Role of the caudate-putamen nucleus in sensory gating in induced tinnitus in rats.
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ABSTRACT:
SUBMITTER: Wang ML
PROVIDER: S-EPMC8354105 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVEThe object of this study was to define caudate nucleus locations responsive to intraoperative direct electrical stimulation for tinnitus loudness modulation and relate those locations to functional connectivity maps between caudate nucleus subdivisions and auditory cortex.METHODSSix awake study participants who underwent bilateral deep brain stimulation (DBS) electrode placement in the caudate nucleus as part of a phase I clinical trial were analyzed for tinnitus modulation in response to acute stimulation at 20 locations. Resting-state 3-T functional MRI (fMRI) was used to compare connectivity strength between centroids of tinnitus loudness-reducing or loudness-nonreducing caudate locations and the auditory cortex in the 6 DBS phase I trial participants and 14 other neuroimaging participants with a Tinnitus Functional Index > 50.RESULTSAcute tinnitus loudness reduction was observed at 5 caudate locations, 4 positioned at the body and 1 at the head of the caudate nucleus in normalized Montreal Neurological Institute space. The remaining 15 electrical stimulation interrogations of the caudate head failed to reduce tinnitus loudness. Compared to the caudate head, the body subdivision had stronger functional connectivity to the auditory cortex on fMRI (p < 0.05).CONCLUSIONSAcute tinnitus loudness reduction was more readily achieved by electrical stimulation of the caudate nucleus body. Compared to the caudate head, the caudate body has stronger functional connectivity to the auditory cortex. These first-in-human findings provide insight into the functional anatomy of caudate nucleus subdivisions and may inform future target selection in a basal ganglia-centric neuromodulation approach to treat medically refractory tinnitus.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov).
| S-EPMC6687562 | biostudies-literature
Project description:Day-active tree shrews have a well-developed internal capsule (ic) that clearly separates the caudate nucleus (Cd) and putamen (Pu). The striatum consists of the Cd, ic, Pu, and accumbens nucleus (Acb). Here, we characterized the cytoarchitecture of the striatum and the whole-brain inputs to the Cd, Pu, and Acb in tree shrews by using immunohistochemistry and the retrograde tracer Fluoro-Gold (FG). Our data show the distribution patterns of parvalbumin (PV), nitric oxide synthase (NOS), calretinin (CR), and tyrosine hydroxylase (TH) immunoreactivity in the striatum of tree shrews, which were different from those observed in rats. The Cd and Pu mainly received inputs from the thalamus, motor cortex, somatosensory cortex, subthalamic nucleus, substantia nigra, and other cortical and subcortical regions, whereas the Acb primarily received inputs from the anterior olfactory nucleus, claustrum, infralimbic cortex, thalamus, raphe nucleus, parabrachial nucleus, ventral tegmental area, and so on. The Cd, Pu, and Acb received inputs from different neuronal populations in the ipsilateral (60, 67, and 63 brain regions, respectively) and contralateral (23, 20, and 36 brain regions, respectively) brain hemispheres. Overall, we demonstrate that there are species differences between tree shrews and rats in the density of PV, NOS, CR, and TH immunoreactivity in the striatum. Additionally, we mapped for the first time the distribution of whole-brain input neurons projecting to the striatum of tree shrews with FG injected into the Cd, Pu, and Acb. The similarities and differences in their brain-wide input patterns may provide new insights into the diverse functions of the striatal subregions.
| S-EPMC8593333 | biostudies-literature
Project description:Although several methods have been developed to automatically delineate subcortical gray matter structures from MR images, the accuracy of these algorithms has not been comprehensively examined. Most of earlier studies focused primarily on the hippocampus. Here, we assessed the accuracy of two widely used non-commercial programs (FSL-FIRST and Freesurfer) for segmenting the caudate and putamen. T1-weighted 1 mm3 isotropic resolution MR images were acquired for thirty healthy subjects (15 females). Caudate nucleus and putamen were segmented manually by two independent observers and automatically by FIRST and Freesurfer (v4.5 and v5.3). Utilizing manual labels as reference standard the following measures were studied: Dice coefficient (D), percentage volume difference (PVD), absolute volume difference as well as intraclass correlation coefficient (ICC) for consistency and absolute agreement. For putamen segmentation, FIRST achieved higher D, lower PVD and higher ICC for absolute agreement with manual tracing than either version of Freesurfer. Freesurfer overestimated the putamen, while FIRST was not statistically different from manual tracing. The ICC for consistency with manual tracing was similar between the two methods. For caudate segmentation, FIRST and Freesurfer performed more similarly. In conclusion, Freesurfer and FIRST are not equivalent when comparing to manual tracing. FIRST was superior for putaminal segmentation.
