Native valve endocarditis caused by Corynebacterium striatum without underlying structural heart disease or indwelling cardiovascular medical devices: a case report.

BACKGROUND: Corynebacterium striatum (C. striatum) is a gram-positive, anaerobic bacillus found both environmentally and in human skin and nasal mucosa flora. It is reportedly the etiologic agent of community-acquired and nosocomial diseases and is significantly associated with bacteremia and medical endovascular devices. This is the rare case of mitral valve native valve endocarditis (NVE) caused by C. striatum occurring in a young adult without underlying structural heart disease or indwelling cardiovascular medical devices successfully treated with multidisciplinary therapy. CASE PRESENTATION: The patient was a 28-year-old female with no medical history. She was transferred our hospital due to sudden onset of vertigo and vomit. A computed tomography on day 2 revealed the hydrocephalus due to the cerebellar infarction, and she underwent posterior fossa decompression for cerebellar infarction. An angiography on day 8 revealed a left vertebral artery dissection, which was suspected be the etiology. Afterwards, a sudden fever of 39 degrees developed on day 38. She was diagnosed with aspiration pneumonia and treated with ampicillin/sulbactam but was still febrile at the time of transfer for rehabilitation. Treatment continued with levofloxacin, the patient had no fever decline, and she was readmitted to our hospital. Readmission blood cultures (3/3 sets) revealed C. striatum, and an echocardiogram revealed an 11 mm long mitral valve vegetation, leading to NVE diagnosis. On the sixth illness day, cardiac failure symptoms manifested. Echocardiography revealed mitral valve rupture. She was transferred again on the 11th day of illness, during which time her mitral valve was replaced. C. striatum was detected in the vegetation. Following surgery, she returned to our hospital, and vancomycin administration continued. The patient was discharged after 31 total days of postoperative antimicrobial therapy. The patient experienced no exacerbations thereafter. CONCLUSIONS: We report the rare case of C. striatum mitral valve NVE in a young adult without structural heart disease or indwelling cardiovascular devices. CLINICAL TRIAL NUMBER: Not applicable.

Social reward and nonsocial reward processing across the adult lifespan: An interim multi-echo fMRI and diffusion dataset.

Social relationships change across the lifespan as social networks narrow and motivational priorities shift. These changes may affect, or reflect, differences in how older adults make decisions related to processing social and non-social rewards. While we have shown initial evidence that older adults have a blunted response to some features of social reward, further work in larger samples is needed to replicate our results and probe the extent to which age-related differences translate to real world consequences, such as financial exploitation. To address this gap, we are conducting a 5-year study funded by the National Institute on Aging (NIH R01-AG067011). Over the course of the funding period (2021-2026), this study seeks to: 1) characterize neural responses to social rewards across adulthood; 2) relate those responses to risk for financial exploitation and sociodemographic factors tied to risk; and 3) examine changes in risk for financial exploitation over time in healthy and vulnerable groups of older adults. This paper describes the preliminary release of data for the larger study. Adults (N = 114; 40 male / 70 female / 4 other or non-binary; 21-80 years of age M = 42.78, SD = 17.13) were recruited from the community to undergo multi-echo fMRI while completing tasks that measure brain function during social reward and decision making. Tasks probe neural response to social reward (e.g., peer vs. monetary feedback) and social context and closeness (e.g., sharing a monetary reward with a friend compared to a stranger). Neural response to social decision making is probed via economic trust and ultimatum games. Functional data are complimented by a T1 weighted anatomical scan and multi-shell diffusion-weighted imaging (DWI) to enable tractography and assess neurite orientation dispersion and density. Overall, this dataset has extensive potential for re-use, including leveraging multimodal neuroimaging data, within subject measures of fMRI data from different tasks - data features that are rarely seen in an adult lifespan dataset. Finally, the functional data will allow for developmentally sensitive cross-sectional analyses of differences in brain response to nuanced differences in reward contexts and outcomes (e.g., monetary vs. social; sharing winnings with a friend vs. stranger; stranger vs. computer).

Functional correlation between cerebellum and basal ganglia: A parkinsonism model.

