Browsing by Subject "PLASTICITY"

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  • Acosta, H.; Tuulari, J. J.; Kantojärvi, K.; Lewis, J. D.; Hashempour, N.; Scheinin, N. M.; Lehtola, S. J.; Fonov, V. S.; Collins, D. L.; Evans, A.; Parkkola, R.; Lahdesmaki, T.; Saunavaara, J.; Merisaari, H.; Karlsson, L.; Paunio, T.; Karlsson, H. (2021)
    Genetic variants in the oxytocin receptor (OTR) have been linked to distinct social phenotypes, psychiatric disorders and brain volume alterations in adults. However, to date, it is unknown how OTR genotype shapes prenatal brain development and whether it interacts with maternal prenatal environmental risk factors on infant brain volumes. In 105 Finnish mother-infant dyads (44 female, 11-54 days old), the association of offspring OTR genotype rs53576 and its interaction with prenatal maternal anxiety (revised Symptom Checklist 90, gestational weeks 14, 24, 34) on infant bilateral amygdalar, hippocampal and caudate volumes were probed. A sex-specific main effect of rs53576 on infant left hippocampal volumes was observed. In boys compared to girls, left hippocampal volumes were significantly larger in GG-homozygotes compared to A-allele carriers. Furthermore, genotype rs53576 and prenatal maternal anxiety significantly interacted on right hippocampal volumes irrespective of sex. Higher maternal anxiety was associated both with larger hippocampal volumes in A allele carriers than GG-homozygotes, and, though statistically weak, also with smaller right caudate volumes in GG-homozygotes than A-allele carriers. Our study results suggest that OTR genotype enhances hippocampal neurogenesis in male GG-homozygotes. Further, prenatal maternal anxiety might induce brain alterations that render GG-homozygotes compared to A-allele carriers more vulnerable to depression.
  • Alitalo, Okko; Saarreharju, Roosa; Henter, Ioline D.; Jr, Carlos A. Zarate; Kohtala, Samuel; Rantamäki, Tomi (2021)
    Depression is frequently associated with sleep problems, and clinical improvement often coincides with the normalization of sleep architecture and realignment of circadian rhythm. The effectiveness of treatments targeting sleep in depressed patients, such as sleep deprivation, further demonstrates the confluence of sleep and mood. Moreover, recent studies showing that the rapid-acting antidepressant ketamine influences processes related to sleep-wake neurobiology have led to novel hypotheses explaining rapid and sustained antidepressant effects. Despite the available evidence, studies addressing ketamine's antidepressant effects have focused on pharmacology and often overlooked the role of physiology. To explore this discrepancy in research on rapid acting antidepressants, we examined articles published between 2009-2019. A keyword search algorithm indicated that vast majority of the articles completely ignored sleep. Out of the 100 most frequently cited pre clinical and clinical research papers, 89 % and 71 %, respectively, did not mention sleep at all. Furthermore, only a handful of these articles disclosed key experimental variables, such as the times of treatment administration or behavioral testing, let alone considered the potential association between these variables and experimental observations. Notably, in preclinical studies, treatments were preferentially administered during the inactive period, which is the polar opposite of clinical practice and research. We discuss the potential impact of this practice on the results in the field. Our hope is that this perspective will serve as a wake-up call to (re)-examine rapid-acting antidepressant effects with more appreciation for the role of sleep and chronobiology.
  • Burunat, Iballa; Brattico, Elvira; Puoliväli, Tuomas; Ristaniemi, Tapani; Sams, Mikko; Toiviainen, Petri (2015)
    Musical training leads to sensory and motor neuroplastic changes in the human brain. Motivated by findings on enlarged corpus callosum in musicians and asymmetric somatomotor representation in string players, we investigated the relationship between musical training, callosal anatomy, and interhemispheric functional symmetry during music listening. Functional symmetry was increased in musicians compared to nonmusicians, and in keyboardists compared to string players. This increased functional symmetry was prominent in visual and motor brain networks. Callosal size did not significantly differ between groups except for the posterior callosum in musicians compared to nonmusicians. We conclude that the distinctive postural and kinematic symmetry in instrument playing cross-modally shapes information processing in sensory-motor cortical areas during music listening. This cross-modal plasticity suggests that motor training affects music perception.
