Thalamus glutamate

The thalamus is a central link between cortical and subcortical brain motor systems. Axons from the deep nuclei of the cerebellum (DCN), or the output nuclei of the basal ganglia system (substantia nigra reticulata, SNr; and internal pallidum GPi/ENT) monosynaptically innervate the thalamus, prominently some nuclei of the ventral nuclear group. In turn, axons from these ventral nuclei innervate the motor and premotor areas of the cortex, where their input is critical for planning, execution and learning of rapid and precise movements...

The medial prefrontal cortex (mPFC) controls behavior via connections with limbic excitatory afferents that engage various inhibitory motifs to shape mPFC circuit function. The dynorphin (Dyn) / kappa-opioid receptor (KOR) system is highly enriched in the mPFC, and its dysregulation is implicated in neuropsychiatric disorders. However, it is unclear how the Dyn / KOR system modulates excitatory and inhibitory circuits that are integral for mPFC information processing and behavioral control. Here, we provide a circuit-based framework wherein mPFC Dyn / KOR signaling regulates excitation-inhibition balance by toggling which afferents drive mPFC neurons...

Craving is a core symptom of cocaine use disorder and a major factor for relapse risk. To date, there is no pharmacological therapy to treat this disease or at least to alleviate cocaine craving as a core symptom. In animal models, impaired prefrontal-striatal signalling leading to altered glutamate release in the nucleus accumbens appear to be the prerequisite for cocaine-seeking. Thus, those network and metabolic changes may constitute the underlying mechanisms for cocaine craving and provide a potential treatment target...

INTRODUCTION: Ketamine, a glutamate NMDA receptor antagonist, is suggested to act very rapidly and durably on the depressive symptoms including treatment-resistant patients but its mechanisms of action remain unclear. There is a requirement for non-invasive biomarkers, such as imaging techniques, which hold promise in monitoring and elucidating its therapeutic impact. METHODS: We explored the glucose metabolism with [18 F]FDG positron emission tomography (PET) in ten male rats in a longitudinal study designed to compare imaging patterns immediately after acute subanaesthetic ketamine injection (i...

BACKGROUND: Disturbances in presynaptic dopamine activity and levels of GABA (gamma-aminobutyric acid) and glutamate plus glutamine collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsychotic-naïve patients with first-episode psychosis from healthy control subjects. METHODS: We included 23 patients (mean age 22...

The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon, is functionally implicated in the basal ganglia circuits. Because of this strict structural and functional relationship with the circuits of the basal ganglia, the STh is a current target for deep brain stimulation, a neurosurgical procedure employed to alleviate symptoms in movement disorders, such as Parkinson's disease and dystonia. However, despite the great relevance of this structure for both basal ganglia physiology and pathology, the neurochemical and molecular anatomy of the STh remains largely unknown...

The anterior and posterior subregions of the paraventricular thalamus (aPVT and pPVT, respectively) play unique roles in learned behaviors, from fear conditioning to alcohol/drug intake, potentially through differentially organized projections to limbic brain regions including the nucleus accumbens medial shell (mNAcSh). Here, we found that the aPVT projects broadly to the mNAcSh and that the aPVT-mNAcSh circuit encodes positive valence, such that in vivo manipulations of the circuit modulated both innately programmed and learned behavioral responses to positively and negatively valenced stimuli, particularly in females...

Real-time monitoring of various neurochemicals with high spatial resolution in multiple brain regions in vivo can elucidate neural circuits related to various brain diseases. However, previous systems for monitoring neurochemicals have limitations in observing multiple neurochemicals without crosstalk in real time, and these methods cannot record electrical activity, which is essential for investigating neural circuits. Here, we present a real-time bimodal (RTBM) neural probe that uses monolithically integrated biosensors and multiple shanks to study the connectivity of neural circuits by measuring multiple neurochemicals and electrical neural activity in real time...

Proton magnetic resonance spectroscopy (1 H-MRS) is an advanced method of examining metabolic profiles. The present study aimed to assess in vivo metabolite levels in areas of normal-appearing grey (thalamus) and white matter (centrum semiovale) using 1 H-MRS in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis and compare them to healthy controls (HCs). Data from 35 patients with CIS (CIS group), of which 23 were untreated (CIS-untreated group) and 12 were treated (CIS-treated group) with disease-modifying-therapies (DMTs) at the time of 1 H-MRS, and from 28 age- and sex-matched HCs were collected using a 3...

BACKGROUND: The glycinergic system plays an important inhibitory role in the mouse central nervous system, where glycine controls the excitability of spinal itch- and pain-mediating neurons. Impairments of the glycine receptors can cause motor and sensory deficits. Glycine exerts inhibition through interaction with ligand-gated ion channels composed of alpha and beta subunits. We have investigated the mRNA expression of the glycine receptor alpha 3 (Glra3) subunit in the nervous system as well as in several peripheral organs of female and male mice...