INTRODUCTION: The cerebellar response has been studied for years with different models of alteration of other brain structures to understand its complex functioning and its relationship with the rest of the body. Studies in patients with Parkinson's disease (PD) showed that the cerebellar function is modified by deficit of the basal ganglia; which supports the hypothesis that both structures are related anatomically and functionally. METHODS: In our study, the ventrolateral striatum (VLS) of the basal ganglia was altered by an electrolytic lesion, in order to produce a similar jaw frequency of jaw tremor movements presented in parkinsonism, thereafter we analyzed the effect of the lesion on the expression of multiunit activity (MUA) of the cerebellum. RESULTS: We found cerebellar activation during mandibular movements and increment during oral jaw tremor movements. In addition, the amplitude of baseline MUA registered in animals with alteration of the VLS decreased with respect to the intact group. CONCLUSIONS: Accordingly, we conclude that cerebellar changes in MUA may be due to a decrease in the cerebellar inflectional or as a possible compensatory function between cerebellum and basal ganglia.

Increased GluK1 Subunit Receptors in Corticostriatal Projection from the Anterior Cingulate Cortex Contributed to Seizure-Like Activities.

The corticostriatal connection plays a crucial role in cognitive, emotional, and motor control. However, the specific roles and synaptic transmissions of corticostriatal connection are less studied, especially the corticostriatal transmission from the anterior cingulate cortex (ACC). Here, a direct glutamatergic excitatory synaptic transmission in the corticostriatal projection from the ACC is found. Kainate receptors (KAR)-mediated synaptic transmission is increased in this corticostriatal connection both in vitro and in vivo seizure-like activities. GluK1 containing KARs and downstream calcium-stimulated adenylyl cyclase subtype 1 (AC1) are involved in the upregulation of KARs following seizure-like activities. Inhibiting the activities of ACC or its corticostriatal connection significantly attenuated pentylenetetrazole (PTZ)-induced seizure. Additionally, injection of GluK1 receptor antagonist UBP310 or the AC1 inhibitor NB001 both show antiepileptic effects. The studies provide direct evidence that KARs are involved in seizure activity in the corticostriatal connection and the KAR-AC1 signaling pathway is a potential novel antiepileptic strategy.

Changed ventral striatum structural covariance and grey matter volume in depression during a one-year follow-up.

Empirical findings suggest reduced cortico-striatal structural connectivity in patients with major depressive disorder (MDD). However, the relationship between the abnormal structural covariance and one-year outcome of first-episode drug-naive patients has not been evaluated. This longitudinal study aimed to identify specific changes of ventral striatum-related brain structural covariance and grey matter volume in forty-two first-episode patients with major depression disorder compared with thirty-seven healthy controls at the baseline and the one-year follow-up conditions. At the baseline, patients showed decreased structural covariance between the left ventral striatum and the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus (MFG), right supplementary motor area (SMA) and left precentral gyrus and increased grey matter volume at the left fusiform and left parahippocampus. At the one-year follow-up, patients showed decreased structural covariance between the left ventral striatum and the right SFG, right MFG, left precentral gyrus and left postcentral gyrus, and increased structural covariance between the right ventral striatum and the right amygdala, right hippocampus, right parahippocampus, right superior temporal pole, right insula and right olfactory bulb and decreased volume at the left SMA compared with controls. These findings suggest that specific ventral striatum connectivity changes contribute to the early brain development of the MDD.

The effect of chronic administration of oxycodone on the behavioral functions and histopathology in the cerebellum and striatum of adult male rats.