  • Radchuk, Viktoriia; Reed, Thomas; Teplitsky, Celine; van de Pol, Martijn; Charmantier, Anne; Hassall, Christopher; Adamik, Peter; Adriaensen, Frank; Ahola, Markus P.; Arcese, Peter; Miguel Aviles, Jesus; Balbontin, Javier; Berg, Karl S.; Borras, Antoni; Burthe, Sarah; Clobert, Jean; Dehnhard, Nina; de Lope, Florentino; Dhondt, Andre A.; Dingemanse, Niels J.; Doi, Hideyuki; Eeva, Tapio; Fickel, Joerns; Filella, Iolanda; Fossoy, Frode; Goodenough, Anne E.; Hall, Stephen J. G.; Hansson, Bengt; Harris, Michael; Hasselquist, Dennis; Hickler, Thomas; Joshi, Jasmin; Kharouba, Heather; Gabriel Martinez, Juan; Mihoub, Jean-Baptiste; Mills, James A.; Molina-Morales, Mercedes; Moksnes, Arne; Ozgul, Arpat; Parejo, Deseada; Pilard, Philippe; Poisbleau, Maud; Rousset, Francois; Roedel, Mark-Oliver; Scott, David; Carlos Senar, Juan; Stefanescu, Constanti; Stokke, Bard G.; Kusano, Tamotsu; Tarka, Maja; Tarwater, Corey E.; Thonicke, Kirsten; Thorley, Jack; Wilting, Andreas; Tryjanowski, Piotr; Merilä, Juha; Sheldon, Ben C.; Moller, Anders Pape; Matthysen, Erik; Janzen, Fredric; Dobson, F. Stephen; Visser, Marcel E.; Beissinger, Steven R.; Courtiol, Alexandre; Kramer-Schadt, Stephanie (2019)
    Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
  • Sakha, Prasanna; Vesikansa, Aino; Orav, Ester; Heikkinen, Joonas; Kukko-Lukjanov, Tiina-Kaisa; Shintyapina, Alexandra; Franssila, Sami; Jokinen, Ville; Huttunen, Henri J.; Lauri, Sari E. (2016)
    Kainate type of glutamate receptors (KARs) are highly expressed during early brain development and may influence refinement of the circuitry, via modulating synaptic transmission and plasticity. KARs are also localized to axons, however, their exact roles in regulating presynaptic processes remain controversial. Here, we have used a microfluidic chamber system allowing specific manipulation of KARs in presynaptic neurons to study their functions in synaptic development and function in vitro. Silencing expression of endogenous KARs resulted in lower density of synaptophysin immunopositive puncta in microfluidically isolated axons. Various recombinant KAR subunits and pharmacological compounds were used to dissect the mechanisms behind this effect. The calcium permeable (Q) variants of the low-affinity (GluK1-3) subunits robustly increased synaptophysin puncta in axons in a manner that was dependent on receptor activity and PKA and PKC dependent signaling. Further, an associated increase in the mean active zone length was observed in electron micrographs. Selective presynaptic expression of these subunits resulted in higher success rate of evoked EPSCs consistent with higher probability of glutamate release. In contrast, the calcium-impermeable (R) variant of GluK1 or the high-affinity subunits (GluK4,5) had no effect on synaptic density or transmission efficacy. These data suggest that calcium permeable axonal KARs promote efferent connectivity by increasing the density of functional presynaptic release sites.
