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Cacna1c memory

Donna Cosgrove, Omar Mothersill, Kimberley Kendall, Bettina Konte, Denise Harold, Ina Giegling, Annette Hartmann, Alex Richards, Kiran Mantripragada, Michael J Owen, Michael C O'Donovan, Michael Gill, Dan Rujescu, James Walters, Aiden Corvin, Derek W Morris, Gary Donohoe
With >100 common variants associated with schizophrenia risk, establishing their biological significance is a priority. We sought to establish cognitive effects of risk variants at loci implicated in synaptic transmission by (1) identifying GWAS schizophrenia variants whose associated gene function is related to synaptic transmission, and (2) testing for association between these and measures of neurocognitive function. We selected variants, reported in the largest GWAS to date, associated with genes involved in synaptic transmission...
December 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Z D Kabir, A Che, D K Fischer, R C Rice, B K Rizzo, M Byrne, M J Glass, N V De Marco Garcia, A M Rajadhyaksha
CACNA1C, encoding the Cav 1.2 subunit of L-type Ca2+ channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav 1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav 1...
August 2017: Molecular Psychiatry
Marco Calabrò, Laura Mandelli, Concetta Crisafulli, Antonella Sidoti, Tae-Youn Jun, Soo-Jung Lee, Changsu Han, Ashwin A Patkar, Prakash S Masand, Chi-Un Pae, Alessandro Serretti
BACKGROUND: Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning. METHODS: One hundred and thirty-two subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1...
2016: Neuropsychobiology
Charlotte C Bavley, Delaney K Fischer, Bryant K Rizzo, Anjali M Rajadhyaksha
Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene CACNA1C , which codes for the Cav 1.2 subunit of the L-type calcium channel (LTCC), as a common risk variant for multiple neuropsychiatric conditions. Cav 1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways...
December 2017: Neurobiology of Stress
Stephanie J Temme, Ryan Z Bell, Grace L Fisher, Geoffrey G Murphy
L-type voltage-gated calcium channels (LVGCCs) have been implicated in various forms of learning, memory, and synaptic plasticity. Within the hippocampus, the LVGCC subtype, CaV 1.2 is prominently expressed throughout the dentate gyrus. Despite the apparent high levels of CaV 1.2 expression in the dentate gyrus, the role of CaV 1.2 in hippocampal- and dentate gyrus-associated forms of learning remain unknown. To address this question, we examined alternate forms of hippocampal-dependent associative and spatial memory in mice lacking the mouse ortholog of CACNA1C ( Cacna1c ), which encodes CaV 1...
November 2016: ENeuro
Akito Nakao, Takafumi Miki, Hirotaka Shoji, Miyuki Nishi, Hiroshi Takeshima, Tsuyoshi Miyakawa, Yasuo Mori
Calcium (Ca(2+)) influx through voltage-gated Ca(2+) channels (VGCCs) induces numerous intracellular events such as neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation. It has been shown that genes related to Ca(2+) signaling, such as the CACNA1C, CACNB2, and CACNA1I genes that encode VGCC subunits, are associated with schizophrenia and other psychiatric disorders. Recently, VGCC beta-anchoring and -regulatory protein (BARP) was identified as a novel regulator of VGCC activity via the interaction of VGCC β subunits...
2015: Frontiers in Behavioral Neuroscience
Panos Zanos, Shambhu Bhat, Chantelle E Terrillion, Robert J Smith, Leonardo H Tonelli, Todd D Gould
Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively...
October 2015: European Journal of Neuroscience
Gen Shinozaki, James B Potash
The last several years have been breakthrough ones in bipolar disorder (BPD) genetics, as the field has identified robust risk variants for the first time. Leading the way have been genome-wide association studies (GWAS) that have assessed common genetic markers across very large groups of patients and controls. These have resulted in findings in genes including ANK3, CACNA1C, SYNE1, ODZ4, and TRANK1. Additional studies have begun to examine the biology of these genes and how risk variants influence aspects of brain and behavior that underlie BPD...
November 2014: Current Psychiatry Reports
Stefan M Berger, Dusan Bartsch
The use of specific activators and inhibitors that penetrate the central nervous system has suggested an essential functional role of L-type calcium channels (LTCC) in several important physiological processes of the brain, including the modulation of the mesoaccumbal dopamine signalling pathway, synaptic transmission of auditory stimuli and synaptic plasticity of neutral and aversive learning and memory processes. However, the lack of selectivity of available pharmacological agents towards the most prominent LTCC isoforms in the brain, namely Cav1...
