Background
The development and maintenance of alcohol use disorders (AUD) have been hypothesized to be associated with an imbalance of glutamate (GLU) homeostasis. White matter (WM) loss, especially ...in anterior brain regions, has been reported in alcohol dependence, which may involve disturbances in both myelin and axonal integrity. Frontal lobe dysfunction plays an important role in addiction, because it is suggested to be associated with the loss of control over substance use. This study investigated magnetic resonance spectroscopy (MRS)‐detectable Glu levels in frontal WM of non‐treatment‐seeking heavy drinkers and its associations with AUD symptoms.
Methods
Single‐voxel MR spectra optimized for Glu assessment (TE 80 ms) were acquired at 3T from a frontal WM voxel in a group of heavy drinking, non‐treatment‐seeking subjects in comparison with a group of subjects with only light alcohol consumption.
Results
The results corroborate previous findings of increased total choline in heavy drinking subjects. A negative association of Glu levels with severity of alcohol dependence and especially loss of control over time and amount of alcohol intake was observed.
Conclusions
In contrast to the rather unspecific rise in choline‐containing compounds, low Glu in frontal WM may be specific for the shift from nondependent heavy drinking to dependence and does not reflect a simple effect of the amount of alcohol consumption alone.
Cocaine addiction is a multi‐dimensional behavioral disorder characterized by a loss of control over cocaine taking despite of detrimental consequences. Structural MRI studies have revealed ...association between cocaine consumption and gray matter volume (GMV) in cocaine‐addicted patients. However, the behavioral correlates of GMV in cocaine addiction are poorly understood. Here, we used a DSM‐IV‐based rat model of cocaine addiction with high face validity for structural imaging. According to three behavioral sub‐dimensions of addiction, rats were separated into two groups showing either addict‐like or non‐addict‐like behavior. These behavioral sub‐dimensions were (1) the inability to refrain from drug‐seeking and taking, (2) high motivation for the drug, and (3) maintained drug use despite negative consequences. In these rats, we performed structural MRI with voxel‐based morphometry and analyzed the interaction of GMV with behavioral sub‐dimensions in cocaine‐addicted rats. Our major findings are that GMV differentially correlate with the inability to refrain from drug‐seeking and taking in addict‐like and non‐addict‐like rats within the somatosensory cortices and the amygdala. High motivation for the drug differentially correlates with GMV in addict‐like and non‐addict‐like rats within the medial prefrontal cortex, and maintained drug use despite negative consequences differentially correlates with GMV in these two groups of rats within the periaqueductal gray. Our results demonstrate that the behavioral differences characterizing addict‐like and non‐addict‐like rats in each behavioral sub‐dimension of addiction are reflected by divergent covariance with GMV. We conclude that structural imaging provides specific neuroanatomical correlates of behavioral sub‐dimensions of addiction.
Enhanced somatosensory and insular cortex gray matter volume (GMV) predicts perseverance in cocaine seeking. Lower medial prefontal cortex GMV predicts enhanced motivation for cocaine. Lower PAG periaqueductal gray GMV predicts enhanced compulsivity in addicted rats.
Background
Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal‐associated changes in ...glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats.
Methods
Alcohol‐dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol‐exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence.
Results
In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N‐acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model.
Conclusions
Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal‐induced hyperglutamatergic neurotoxicity, alcohol‐induced neural changes, and training‐associated effects of abstinence on hippocampal tissue integrity.
Associations of higher markers of glutamatergic metabolism with lower hippocampal volumes after alcohol withdrawal were revealed by MR spectroscopy and MR imaging in alcohol dependent patients and in an animal model that was designed to parallel the patient situation. In both species, reductions in N‐acetylaspartate – a marker of neuronal integrity – recovered quickly after alcohol withdrawal unless a severe withdrawal syndrome occurred. Results are discussed in light of the glutamate hypothesis of alcoholism and possible alternatives.
Abstract Social recognition is essential for the formation of social structures. Many times, recognition comes with lesser exploration of familiar animals. This lesser exploration has led to the ...assumption that recognition may be a habituation memory. The underlying memory mechanisms and the thereby acquired cortical representations of familiar mice have remained largely unknown, however. Here, we introduce an approach directly examining the recognition process from volatile body odors among male mice. We show that volatile body odors emitted by mice are sufficient to identify individuals and that more salience is assigned to familiar mice. Familiarity is encoded by reinforced population responses in two olfactory cortex hubs and communicated to other brain regions. The underlying oxytocin-induced plasticity promotes the separation of the cortical representations of familiar from other mice. In summary, neuronal encoding of familiar animals is distinct and utilizes the cortical representational space more broadly, promoting storage of complex social relationships.
Magnetic resonance imaging (MRI) of the brain combined with voxel-based morphometry (VBM) revealed changes in gray matter volume (GMV) in various disorders. However, the cellular basis of GMV changes ...has remained largely unclear. We correlated changes in GMV with cellular metrics by imaging mice with MRI and two-photon in vivo microscopy at three time points within 12 weeks, taking advantage of age-dependent changes in brain structure. Imaging fluorescent cell nuclei allowed inferences on (i) physical tissue volume as determined from reference spaces outlined by nuclei, (ii) cell density, (iii) the extent of cell clustering, and (iv) the volume of cell nuclei. Our data indicate that physical tissue volume alterations only account for 13.0% of the variance in GMV change. However, when including comprehensive measurements of nucleus volume and cell density, 35.6% of the GMV variance could be explained, highlighting the influence of distinct cellular mechanisms on VBM results.