  • Pentikäinen, Emmi; Pitkäniemi, Anni; Siponkoski, Sini-Tuuli; Jansson, Maarit; Louhivuori, Jukka; Johnson, Julene K.; Paajanen, Teemu; Särkämö, Teppo (2021)
    Background and objectives Choir singing has been associated with better mood and quality of life (QOL) in healthy older adults, but little is known about its potential cognitive benefits in aging. In this study, our aim was to compare the subjective (self-reported) and objective (test-based) cognitive functioning of senior choir singers and matched control subjects, coupled with assessment of mood, QOL, and social functioning. Research design and methods We performed a cross-sectional questionnaire study in 162 healthy older (age >= 60 years) adults (106 choir singers, 56 controls), including measures of cognition, mood, social engagement, QOL, and role of music in daily life. The choir singers were divided to low (1-10 years, N = 58) and high (>10 years, N = 48) activity groups based on years of choir singing experience throughout their life span. A subcohort of 74 participants (39 choir singers, 35 controls) were assessed also with a neuropsychological testing battery. Results In the neuropsychological testing, choir singers performed better than controls on the verbal flexibility domain of executive function, but not on other cognitive domains. In questionnaires, high activity choir singers showed better social integration than controls and low activity choir singers. In contrast, low activity choir singers had better general health than controls and high activity choir singers. Discussion and implications In healthy older adults, regular choir singing is associated with better verbal flexibility. Long-standing choir activity is linked to better social engagement and more recently commenced choir activity to better general health.
  • Steinzeig, Anna; Molotkov, Dmitry; Castren, Eero (2017)
    Growing interest in long-term visualization of cortical structure and function requires methods that allow observation of an intact cortex in longitudinal imaging studies. Here we describe a detailed protocol for the "transparent skull" (TS) preparation based on skull clearing with cyanoacrylate, which is applicable for long-term imaging through the intact skull in mice. We characterized the properties of the TS in imaging of intrinsic optical signals and compared them with the more conventional cranial window preparation. Our results show that TS is less invasive, maintains stabile transparency for at least two months, and compares favorably to data obtained from the conventional cranial window. We applied this method to experiments showing that a four-week treatment with the antidepressant fluoxetine combined with one week of monocular deprivation induced a shift in ocular dominance in the mouse visual cortex, confirming that fluoxetine treatment restores critical-period-like plasticity. Our results demonstrate that the TS preparation could become a useful method for long-term visualization of the living mouse brain.
  • Sihvonen, Aleksi J.; Särkämö, Teppo (2021)
    Patients with post-stroke impairments present often significant variation in response to therapeutic interventions. Recent studies have shown that daily music listening can aid post-stroke recovery of language and memory, but reliable predictors of treatment response are unknown. Utilizing data from the music intervention arms of a single-blind randomized controlled trial (RCT) on stroke patients (N = 31), we built regression models to predict the treatment response of a two-month music listening intervention on language skills and verbal memory with baseline demographic, clinical and musical data as well as fMRI data from a music listening task. Clinically, greater improvement in verbal memory and language skills after the music listening intervention were predicted by the severity of the initial deficit and educational level. Neurally, greater baseline fMRI activation during vocal music listening in the left parietal cortical and medial frontal areas predicted greater treatment-induced improvement in language skills and greater baseline engagement of the auditory network during instrumental music listening predicted improvement in both verbal memory and language skills. Our results suggest that clinical, demographic, and neuroimaging data predicts music listening treatment response. This data could be used clinically to target music-based treatments.
  • Tervo, Aino E.; Nieminen, Jaakko O.; Lioumis, Pantelis; Metsomaa, Johanna; Souza, Victor H.; Sinisalo, Heikki; Stenroos, Matti; Sarvas, Jukka; Ilmoniemi, Risto J. (2022)
    Background: Transcranial magnetic stimulation (TMS) is widely used in brain research and treatment of various brain dysfunctions. However, the optimal way to target stimulation and administer TMS therapies, for example, where and in which electric field direction the stimuli should be given, is yet to be determined. Objective: To develop an automated closed-loop system for adjusting TMS parameters (in this work, the stimulus orientation) online based on TMS-evoked brain activity measured with electroencephalography (EEG). Methods: We developed an automated closed-loop TMS-EEG set-up. In this set-up, the stimulus parameters are electronically adjusted with multi-locus TMS. As a proof of concept, we developed an algorithm that automatically optimizes the stimulation orientation based on single-trial EEG responses. We applied the algorithm to determine the electric field orientation that maximizes the amplitude of the TMS-EEG responses. The validation of the algorithm was performed with six healthy volunteers, repeating the search twenty times for each subject. Results: The validation demonstrated that the closed-loop control worked as desired despite the large variation in the single-trial EEG responses. We were often able to get close to the orientation that maximizes the EEG amplitude with only a few tens of pulses. Conclusion: Optimizing stimulation with EEG feedback in a closed-loop manner is feasible and enables effective coupling to brain activity. (C) 2022 The Author(s). Published by Elsevier Inc.