August 2014: Cell and Tissue Research
B H Schott, A Assmann, P Schmierer, J Soch, S Erk, M Garbusow, S Mohnke, L Pöhland, N Romanczuk-Seiferth, A Barman, T Wüstenberg, L Haddad, O Grimm, S Witt, S Richter, M Klein, H Schütze, T W Mühleisen, S Cichon, M Rietschel, M M Noethen, H Tost, E D Gundelfinger, E Düzel, A Heinz, A Meyer-Lindenberg, C I Seidenbecher, H Walter
Recent genome-wide association studies have pointed to single-nucleotide polymorphisms (SNPs) in genes encoding the neuronal calcium channel CaV1.2 (CACNA1C; rs1006737) and the presynaptic active zone protein Piccolo (PCLO; rs2522833) as risk factors for affective disorders, particularly major depression. Previous neuroimaging studies of depression-related endophenotypes have highlighted the role of the subgenual cingulate cortex (CG25) in negative mood and depressive psychopathology. Here, we aimed to assess how recently associated PCLO and CACNA1C depression risk alleles jointly affect memory-related CG25 activity as an intermediate phenotype in clinically healthy humans...
March 18, 2014: Translational Psychiatry
Susanne Erk, Andreas Meyer-Lindenberg, David E J Linden, Thomas Lancaster, Sebastian Mohnke, Oliver Grimm, Franziska Degenhardt, Peter Holmans, Andrew Pocklington, Phöbe Schmierer, Leila Haddad, Thomas W Mühleisen, Manuel Mattheisen, Stephanie H Witt, Nina Romanczuk-Seiferth, Heike Tost, Björn H Schott, Sven Cichon, Markus M Nöthen, Marcella Rietschel, Andreas Heinz, Henrik Walter
Variation in the CACNA1C gene has consistently been associated with psychosis in genome wide association studies. We have previously shown in a sample of n=110 healthy subjects that carriers of the CACNA1C rs1006737 risk variant exhibit hippocampal and perigenual anterior cingulate dysfunction (pgACC) during episodic memory recall. Here, we aimed to replicate our results, by testing for the effects of the rs1006737 risk variant in a new large cohort of healthy controls. We furthermore sought to refine these results by identifying the impact of a CACNA1C specific, gene-wide risk score in the absence of clinical pathology...
July 1, 2014: NeuroImage
Susanne Erk, Andreas Meyer-Lindenberg, Phöbe Schmierer, Sebastian Mohnke, Oliver Grimm, Maria Garbusow, Leila Haddad, Lydia Poehland, Thomas W Mühleisen, Stephanie H Witt, Heike Tost, Peter Kirsch, Nina Romanczuk-Seiferth, Björn H Schott, Sven Cichon, Markus M Nöthen, Marcella Rietschel, Andreas Heinz, Henrik Walter
BACKGROUND: Variation in CACNA1C has consistently been associated with psychiatric disease in genome-wide association studies. We have previously shown that healthy carriers of the CACNA1C rs1006737 risk variant exhibit hippocampal and perigenual anterior cingulate (pgACC) dysfunction during episodic memory recall. To test whether this brain systems-level abnormality is a potential intermediate phenotype for psychiatric disorder, we studied unaffected relatives of patients with bipolar disorder, major depression, and schizophrenia...
September 15, 2014: Biological Psychiatry
Bruno Dietsche, Heidelore Backes, Davide Laneri, Thomas Weikert, Stephanie H Witt, Marcella Rietschel, Jens Sommer, Tilo Kircher, Axel Krug
BACKGROUND: Genome-wide association studies have identified the CACNA1C single nucleotide polymorphism (SNP) rs1006737 as one of the most consistent genetic findings as susceptibility locus for major psychiatric disorders. Furthermore, animal and genetic imaging studies have reported strong functional evidence for the association of CACNA1C with learning, memory, neural plasticity, and its association with the hippocampal formation. In the present study we investigated the impact of the CACNA1C SNP rs1006737 on the fractional anisotropy (FA) in the hippocampal formation as well as on verbal learning and memory in healthy individuals...
April 1, 2014: NeuroImage
Axel Krug, Stephanie H Witt, Heidelore Backes, Bruno Dietsche, Vanessa Nieratschker, N Jon Shah, Markus M Nöthen, Marcella Rietschel, Tilo Kircher
The alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene is one of the best replicated susceptibility loci for bipolar disorder, schizophrenia and major depression. It is involved in learning, memory and brain plasticity. Genetic studies using functional magnetic resonance imaging (fMRI) reported evidence of association with the CACNA1C single nucleotide polymorphism rs1006737 with functional correlates of episodic memory encoding and retrieval, especially activations in the hippocampus...