| S-EPMC5445091 | biostudies-literature
Project description:The caudate nucleus (CN) and the putamen (PUT) as parts of the human striatum are distinguished by a marked heterogeneity in functional, anatomical, and neurochemical patterns. Our study aimed to document in detail the regional diversity in the distribution of dopamine (DA), serotonin, γ-aminobuturic acid, and choline acetyltransferase within the CN and PUT. For this purpose we dissected the CN as well as the PUT of 12 post-mortem brains of human subjects with no evidence of neurological and psychiatric disorders (38-81 years old) into about 80 tissue parts. We then investigated rostro-caudal, dorso-ventral, and medio-lateral gradients of these neurotransmitter markers. All parameters revealed higher levels, turnover rates, or activities in the PUT than in the CN. Within the PUT, DA levels increased continuously from rostral to caudal. In contrast, the lowest molar ratio of homovanillic acid to DA, a marker of DA turnover, coincided with highest DA levels in the caudal PUT, the part of the striatum with the highest loss of DA in Parkinson's disease (N. Engl. J. Med., 318, 1988, 876). Highest DA concentrations were found in the most central areas both in the PUT and CN. We observed an age-dependent loss of DA in the PUT and CN that did not correspond to the loss described for Parkinson's disease indicating different mechanisms inducing the deficit of DA. Our data demonstrate a marked heterogeneity in the anatomical distribution of neurotransmitter markers in the human dorsal striatum indicating anatomical and functional diversity within this brain structure.
| S-EPMC7078952 | biostudies-literature
Project description:Food restriction (FR) and obesogenic (OB) diets are known to alter brain dopamine transmission and exert opposite modulatory effects on behavioral responsiveness to psychostimulant drugs of abuse. Mechanisms underlying these diet effects are not fully understood. In this study, we examined diet effects on expression and function of the dopamine transporter (DAT) in caudate-putamen (CPu), nucleus accumbens (NAc), and midbrain regions. Dopamine (DA) uptake by CPu, NAc or midbrain synapto(neuro)somes was measured in vitro with rotating disk electrode voltammetry or with [3 H]DA uptake and was found to correlate with DAT surface expression, assessed by maximal [3 H](-)-2-?-carbomethoxy-3-?-(4-fluorophenyl)tropane binding and surface biotinylation assays. FR and OB diets were both found to decrease DAT activity in CPu with a corresponding decrease in surface expression but had no effects in the NAc and midbrain. Diet treatments also affected sensitivity to insulin-induced enhancement of DA uptake, with FR producing an increase in CPu and NAc, likely mediated by an observed increase in insulin receptor expression, and OB producing a decrease in NAc. The increased expression of insulin receptor in NAc of FR rats was accompanied by increased DA D2 receptor expression, and the decreased DAT expression and function in CPu of OB rats was accompanied by decreased DA D2 receptor expression. These results are discussed as partial mechanistic underpinnings of diet-induced adaptations that contribute to altered behavioral sensitivity to psychostimulants that target the DAT.
| S-EPMC5475276 | biostudies-literature
Project description:In Parkinson's disease (PD), aromatic L-amino acid decarboxylase (AADC) is the rate-limiting enzyme in the conversion of L-DOPA (Sinemet) to dopamine (DA). Previous studies in PD animal models demonstrated that lesion of dopaminergic neurons is associated with profound loss of AADC activity in the striatum, blocking efficient conversion of L-DOPA to DA. Relatively few studies have directly analyzed AADC in PD brains. Thus, the aim of this study was to gain a better understanding of regional changes in AADC activity, DA, serotonin and their monoamine metabolites in the striatum of PD patients and experimentally lesioned animals (rat and MPTP-treated nonhuman primate, NHP). Striatal AADC activity was determined post mortem in neuropathologically confirmed PD subjects, animal models and controls. A regional analysis was performed for striatal AADC activity and monoamine levels in NHP tissue. Interestingly, analysis of putaminal AADC activity revealed that control human striatum contained much less AADC activity than rat and NHP striata. Moreover, a dramatic loss of AADC activity in PD striatum compared to controls was detected. In MPTP-treated NHP, caudate nucleus was almost as greatly affected as putamen, although mean DA turnover was higher in caudate nucleus. Similarly, DA and DA metabolites were dramatically reduced in different regions of PD brains, including caudate nucleus, whereas serotonin was relatively spared. After L-DOPA administration in MPTP-treated NHP, very poor conversion to DA was detected, suggesting that AADC in NHP nigrostriatal fibers is mainly responsible for L-DOPA to DA conversion. These data support further the rationale behind viral gene therapy with AAV2-hAADC to restore AADC levels in putamen and suggest further the advisability of expanding vector delivery to include coverage of anterior putamen and the caudate nucleus.