  • Hujanen, Roosa; Almahmoudi, Rabeia; Salo, Tuula; Salem, Abdelhakim (2021)
    Tissue vasculature provides the main conduit for metastasis in solid tumours including head and neck squamous cell carcinoma (HNSCC). Vascular mimicry (VM) is an endothelial cell (EC)-independent neovascularization pattern, whereby tumour cells generate a perfusable vessel-like meshwork. Yet, despite its promising clinical utility, there are limited approaches to better identify VM in HNSCC and what factors may influence such a phenomenon in vitro. Therefore, we employed different staining procedures to assess their utility in identifying VM in tumour sections, wherein mosaic vessels may also be adopted to further assess the VM-competent cell phenotype. Using 13 primary and metastatic HNSCC cell lines in addition to murine- and human-derived matrices, we elucidated the impact of the extracellular matrix, tumour cell type, and density on the formation and morphology of cell-derived tubulogenesis in HNSCC. We then delineated the optimal cell numbers needed to obtain a VM meshwork in vitro, which revealed cell-specific variations and yet consistent expression of the EC marker CD31. Finally, we proposed the zebrafish larvae as a simple and cost-effective model to evaluate VM development in vivo. Taken together, our findings offer a valuable resource for designing future studies that may facilitate the therapeutic exploitation of VM in HNSCC and other tumours.
  • Vanhanen, Jukka; Parkkonen, Lauri; Mäkelä, Jyrki P.; Tolmacheva, Alexandra; Shulga, Anastasia; Rodionov, Andrey; Kirveskari, Erika (2022)
    Study design A prospective interventional case series. Objectives To explore changes in the modulation of cortical sensorimotor oscillations after long-term paired associative stimulation (PAS) in participants with spinal cord injury (SCI). Setting BioMag Laboratory, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Methods Five patients with chronic incomplete SCI received unilateral spinal PAS to upper limb for 16-22 days. Changes in the modulation of sensorimotor oscillations in response to tactile stimulus and active and imaginary hand movements were assessed with magnetoencephalography recorded before and after the intervention. Results PAS restored the modulation of sensorimotor oscillations in response to active hand movement in four patients, whereas the modulation following tactile stimulation remained unaltered. The observed change was larger in the hemisphere that received PAS and preceded the clinical effect of the intervention. Conclusions Long-term spinal PAS treatment, which enhances the motor functions of SCI patients, also restores the modulation of cortical sensorimotor oscillations.
  • Rodionov, Andrei; Savolainen, Sarianna; Kirveskari, Erika; Mäkelä, Jyrki P.; Shulga, Anastasia (2020)
    Recovery of lower-limb function after spinal cord injury (SCI) is dependent on the extent of remaining neural transmission in the corticospinal pathway. The aim of this proof-of-concept pilot study was to explore the effects of long-term paired associative stimulation (PAS) on leg muscle strength and walking in people with SCI. Five individuals with traumatic incomplete chronic tetraplegia (>34 months post-injury, motor incomplete, 3 females, mean age 60 years) with no contraindications to transcranial magnetic stimulation (TMS) received PAS to one or both legs for 2 months (28 sessions in total, 5 times a week for the first 2 weeks and 3 times a week thereafter). The participants were evaluated with the Manual Muscle Test (MMT), AIS motor and sensory examination, Modified Asworth Scale (MAS), and the Spinal Cord Independence Measure (SCIM) prior to the intervention, after 1 and 2 months of PAS, and after a 1-month follow-up. The study was registered at (NCT03459885). During the intervention, MMT scores and AIS motor scores increased significantly (p = 0.014 and p = 0.033, respectively). Improvements were stable in follow-up. AIS sensory scores, MAS, and SCIM were not modified significantly. MMT score prior to intervention was a good predictor of changes in walking speed (Radj2 = 0.962). The results of this proof-of-concept pilot study justify a larger trial on the effect of long-term PAS on leg muscle strength and walking in people with chronic incomplete SCI.