Oxycodone is widely used for pain management and acts via binding to mu- and kappa opioid receptors. It was shown that extended oxycodone usage can result from the demyelination and degeneration of neurons through the stress response, which triggers apoptotic signaling pathways. The striatum and cerebellum are recognized as significant contributors to addiction; however, there is no report on the effect of oxycodone on the cerebellum and striatum and motor coordination. We treated rats daily with oxycodone at 15 mg/kg doses for thirty days. Motor performance and electromyography activity were then evaluated. Stereological methods were performed to assess the number of neurons in the cerebellum and striatum as well as immunohistochemistry for microgliosis and astrogliosis. Furthermore, the Sholl analysis method was utilized to evaluate the cellular structure of both microglia and astrocytes. Results of the rotarod test for motor coordination show no significant (P < 0.05) difference between the oxycodone subjects and those in the control group. In addition, open-field assessments indicated that the application of oxycodone did not alter the amount of distance covered (as an indicator of locomotion) or time spent in the central area (as an indicator of anxiety) (P < 0.001). The electromyography (EMG) test result showed that oxycodone caused a delay in the reaction of the muscular nerves (P < 0.001). Data and results from our experiment revealed that administering oxycodone did not affect astrogliosis and the number of neurons in the cerebellum and striatum (P < 0.05). In contrast, it altered neuromuscular function. In addition, oxycodone administration activated microglia in the cerebellum and striatum. In conclusion, we encourage more research on the adverse effects of oxycodone on the brain.

Morning resting hypothalamus-dorsal striatum connectivity predicts individual differences in diurnal sleepiness accumulation.

While the significance of obtaining restful sleep at night and maintaining daytime alertness is well recognized for human performance and overall well-being, substantial variations exist in the development of sleepiness during diurnal waking periods. Despite the established roles of the hypothalamus and striatum in sleep-wake regulation, the specific contributions of this neural circuit in regulating individual sleep homeostasis remain elusive. This study utilized resting-state functional magnetic resonance imaging (fMRI) and mathematical modeling to investigate the role of hypothalamus-striatum connectivity in subjective sleepiness variation in a cohort of 71 healthy adults under strictly controlled in-laboratory conditions. Mathematical modeling results revealed remarkable individual differences in subjective sleepiness accumulation patterns measured by the Karolinska Sleepiness Scale (KSS). Brain imaging data demonstrated that morning hypothalamic connectivity to the dorsal striatum significantly predicts the individual accumulation of subjective sleepiness from morning to evening, while no such correlation was observed for the hypothalamus-ventral striatum connectivity. These findings underscore the distinct roles of hypothalamic connectivity to the dorsal and ventral striatum in individual sleep homeostasis, suggesting that hypothalamus-dorsal striatum circuit may be a promising target for interventions mitigating excessive sleepiness and promoting alertness.

Striatal GABA levels correlate with risk sensitivity in monetary loss.

Background: Decision-making under risk is a common challenge. It is known that risk-taking behavior varies between contexts of reward and punishment, yet the mechanisms underlying this asymmetry in risk sensitivity remain unclear. Methods: This study used a monetary task to investigate neurochemical mechanisms and brain dynamics underpinning risk sensitivity. Twenty-eight participants engaged in a task requiring selection of visual stimuli to maximize monetary gains and minimize monetary losses. We modeled participant trial-and-error processes using reinforcement learning. Results: Participants with higher subjective utility parameters showed risk preference in the gain domain (r = -0.59) and risk avoidance in the loss domain (r = -0.77). Magnetic resonance spectroscopy (MRS) revealed that risk avoidance in the loss domain was associated with γ-aminobutyric acid (GABA) levels in the ventral striatum (r = -0.42), but not in the insula (r = -0.15). Using functional magnetic resonance imaging (fMRI), we tested whether risk-sensitive brain dynamics contribute to participant risky choices. Energy landscape analyses demonstrated that higher switching rates between brain states, including the striatum and insula, were correlated with risk avoidance in the loss domain (r = -0.59), a relationship not observed in the gain domain (r = -0.02). Conclusions: These findings from MRS and fMRI suggest that distinct mechanisms are involved in gain/loss decision making, mediated by subcortical neurometabolite levels and brain dynamic transitions.

Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism.

Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.

Copper Overload Increased Rat Striatal Levels of Both Dopamine and Its Main Metabolite Homovanillic Acid in Extracellular Fluid.

Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for its effects on neurotransmission through modulation of GABAergic and glutamatergic receptors and interaction with the dopamine reuptake transporter. The aim of the present study was to investigate the effects of copper overexposure on the levels of dopamine, noradrenaline, and serotonin, or their main metabolites in rat's striatum extracellular fluid. Copper was injected intraperitoneally using our previously developed model, which ensured striatal overconcentration (2 mg CuCl2/kg for 30 days). Subsequently, extracellular fluid was collected by microdialysis on days 0, 15, and 30. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and noradrenaline (NA) levels were then determined by HPLC coupled with electrochemical detection. We observed a significant increase in the basal levels of DA and HVA after 15 days of treatment (310% and 351%), which was maintained after 30 days (358% and 402%), with no significant changes in the concentrations of 5-HIAA, DOPAC, and NA. Copper overload led to a marked increase in synaptic DA concentration, which could contribute to the psychoneurological alterations and the increased oxidative toxicity observed in Wilson's disease and other copper dysregulation states.

Anterior cingulate cortex lesions impair multiple facets of task engagement not mediated by dorsomedial striatum neuron firing.

The anterior cingulate cortex (ACC) has been implicated across multiple highly specialized cognitive functions-including task engagement, motivation, error detection, attention allocation, value processing, and action selection. Here, we ask if ACC lesions disrupt task performance and firing in dorsomedial striatum (DMS) during the performance of a reward-guided decision-making task that engages many of these cognitive functions. We found that ACC lesions impacted several facets of task performance-including decreasing the initiation and completion of trials, slowing reaction times, and resulting in suboptimal and inaccurate action selection. Reductions in movement times towards the end of behavioral sessions further suggested attenuations in motivation, which paralleled reductions in directional action selection signals in the DMS that were observed later in recording sessions. Surprisingly, however, beyond altered action signals late in sessions-neural correlates in the DMS were largely unaffected, even though behavior was disrupted at multiple levels. We conclude that ACC lesions result in overall deficits in task engagement that impact multiple facets of task performance during our reward-guided decision-making task, which-beyond impacting motivated action signals-arise from dysregulated attentional signals in the ACC and are mediated via downstream targets other than DMS.

Utilising activity patterns of a complex biophysical network model to optimise intra-striatal deep brain stimulation.

A large-scale biophysical network model for the isolated striatal body is developed to optimise potential intrastriatal deep brain stimulation applied to, e.g. obsessive-compulsive disorder. The model is based on modified Hodgkin-Huxley equations with small-world connectivity, while the spatial information about the positions of the neurons is taken from a detailed human atlas. The model produces neuronal spatiotemporal activity patterns segregating healthy from pathological conditions. Three biomarkers were used for the optimisation of stimulation protocols regarding stimulation frequency, amplitude and localisation: the mean activity of the entire network, the frequency spectrum of the entire network (rhythmicity) and a combination of the above two. By minimising the deviation of the aforementioned biomarkers from the normal state, we compute the optimal deep brain stimulation parameters, regarding position, amplitude and frequency. Our results suggest that in the DBS optimisation process, there is a clear trade-off between frequency synchronisation and overall network activity, which has also been observed during in vivo studies.

Astrocyte Gi-GPCR signaling corrects compulsive-like grooming and anxiety-related behaviors in Sapap3 knockout mice.

Astrocytes are morphologically complex cells that serve essential roles. They are widely implicated in central nervous system (CNS) disorders, with changes in astrocyte morphology and gene expression accompanying disease. In the Sapap3 knockout (KO) mouse model of compulsive and anxiety-related behaviors related to obsessive-compulsive disorder (OCD), striatal astrocytes display reduced morphology and altered actin cytoskeleton and Gi-G-protein-coupled receptor (Gi-GPCR) signaling proteins. Here, we show that normalizing striatal astrocyte morphology, actin cytoskeleton, and essential homeostatic support functions by targeting the astrocyte Gi-GPCR pathway using chemogenetics corrected phenotypes in Sapap3 KO mice, including anxiety-related and compulsive behaviors. Our data portend an astrocytic pharmacological strategy for rescuing phenotypes in brain disorders that include compromised astrocyte morphology and tissue support.

Nothing to lose? Neural correlates of decision, anticipation, and feedback in the balloon analog risk task.