March 2014: European Archives of Psychiatry and Clinical Neuroscience
Carrie Wright, Jessica A Turner, Vince D Calhoun, Nora Perrone-Bizzozero
The significant impact of microRNAs (miRNAs) on disease pathology is becoming increasingly evident. These small non-coding RNAs have the ability to post-transcriptionally silence the expression of thousands of genes. Therefore, dysregulation of even a single miRNA could confer a large polygenic effect. Schizophrenia is a genetically complex illness thought to involve multiple genes each contributing a small risk. Large genome-wide association studies identified miR-137, a miRNA shown to be involved in neuronal maturation, as one of the top risk genes...
2013: Frontiers in Genetics
Frieder M Paulus, Johannes Bedenbender, Sören Krach, Martin Pyka, Axel Krug, Jens Sommer, Miriam Mette, Markus M Nöthen, Stephanie H Witt, Marcella Rietschel, Tilo Kircher, Andreas Jansen
BACKGROUND: Genome-wide association studies have identified the rs1006737 single nucleotide polymorphism (SNP) in the CACNA1C gene as a susceptibility locus for schizophrenia and bipolar disorder. On the neural systems level this association is explained by altered functioning of the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF), brain regions also affected by mental illness. In the present study we investigated the association of rs1006737 genotype with prefrontal activation and fronto-hippocampal connectivity...
April 2014: Human Brain Mapping
Hiroaki Hori, Noriko Yamamoto, Takashi Fujii, Toshiya Teraishi, Daimei Sasayama, Junko Matsuo, Yumiko Kawamoto, Yukiko Kinoshita, Miho Ota, Kotaro Hattori, Masahiko Tatsumi, Kunimasa Arima, Hiroshi Kunugi
Recent genetic association studies have identified the A-allele of rs1006737 within CACNA1C as a risk factor for schizophrenia as well as mood disorders. Some evidence suggests that this polymorphism plays a role in cognitive function both in schizophrenia patients and healthy individuals; however, the precise nature of this association remains unclear. Here we investigated the possible association of this polymorphism with a wide range of neurocognitive functions in schizophrenia patients and in healthy subjects...
2012: Scientific Reports
Qiumei Zhang, Qiuge Shen, Zhansheng Xu, Min Chen, Lina Cheng, Jinguo Zhai, Huang Gu, Xin Bao, Xiongying Chen, Keqin Wang, Xiaoxiang Deng, Feng Ji, Chuanxin Liu, Jun Li, Qi Dong, Chuansheng Chen
CACNA1C gene polymorphism (rs1006737) is a susceptibility factor for both schizophrenia (SCZ) and bipolar disorder (BP). However, its role in working memory, a cognitive function that is impaired in both diseases, is not clear. Using three samples, including healthy controls, patients with SCZ, and patients currently in manic episodes of BP, this study tested the association between the SNP rs1006737 and spatial working memory as measured by an N-back task and a dot pattern expectancy (DPX) task. Among SCZ patients and healthy controls, the clinical risk allele was associated with impaired working memory, but the association was either in opposite direction or non-significant in patients with BP...
February 2012: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Susanne Erk, Andreas Meyer-Lindenberg, Knut Schnell, Carola Opitz von Boberfeld, Christine Esslinger, Peter Kirsch, Oliver Grimm, Claudia Arnold, Leila Haddad, Stephanie H Witt, Sven Cichon, Markus M Nöthen, Marcella Rietschel, Henrik Walter
CONTEXT: The neural abnormalities underlying genetic risk for bipolar disorder, a severe, common, and highly heritable psychiatric condition, are largely unknown. An opportunity to define these mechanisms is provided by the recent discovery, through genome-wide association, of a single-nucleotide polymorphism (rs1006737) strongly associated with bipolar disorder within the CACNA1C gene, encoding the alpha subunit of the L-type voltage-dependent calcium channel Ca(v)1.2. OBJECTIVE: To determine whether the genetic risk associated with rs1006737 is mediated through hippocampal function...
August 2010: Archives of General Psychiatry
Sven Moosmang, Nicole Haider, Norbert Klugbauer, Helmuth Adelsberger, Nicolas Langwieser, Jochen Müller, Michael Stiess, Else Marais, Verena Schulla, Lubica Lacinova, Sandra Goebbels, Klaus-Armin Nave, Daniel R Storm, Franz Hofmann, Thomas Kleppisch
Current knowledge about the molecular mechanisms of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) in the hippocampus and its function for memory formation in the behaving animal is limited. NMDAR-independent LTP in the CA1 region is thought to require activity of postsynaptic L-type voltage-dependent Ca2+ channels (Cav1.x), but the underlying channel isoform remains unknown. We evaluated the function of the Cav1.2 L-type Ca2+ channel for spatial learning, synaptic plasticity, and triggering of learning-associated biochemical processes using a mouse line with an inactivation of the CACNA1C (Cav1...
October 26, 2005: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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