  • Ämmälä, Antti Jussi; Urrila, Anna Sofia; Lahtinen, Aleksandra; Santangeli, Olena; Hakkarainen, Antti; Kantojärvi, Katri; Castaneda, Anu E.; Lundbom, Nina; Marttunen, Mauri; Paunio, Tiina (2019)
    Objectives: This study aimed to test the hypothesis that sleep and depression have independent effects on brain development and plasticity in adolescents, and that these changes are reflected in changes in the epigenome. Methods: Participants were 17 medication-free adolescent boys (age 16.05 +/- 0.80 years, mean +/- standard deviation (SD); eight cases with depression and sleep symptoms, nine healthy controls). Sleep was assessed by polysomnography recordings and the Pediatric Daytime Sleepiness Scale (PDSS) and Athens Insomnia Scale (AIS). Participants underwent a clinical evaluation. DNA methylation of blood leukocytes was measured by Illumina 450K array, and Ingenuity Pathway analysis was applied to identify the most significant pathways with differentially methylated positions (DMPs). Secondary analysis of the identified loci included linear correlations between methylation and the subjectively rated scales of sleep, depression and sleep microarchitecture. Results: Due to small sample size, we found no genome-wide significant differences in methylation between cases and controls. However, pathway analysis identified the synaptic long-term depression (LTD) canonical pathway (p = 0.00045) when the best 500 DMPs from the original case-control design were included. A flattened dissipation of slow wave sleep, tiredness and depression severity values correlated with five of 10 sites from the LTD pathway (IGF1R, PLAG16, PLA2R1, PPP2C5 and ERK12) in the secondary analysis when the case-control status was controlled for. Conclusion: Among adolescents, depressive disorder with sleep symptoms is associated with a distinctive epigenetic pattern of DNA methylation in blood leukocytes. The enrichment of DMPs on genes related to synaptic LTD emphasizes the role of sleep in synaptic plasticity and the widespread physiological consequences of disturbed sleep. (C) 2019 Elsevier B.V. All rights reserved.
  • Huttunen, Henri J.; Palva, J. Matias; Lindberg, Laura; Palva, Satu; Saarela, Ville; Karvonen, Elina; Latvala, Marja-Leena; Liinamaa, Johanna; Booms, Sigrid; Castren, Eero; Uusitalo, Hannu (2018)
    Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: -0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from baseline to 10 weeks in both fluoxetine (-0.167 logMAR; 95% CI: -0.226 to -0.108; p <0.001) and placebo (-0.194 logMAR; 95% CI: -0.254 to -0.133; p <0.001) groups. While this study failed to provide evidence that fluoxetine enhances neuroplasticity, our data support other recent clinical studies suggesting that improvement of vision can be accomplished in adults with amblyopia.
  • Nava, Michele M.; Miroshnikova, Yekaterina A.; Biggs, Leah C.; Whitefield, Daniel B.; Metge, Franziska; Boucas, Jorge; Vihinen, Helena; Jokitalo, Eija; Li, Xinping; García Arcos, Juan Manuel; Hoffmann, Bernd; Merkel, Rudolf; Niessen, Carien M.; Dahl, Kris Noel; Wickström, Sara A. (2020)
    Summary Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin. The resulting changes in chromatin rheology and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage. Persistent, high-amplitude stretch induces supracellular alignment of tissue to redistribute mechanical energy before it reaches the nucleus. This tissue-scale mechanoadaptation functions through a separate pathway mediated by cell-cell contacts and allows cells/tissues to switch off nuclear mechanotransduction to restore initial chromatin state. Our work identifies an unconventional role of chromatin in altering its own mechanical state to maintain genome integrity in response to deformation.