BACKGROUND: The posterior intralaminar (PIL) complex of the thalamus is a multimodal nucleus that has been implicated in maternal behaviors and conspecific social behaviors in male and female rodents. Glutamatergic neurons are a major component of the PIL; however, their specific activity and role during social interactions has not yet been assessed. METHODS: We used immunohistochemistry for the immediate early gene c-fos as a proxy for neuronal activity in the PIL of mice exposed to a novel social stimulus, a novel object stimulus, or no stimulus...

Cognitive impairment occurs in 40-65% of persons with multiple sclerosis and may be related to alterations in glutamatergic and GABAergic neurotransmission. Therefore, the aim of this study was to determine how glutamatergic and GABAergic changes relate to cognitive functioning in multiple sclerosis in vivo . Sixty persons with multiple sclerosis (mean age 45.5 ± 9.6 years, 48 females, 51 relapsing-remitting multiple sclerosis) and 22 age-matched healthy controls (45.6 ± 22.0 years, 17 females) underwent neuropsychological testing and MRI...

Deconvolution of potential drug targets of the central nervous system (CNS) is particularly challenging because of the complicated structure and function of the brain. Here, a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging. This strategy can map various substances including exogenous drugs, isotopically labeled metabolites, and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways...

OBJECTIVES: To investigate the significance of proton magnetic resonance spectroscopy (1 H-MRS) and glutamate chemical exchange saturation transfer (Glu-CEST) techniques in assessing the condition and prognosis of acute bilirubin encephalopathy patients and to understand the mechanism of nerve injury in this disease. MATERIALS AND METHODS: From September 2019 to February 2021, 31 neonates with acute bilirubin encephalopathy and 16 healthy neonates were enrolled in this study...

The dorsal striatum (DS) mediates the selection of actions for reward acquisition necessary for survival. Striatal pathology contributes to several neuropsychiatric conditions, including aberrant selection of actions for specific rewards in addiction. A major source of glutamate driving striatal activity is the rostral intralaminar nuclei (rILN) of the thalamus. Yet, the information that is relayed to the striatum to support action selection is unknown. Here, we discovered that rILN neurons projecting to the DS are innervated by a range of cortical and subcortical afferents and that rILN→DS neurons stably signaled at two time points in mice performing an action sequence task reinforced by sucrose reward: action initiation and reward acquisition...

Great progress has been made in understanding the neural mechanisms associated with alcohol-dependent (AD) patients. However, the interactions within the reward circuits of the patients need further exploration. Glutamatergic projections from the prefrontal cortex to some brain regions are present in the reward circuit. However, little is known about the potential implications of glutamate levels in the prefrontal cortex on abnormal interactions within reward circuits in AD patients. To determine the potential roles of reward circuits in drinking, we investigated differences in resting-state functional connectivity (RSFC) and multivariate Granger causality analysis between 20 AD patients and 20 healthy controls (HC)...

BACKGROUND: Aberrant anticipation of motivational salient events and processing of outcome evaluation in striatal and prefrontal regions have been suggested to underlie psychosis. Altered glutamate levels have likewise been linked to schizophrenia. Glutamatergic abnormalities may affect the processing of motivational salience and outcome evaluation. It remains unresolved, whether glutamatergic dysfunction is associated with the coding of motivational salience and outcome evaluation in antipsychotic-naïve patients with first-episode psychosis...

To identify central metabolites and peripheral measures associated with neuroinflammation in fibromyalgia (FM), we scanned [11C]-(R)-PK11195 positron emission tomography and magnetic resonance spectroscopy in FM patients. We measured associations between neurometabolite levels measured by magnetic resonance spectroscopy and the extent of neuroinflammation inferred by the distribution volume ratios of [11C]-(R)-PK11195 positron emission tomography in 12 FM patients and 13 healthy controls. We also examined the associations between peripheral parameters, such as creatinine and C-reactive protein, and neuroinflammation...

AIMS: Depression in bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatments and poor clinical outcomes in many bipolar patients. Herein, we report direct comparisons between medication-free patients with BD and those with UD in terms of the microstructure and neurometabolites in eight brain regions. METHODS: A total of 20 patients with BD, 30 with UD patients, and 20 matched healthy controls (HCs) underwent 3.0T magnetic resonance imaging with chemical exchange saturation transfer (CEST) for glutamate (Glu; GluCEST) imaging, multivoxel magnetic resonance spectroscopy, and diffusion kurtosis imaging...

JNJ-42491293 is a metabotropic glutamate 2 (mGlu2 ) positive allosteric modulator (PAM) that was radiolabelled with [11 C]- to serve as a positron emission tomography (PET) ligand. Indeed, in vitro, the molecule displays high selectivity at mGlu2 receptors. However, PET experiments performed in rats, macaques and humans, have suggested that [11 C]-JNJ-42491293 could interact with an unidentified, non-mGlu2 receptor binding site. The brain distribution of [11 C]-JNJ-42491293 has not been determined in the brain of the common marmoset, a small non-human primate increasingly used in neuroscience research...