Understanding the subprocesses of risky decision making is a prerequisite for understanding (dys-)functional decisions. For the present fMRI study, we designed a novel variant of the balloon-analog-risk task (BART) that measures three phases: decision making, reward anticipation, and feedback processing. Twenty-nine healthy young adults completed the BART. We analyzed neural activity and functional connectivity. Parametric modulation allowed assessing changes in brain functioning depending on the riskiness of the decision. Our results confirm involvement of nucleus accumbens, insula, anterior cingulate cortex, and dorsolateral prefrontal cortex in all subprocesses of risky decision-making. In addition, subprocesses were differentiated by the strength of activation in these regions, as well as by changes in activity and nucleus accumbens-connectivity by the riskiness of the decision. The presented fMRI-BART variant allows distinguishing activity and connectivity during the subprocesses of risky decision making and shows how activation and connectivity patterns relate to the riskiness of the decision. Hence, it is a useful tool for unraveling impairments in subprocesses of risky decision making in people with high risk behavior.

Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans.

Ultra-processed foods high in fat and sugar may be addictive, in part, due to their purported ability to induce an exaggerated postingestive brain dopamine response akin to drugs of abuse. Using standard [11C]raclopride positron emission tomography (PET) displacement methods used to measure brain dopamine responses to addictive drugs, we measured postingestive striatal dopamine responses to an ultra-processed milkshake high in fat and sugar in 50 young, healthy adults over a wide body mass index range (BMI 20-45 kg/m2). Surprisingly, milkshake consumption did not result in significant postingestive dopamine response in the striatum (p=0.62) nor any striatal subregion (p>0.33) and the highly variable interindividual responses were not significantly related to adiposity (BMI: r=0.076, p=0.51; %body fat: r=0.16, p=0.28). Thus, postingestive striatal dopamine responses to an ultra-processed milkshake were likely substantially smaller than many addictive drugs and below the limits of detection using standard PET methods.

Activation and polarization of striatal microglia and astrocytes are involved in bradykinesia and allodynia in early-stage parkinsonian mice.

In addition to the cardinal motor symptoms, pain is a major non-motor symptom of Parkinson's disease (PD). Neuroinflammation in the substantia nigra pars compacta and dorsal striatum is involved in neurodegeneration in PD. But the polarization of microglia and astrocytes in the dorsal striatum and their contribution to motor deficits and hyperalgesia in PD have not been characterized. In the present study, we observed that hemiparkinsonian mice established by unilateral 6-OHDA injection in the medial forebrain bundle exhibited motor deficits and mechanical allodynia. In these mice, both microglia and astrocytes in the dorsal striatum were activated and polarized to M1/M2 microglia and A1/A2 astrocytes as genes specific to these cells were upregulated. These effects peaked 7 days after 6-OHDA injection. Meanwhile, striatal astrocytes in parkinsonian mice also displayed hyperpolarized membrane potentials, enhanced voltage-gated potassium currents, and dysfunction in inwardly rectifying potassium channels and glutamate transporters. Systemic administration of minocycline, a microglia inhibitor, attenuated the expression of genes specific to M1 microglia and A1 astrocytes in the dorsal striatum (but not those specific to M2 microglia and A2 astrocytes), attenuated the damage in the nigrostriatal dopaminergic system, and alleviated the motor deficits and mechanical allodynia in parkinsonian mice. By contrast, local administration of minocycline into the dorsal striatum of parkinsonian mice mitigated only hyperalgesia. This study suggests that M1 microglia and A1 astrocytes in the dorsal striatum may play important roles in the development of pathophysiology underlying hyperalgesia in the early stages of PD.

Motor cortex is responsible for motoric dynamics in striatum and the execution of both skilled and unskilled actions.

Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion's direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions. Although some aspects of performance began to recover after 8-10 days, striatal projection and interneuronal dynamics did not-eventually entering a non-motor encoding state that aligned with persisting kinematic control deficits. Lesioned mice also exhibited a profound inability to switch motor plans while locomoting, reminiscent of clinical freezing of gait (FOG). Our results demonstrate the necessity of motor cortex in generating trained and untrained actions as well as striatal motoric dynamics.