| S-EPMC5293261 | biostudies-literature
Project description:The aim of this study was to determine if differential solubilization of human CNS proteins would increase the total number of proteins that could be visualized using 2-D gel electrophoresis. Hence, proteins were solubilized into Tris, CHAPS and SB3-10 before separation across a pH 4-7 IEF gradient and a 12-14% SDS polyacrylamide gel, which could be achieved with a run-to-run variation of 35% in spot intensity. Because Western blot analyses suggested proteins could be in more than one detergent fraction, we completed a conservative analyses of our 2-D gels assuming spots that appeared on multiple gels at the same molecular weight and pI were the same protein. These analyses show that we had visualized over 3000 unique protein spots across three 2-D gels generated from each sample of human frontal cortex and caudate-putamen. This represented, at worst, a significant increase in the number of spots visualized in the acidic protein spectrum compared to what has been reported in other studies of human CNS. This study, therefore, supports the proposal that the analysis of the human CNS proteome using 2-D gel electrophoresis, combined with appropriate sample preparation, can be used to expand the studies on the pathologies of neurological and psychiatric diseases.
| S-EPMC3056166 | biostudies-literature
Project description:Adenosine is an endogenous nucleoside that modulates important physiological processes, such as vasodilation, in the central nervous system. A rapid, 2-4 s, mode of adenosine signaling has been recently discovered, but the relationship between this type of adenosine and blood flow change has not been characterized. In this study, adenosine and oxygen changes were simultaneously measured using fast-scan cyclic voltammetry. Oxygen changes occur when there is an increase in local cerebral blood flow and thus are a measure of vasodilation. About 34% of adenosine transients in the rat caudate-putamen are correlated with a subsequent transient change in oxygen. The amount of oxygen was correlated with the concentration of adenosine release and larger adenosine transients (over 0.4 ?M) always had subsequent oxygen changes. The average duration of adenosine and oxygen transients was 3.2 and 3.5 s, respectively. On average, the adenosine release starts and peaks 0.2 s prior to the oxygen. The A2a antagonist, SCH442416, decreased the number of both adenosine and oxygen transient events by about 32%. However, the A1 antagonist, DPCPX, did not significantly affect simultaneous adenosine and oxygen release. The nitric oxide (NO) synthase inhibitor l-NAME also did not affect the concentration or number of adenosine and oxygen release events. These results demonstrate that both adenosine and oxygen release are modulated via A2a receptors. The correlation of transient concentrations, time delay between adenosine and oxygen peaks, and effect of A2a receptors suggests that adenosine modulates blood flow on a rapid, sub-second time scale. Read the Editorial Highlight for this article on page 10.
| S-EPMC5164875 | biostudies-literature
Project description:Morphine binding to opioid receptors, mainly to ? opioid receptor (MOR), induces alterations in intracellular pathways essential to the initial development of addiction. The activation of the dopamine D4 receptor (D4R), which is expressed in the caudate putamen (CPu), mainly counteracts morphine-induced alterations in several molecular networks. These involve transcription factors, adaptive changes of MOR signaling, activation of the nigrostriatal dopamine pathway and behavioural effects, underlining functional D4R/MOR interactions. To shed light on the molecular mechanisms implicated, we evaluated the transcriptome alterations following acute administration of morphine and/or PD168,077 (D4R agonist) using whole-genome microarrays and a linear regression-based differential expression analysis. The results highlight the development of a unique transcriptional signature following the co-administration of both drugs that reflects a countereffect of PD168,077 on morphine effects. A KEGG pathway enrichment analysis using GSEA identified 3 pathways enriched positively in morphine vs control and negatively in morphine?+?PD168,077 vs morphine (Ribosome, Complement and Coagulation Cascades, Systemic Lupus Erythematosus) and 3 pathways with the opposite enrichment pattern (Alzheimer's Disease, Neuroactive Ligand Receptor Interaction, Oxidative Phosphorilation). This work supports the massive D4R/MOR functional integration at the CPu and provides a gateway to further studies on the use of D4R drugs to modulate morphine-induced effects.
| S-EPMC5943359 | biostudies-literature
Project description:Expected reward impacts behavior and neuronal activity in brain areas involved in sensorimotor processes. However, where and how reward signals affect sensorimotor signals is unclear. Here, we show evidence that reward-dependent modulation of behavior depends on normal dopamine transmission in the striatum. Monkeys performed a visually guided saccade task in which expected reward gain was different depending on the position of the target. Saccadic reaction times were reliably shorter on large-reward trials than on small-reward trials. When position-reward contingency was switched, the reaction time difference changed rapidly. Injecting dopamine D1 antagonist into the caudate significantly attenuated the reward-dependent saccadic reaction time changes. Conversely, injecting D2 antagonist into the same region enhanced the reward-dependent changes. These results suggest that reward-dependent changes in saccadic eye movements depend partly on dopaminergic modulation of neuronal activity in the caudate nucleus.
| S-EPMC6675290 | biostudies-literature