Recently, a larger hippocampus was found in exercising mice and men. Here we studied the morphological underpinnings in wheel running mice by longitudinal magnetic resonance imaging. Voxel-based ...morphometry revealed that running increases hippocampal volume by inhibiting an early age-related gray matter loss. Disruption of neurogenesis-related neuroplasticity by focalized irradiation is sufficient to block positive effects of exercise on macroscopic brain morphology.
The utilization of magnetic resonance imaging (MRI) methods in rodent models of psychiatric disorders provides considerable benefits for the identification of disease-associated brain circuits and ...metabolic changes. In this review, we discuss advantages and challenges of animal MRI and provide an overview of the major structural (voxel-based morphometry and diffusion tensor imaging) and functional approaches resting-state functional MRI (rs-fMRI), MR spectroscopy (MRS), regional cerebral blood volume measurement and arterial spin labelling that are applied in animal MRI research. The review mainly focuses on rs-fMRI and MRS. Finally, we take a look at some recent developments and refinements in the field.
Rationale
Aberrant prefrontal-hippocampal (PFC-HC) connectivity is disrupted in several psychiatric and at-risk conditions. Advances in rodent functional imaging have opened the possibility that this ...phenotype could serve as a translational imaging marker for psychiatric research. Recent evidence from functional magnetic resonance imaging (fMRI) studies has indicated an increase in PFC-HC coupling during working-memory tasks in both schizophrenic patients and at-risk populations, in contrast to a decrease in resting-state PFC-HC connectivity. Acute ketamine challenge is widely used in both humans and rats as a pharmacological model to study the mechanisms of
N
-methyl-
d
-aspartate (NMDA) receptor hypofunction in the context of psychiatric disorders.
Objectives
We aimed to establish whether acute ketamine challenge has consistent effects in rats and humans by investigating resting-state fMRI PFC-HC connectivity and thus to corroborate its potential utility as a translational probe.
Methods
Twenty-four healthy human subjects (12 females, mean age 25 years) received intravenous doses of either saline (placebo) or ketamine (0.5 mg/kg body weight). Eighteen Sprague-Dawley male rats received either saline or ketamine (25 mg/kg). Resting-state fMRI measurements took place after injections, and the data were analyzed for PFC-HC functional connectivity.
Results
In both species, ketamine induced a robust increase in PFC-HC coupling, in contrast to findings in chronic schizophrenia.
Conclusions
This translational comparison demonstrates a cross-species consistency in pharmacological effect and elucidates ketamine-induced alterations in PFC-HC coupling, a phenotype often disrupted in pathological conditions, which may give clue to understanding of psychiatric disorders and their onset, and help in the development of new treatments.
Voluntary exercise has tremendous effects on adult hippocampal plasticity and metabolism and thus sculpts the hippocampal structure of mammals. High-field 1H magnetic resonance (MR) investigations at ...9.4T of metabolic and structural changes can be performed non-invasively in the living rodent brain. Numerous molecular and cellular mechanisms mediating the effects of exercise on brain plasticity and behavior have been detected in vitro. However, in vivo attempts have been rare. In this work a method for voxel based morphometry (VBM) was developed with automatic tissue segmentation in mice using a 9.4T animal scanner equipped with a 1H-cryogenic coil. The thus increased signal to noise ratio enabled the acquisition of high resolution T2-weighted images of the mouse brain in vivo and the creation of group specific tissue class maps for the segmentation and normalization with SPM. The method was used together with hippocampal single voxel 1H MR spectroscopy to assess the structural and metabolic differences in the mouse brain due to voluntary wheel running. A specific increase of hippocampal volume with a concomitant decrease of hippocampal glutamate levels in voluntary running mice was observed. An inverse correlation of hippocampal gray matter volume and glutamate concentration indicates a possible implication of the glutamatergic system for hippocampal volume.
► Development of a fully automatic segmentation for in vivo mouse 3D data. ► Combination of 1H MRS VBM and spectroscopy in voluntary exercising and sedentary mice. ► Increase of hippocampal volume after voluntary wheel running detected with VBM. ► Decrease of spectroscopic glutamate concentrations in the hippocampus of running mice. ► Negative correlation between hippocampal glutamate concentrations and volume.
Identifying the circuits responsible for cognition and understanding their embedded computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach, from ...behavioral modeling and fMRI in task-performing mice to cellular recordings, in order to disentangle local network contributions to olfactory reinforcement learning. At mesoscale, fMRI identifies a functional olfactory-striatal network interacting dynamically with higher-order cortices. While primary olfactory cortices respectively contribute only some value components, the downstream olfactory tubercle of the ventral striatum expresses comprehensively reward prediction, its dynamic updating, and prediction error components. In the tubercle, recordings reveal two underlying neuronal populations with non-redundant reward prediction coding schemes. One population collectively produces stabilized predictions as distributed activity across neurons; in the other, neurons encode value individually and dynamically integrate the recent history of uncertain outcomes. These findings validate a cross-scale approach to mechanistic investigations of higher cognitive functions in rodents.
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