Brain mechanisms of temporal processing in impulsivity: Relevance to attention-deficit hyperactivity disorder.

In this article, we critique the hypothesis that different varieties of impulsivity, including impulsiveness present in attention-deficit hyperactivity disorder, encompass an accelerated perception of time. This conceptualisation provides insights into how individuals with attention-deficit hyperactivity disorder have the capacity to maximise cognitive capabilities by more closely aligning themselves with appropriate environmental contexts (e.g. fast paced tasks that prevent boredom). We discuss the evidence for altered time perception in attention-deficit hyperactivity disorder alongside putative underlying neurobiological substrates, including a distributed brain network mediating time perception over multiple timescales. In particular, we explore the importance of temporal representations across the brain for time perception and symptom manifestation in attention-deficit hyperactivity disorder, including a prominent role of the hippocampus and other temporal lobe regions. We also reflect on how abnormalities in the perception of time may be relevant for understanding the aetiology of attention-deficit hyperactivity disorder and mechanism of action of existing medications.

Methylphenidate Exposing During Neurodevelopment Alters Amino Acid Profile, Astrocyte Marker and Glutamatergic Excitotoxicity in the Rat Striatum.

There is a public health concern about the use of methylphenidate (MPH) since the higher prescription for young individuals and non-clinical purposes is addressed to the limited understanding of its neurochemical and psychiatric consequences. This study aimed to evaluate the impact of early and chronic MPH treatment on the striatum focusing on amino acid profile, glutamatergic excitotoxicity, redox status, neuroinflammation and glial cell responses. Male Wistar rats were treated with MPH (2.0 mg/kg) or saline solution from the 15th to the 44th postnatal day. Biochemical and histological analyses were conducted after the last administration. MPH altered the amino acid profile in the striatum, increasing glutamate and ornithine levels, while decreasing the levels of serine, phenylalanine, and branched-chain amino acids (leucine, valine, and isoleucine). Glutamate uptake and Na+,K+-ATPase activity were decreased in the striatum of MPH-treated rats as well as increased ATP levels, as indicator of glutamatergic excitotoxicity. Moreover, MPH caused lipid peroxidation and nitrative stress, increased TNF alpha expression, and induced high levels of astrocytes, and led to a decrease in BDNF levels. In summary, our results suggest that chronic early-age treatment with MPH induces parallel activation of damage-associated pathways in the striatum and increases its vulnerability during the juvenile period. In addition, data presented here contribute to shedding light on the mechanisms underlying MPH-induced striatal damage and its potential implications for neurodevelopmental disorders.

Heterogeneous brain region-specific responses to astrocytic mitochondrial DNA damage in mice.

Astrocytes display context-specific diversity in their functions and respond to noxious stimuli between brain regions. Astrocytic mitochondria have emerged as key players in governing astrocytic functional heterogeneity, given their ability to dynamically adapt their morphology to regional demands on ATP generation and Ca2+ buffering functions. Although there is reciprocal regulation between mitochondrial dynamics and mitochondrial Ca2+ signaling in astrocytes, the extent of this regulation in astrocytes from different brain regions remains unexplored. Brain-wide, experimentally induced mitochondrial DNA (mtDNA) loss in astrocytes showed that mtDNA integrity is critical for astrocyte function, however, possible diverse responses to this noxious stimulus between brain areas were not reported in these experiments. To selectively damage mtDNA in astrocytes in a brain-region-specific manner, we developed a novel adeno-associated virus (AAV)-based tool, Mito-PstI expressing the restriction enzyme PstI, specifically in astrocytic mitochondria. Here, we applied Mito-PstI to two brain regions, the dorsolateral striatum and dentate gyrus, and we show that Mito-PstI induces astrocytic mtDNA loss in vivo, but with remarkable brain-region-dependent differences on mitochondrial dynamics, Ca2+ fluxes, and astrocytic and microglial reactivity. Thus, AAV-Mito-PstI is a novel tool to explore the relationship between astrocytic mitochondrial network dynamics and astrocytic mitochondrial Ca2+ signaling in a brain-region-selective manner.