neostriatum. The morphology of the labelled fusiform neuronal somatas and the dorsoventrally oriented MOR-immunoreacted fibers in the MrD was distinct from the punctate MOR-immunoreactive diffuse mosaic-patterned patches in the neostriatum. CONCLUSIONS: The results indicated that MOR was expressed in the MrD as well as in patches in the neostriatum of the rat brain, but with different morphological characteristics. The punctate MOR-immunoreactive and diffuse mosaic-patterned patches were located in the rostrodorsal part of the neostriatum. By contrast, in the MrD, the dorsoventrally parallel oriented MOR-immunoreactive fibers with individual labelled fusiform neuronal somatas were densely packed in the caudomedial border of the neostriatum. The morphological difference in MOR immunoreactivity between the MrD and the patches indicated potential functional differences between them. The MOR most likely plays a role in learning and memory associated functions of the MrD.


Subject(s)
Neostriatum/metabolism , Receptors, Opioid, mu/metabolism , Animals , Blotting, Western , Immunoenzyme Techniques , Learning , Male , Memory , Neostriatum/anatomy & histology , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu/physiology
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