  • Ning, Lin; Paetau, Sonja; Nyman-Huttunen, Henrietta; Tian, Li; Gahmberg, Carl G. (2015)
    ICAM-5 is a negative regulator of dendritic spine maturation and facilitates the formation of filopodia. Its absence results in improved memory functions, but the mechanisms have remained poorly understood. Activation of NMDA receptors induces ICAM-5 ectodomain cleavage through a matrix metalloproteinase (MMP)-dependent pathway, which promotes spine maturation and synapse formation. Here, we report a novel, ICAM-5-dependent mechanism underlying spine maturation by regulating the dynamics and synaptic distribution of a-actinin. We found that GluN1 and ICAM-5 partially compete for the binding to alpha-actinin; deletion of the cytoplasmic tail of ICAM-5 or ablation of the gene resulted in increased association of GluN1 with alpha-actinin, whereas internalization of ICAM-5 peptide perturbed the GluN1/alpha-actinin interaction. NMDA treatment decreased alpha-actinin binding to ICAM-5, and increased the binding to GluN1. Proper synaptic distribution of alpha-actinin requires the ICAM-5 cytoplasmic domain, without which alpha-actinin tended to accumulate in filopodia, leading to F-actin reorganization. The results indicate that ICAM-5 retards spine maturation by preventing reorganization of the actin cytoskeleton, but NMDA receptor activation is sufficient to relieve the brake and promote the maturation of spines.
  • Komulainen, Emilia; Varidaki, Artemis; Kulesskaya, Natalia; Mohammad, Hasan; Sourander, Christel; Rauvala, Heikki; Coffey, Eleanor T. (2020)
    The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory proteins. JNK1 also phosphorylates dendritic spine proteins, and Jnk1-/- mice display a long-term depression deficit. Whether JNK1 or other JNKs regulate spine morphology is thus of interest. Here, we characterize dendritic spine morphology in hippocampus of mice lacking Jnk1-/- using Lucifer yellow labelling. We find that mushroom spines decrease and thin spines increase in apical dendrites of CA3 pyramidal neurons with no spine changes in basal dendrites or in CA1. Consistent with this spine deficit, Jnk1-/- mice display impaired acquisition learning in the Morris water maze. In hippocampal cultures, we show that cytosolic but not nuclear JNK, regulates spine morphology and expression of phosphomimicry variants of JNK substrates doublecortin (DCX) or myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1), rescue mushroom, thin, and stubby spines differentially. These data suggest that physiologically active JNK controls the equilibrium between mushroom, thin, and stubby spines via phosphorylation of distinct substrates.
  • Laukkanen, Virpi; Kärkkäinen, Olli; Kautiainen, Hannu; Tiihonen, Jari; Storvik, Markus (2019)
    The function of group I metabotropic glutamate receptors mGluR1 and mGluR5 is involved in the hyperglutamatergic state caused by chronic alcohol. Preclinical studies suggest that group I mGluR modulation could serve as a novel treatment of alcoholism. Considering the wide role of glutamatergic neurochemistry in addiction, group I mGluR binding was studied in brain areas involved in decision-making, learning and memory. Post-mortem whole hemisphere autoradiography was used to study the binding density of [H-3] quisqualic acid, a potent group I mGluR agonist, in 9 Cloninger type 1 alcoholics, 8 Cloninger type 2 alcoholics and 10 controls. Binding was studied in the dorsal striatum, hippocampus and cortex. Alcoholics displayed a trend towards increased [ H-3] quisqualic acid binding in all brain areas. The most robust findings were in the putamen (p = 0.006) and anterior insula (p = 0.005), where both alcoholic subtypes displayed increased binding compared to the controls. These findings suggest altered group I mGluR function in alcoholic subjects in the dorsal striatum, which is involved in habitual learning, and in the anterior insula, which has a pivotal role in the perception of bodily sensations. Increased [H-3] quisqualic acid binding might suggest a beneficial impact of mGluR1/5 modulators in the treatment of alcoholism.