Lack of the metabotropic glutamate receptor subtype 7 selectively impairs short-term working memory but not long-term memory. Behav Brain Res

Department of Cognitive Neuroscience, University of Tübingen, Auf der Morgenstelle 28, Germany.
Behavioural Brain Research (Impact Factor: 3.03). 11/2004; 154(2):473-81. DOI: 10.1016/j.bbr.2004.03.015
Source: PubMed


Metabotropic glutamate receptors (mGluRs), and in particular the mGluR group III receptors (subtypes 4, 6, 7, 8) are known to play a role in synaptic plasticity and learning. Here, we report the effect of mGluR7 gene ablation in different learning paradigms. In the acoustic startle response (ASR), no differences were seen between knockout (KO) mice and wildtype (WT) littermates in parameters including prepulse inhibition and habituation. In an open field test, no differences were seen between genotypes in motor activity, exploratory behaviour, and fearful behaviour. In a T-maze reinforced alternation working memory (WM) task, again no difference was seen between groups. However, when increasing the demands on working-memory in a 4-arm and 8-arm maze task, KO mice committed more WM errors than WT littermates thereby uncovering a highly significant difference between the two groups that persisted every day for the whole 9 days of the experiment. In a 4-arm maze with 2 arms baited, KO and wildtype mice committed the same number of LTM errors, whereas KOs committed more WM errors. Altogether, these findings suggest that a lack of mGluR7 mainly impairs short-term working but not long-term memory performance while having no effect on sensorimotor processing, non-associative learning, motor activity and spatial orientation. The effects on WM are task-dependent and become apparent in more complex but not simple learning tasks. We discuss how mGluR7 could influence WM.

Download full-text


Available from: Christian Hölscher, Jan 13, 2014
  • Source
    • "ed synaptic plasticity also requires activation of group I mGlus ( Popkirov and Manahan - Vaughan , 2011 ) as do theta - gamma oscillations in the hippocampus ( Bikbaev et al . , 2008 ) . Intriguingly , group II and II mGlu receptors , that are critically required for LTD but not LTP , appear to be highly important for long - term spatial memory ( Holscher et al . , 2004 , 2005 ; Altinbilek and Manahan - Vaughan , 2009 ) that is linked to motivation ( Lyon et al . , 2011b ) . Given recent reports of a role for LTD in spatial context learning ( Kemp and Manahan - Vaughan , 2007 ) , these observations should open up new avenues in the development of strategies to address brain diseases that relate to defi"
    [Show abstract] [Hide abstract]
    ABSTRACT: Storage and processing of information at the synaptic level is enabled by the ability of synapses to persistently alter their efficacy. This phenomenon, known as synaptic plasticity, is believed to underlie multiple forms of long-term memory in the mammalian brain. It has become apparent that the metabotropic glutamate (mGlu) receptor is critically required for both persistent forms of memory and persistent synaptic plasticity. Persistent forms of synaptic plasticity comprise long-term potentiation (LTP) and long-term depression (LTD) that last at least for 4 h but can be followed in vivo for days and weeks. These types of plasticity are believed to be analogous to forms of memory that persist for similar time-spans. The mGlu receptors are delineated into three distinct groups based on their G-protein coupling and agonist affinity and also exercise distinct roles in the way they regulate both long-term plasticity and long-term hippocampus-dependent memory. Here, the mGlu receptors will be reviewed both in general, and in the particular context of their role in persistent (>4 h) forms of hippocampus-dependent synaptic plasticity and memory, as well as forms of synaptic plasticity that have been shown to be directly regulated by memory events. This article is part of a Special Issue entitled 'mGluR'.
    Neuropharmacology 06/2012; 66. DOI:10.1016/j.neuropharm.2012.06.005 · 5.11 Impact Factor
  • Source
    • "Taken together, these data suggest that mGluR7 knockout mice have impaired reference memory acquisition and spatial working memory, and a dysfunctional glutamatergic signalling particularly in the hippocampus and prefrontal cortex where mGluR7 are expressed has been hypothesized to cause these deficits. Performances in complex working memory tasks such as 8-arm radial maze task were also impaired in mGluR7 knockout mice [133]. Interestingly, the working memory deficit was associated with an increased hippocampal theta power while performing the task, which was suggested to reflect a lack of modulation of local inhibition, in turn leading to decreased neuronal firing threshold and altered spike timing [134]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS) and is a major player in complex brain functions. Glutamatergic transmission is primarily mediated by ionotropic glutamate receptors, which include NMDA, AMPA and kainate receptors. However, glutamate exerts modulatory actions through a family of metabotropic G-protein-coupled glutamate receptors (mGluRs). Dysfunctions of glutamatergic neurotransmission have been implicated in the etiology of several diseases. Therefore, pharmacological modulation of ionotropic glutamate receptors has been widely investigated as a potential therapeutic strategy for the treatment of several disorders associated with glutamatergic dysfunction. However, blockade of ionotropic glutamate receptors might be accompanied by severe side effects due to their vital role in many important physiological functions. A different strategy aimed at pharmacologically interfering with mGluR function has recently gained interest. Many subtype selective agonists and antagonists have been identified and widely used in preclinical studies as an attempt to elucidate the role of specific mGluRs subtypes in glutamatergic transmission. These studies have allowed linkage between specific subtypes and various physiological functions and more importantly to pathological states. This article reviews the currently available knowledge regarding the therapeutic potential of targeting mGluRs in the treatment of several CNS disorders, including schizophrenia, addiction, major depressive disorder and anxiety, Fragile X Syndrome, Parkinson's disease, Alzheimer's disease and pain.
    DNA research: an international journal for rapid publication of reports on genes and genomes 03/2012; 10(1):12-48. DOI:10.2174/157015912799362805 · 3.05 Impact Factor
  • Source
    • "Both, mGluR1 and mGluR7 exhibit a somatodendritic localization in Purkinje neurones (Phillips et al. 1998, Martin et al. 1992). However, mutant mice that are deficient for mGluR7 do not exhibit alterations in sensorimotor processing (Holscher et al. 2004). The role of mGluR7 for cerebellar function is therefore still largely unknown. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The metabotropic glutamate receptors type 1 (mGluR1s) are required for a normal function of the mammalian cerebellum. These G-protein-coupled receptors are abundantly expressed in the principle cerebellar cells, namely the Purkinje neurones. Under physiological conditions, mGluR1s are activated during repetitive activity of both afferent glutamatergic synaptic inputs provided by the climbing and parallel fibres respectively. Unlike the common ionotropic glutamate receptors that underlie rapid synaptic excitation, mGluR1s produce a complex post-synaptic response consisting of a Ca2+-release signal from intracellular stores and a slow excitatory post-synaptic potential. While it is well established that the mGluR1-dependent Ca2+-release signal from intracellular stores involves the activation of inositol-trisphosphate receptors, the mechanisms underlying the slow synaptic excitation remained unclear. Here we will review recent evidence indicating an essential role of C-type transient receptor potential (TRPC) cation channels, especially that of the subunit TRPC3, for the generation of the mGluR1-dependent synaptic current. For the signalling pathways underlying both, Ca2+-release from intracellular stores and the slow synaptic potential, we present current knowledge about the activators, downstream effectors and possible roles for mGluR1-dependent signalling in Purkinje neurones.
    Acta Physiologica 10/2008; 195(1):79 - 90. DOI:10.1111/j.1748-1716.2008.01923.x · 4.38 Impact Factor
Show more