Genetic reduction of noradrenergic function alters social memory and reduces aggression in mice

Marino, Melissa D.; Bourdelat-Parks, Brooke; Liles, L. Cameron; Weinshenker, David

doi:10.1016/j.bbr.2005.02.005

Cited by 113 publications

(84 citation statements)

References 52 publications

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“…NE released from fibers arising in the locus ceruleus initiates fight-or-flight responses. NE depletion reduces anxiety-related behavior in the plus maze in rats (Lapiz et al, 2001), and mice lacking NE show similar trends in the plus maze and the light-dark box (Marino et al, 2005). 5-HT depletion also reduces anxiety-related behavior in rodents in the elevated plus maze (Treit et al, 1993b) and the light-dark box (Artaiz et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Behavioral and Neurochemical Alterations in Mice Lacking the RNA-Binding Protein Translin

Stein¹,

Bergman²,

Fang³

et al. 2006

J. Neurosci.

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Synapse-specific local protein synthesis is thought to be important for neurodevelopment and plasticity and involves neuronal RNAbinding proteins that regulate the transport and translation of dendritically localized transcripts. The best characterized of these RNAbinding proteins is the fragile X mental retardation protein (FMRP). Mutations affecting the expression or function of FMRP cause fragile X syndrome in humans, and targeted deletion of the gene encoding FMRP results in developmental and behavioral alterations in mice. Translin is an RNA-binding protein that regulates mRNA transport and translation in mouse male germ cells and is proposed to play a similar role in neurons. Like FMRP, translin is present in neuronal dendrites, binds dendritically localized RNA, and associates with microtubules and motor proteins. We reported previously the production of viable homozygous translin knock-out mice, which demonstrate altered expression of multiple mRNA transcripts in the brain and mild motor impairments. Here, we report that translin knock-out mice also exhibit sex-specific differences in tests of learning and memory, locomotor activity, anxiety-related behavior, and sensorimotor gating, as well as handling-induced seizures and alterations in monoamine neurotransmitter levels in several forebrain regions. Similar behavioral and neurochemical alterations have been observed in mice lacking FMRP, suggesting that both proteins may act within the same neuronal systems and signaling pathways. Our results in mice indicate that mutations in translin may contribute to fragile X-like syndromes, mental retardation, attention deficit hyperactivity disorder, epilepsy, and autism spectrum disorders in humans.

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Section: Discussionmentioning

confidence: 99%

Behavioral and Neurochemical Alterations in Mice Lacking the RNA-Binding Protein Translin

Stein¹,

Bergman²,

Fang³

et al. 2006

J. Neurosci.

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“…Dbh −/− mice were bred as described and maintained on a mixed C57BL6/J and 129SvEv genetic background . Dbh +/− mice have normal brain NE content and are behaviorally indistinguishable from wild-type mice, and were used as controls Szot et al, 1999;Marino et al, 2005). Because complete NE deficiency is lethal embryonically in mice (Thomas et al, 1995), NE was restored to knockout embryos by supplementing the drinking water of pregnant dams with adrenergic agonists from E 9.5 to E 14.5, and L-3,4-dihydroxyphenylserine (DOPS) from E 14.5 until birth (Thomas et al, 1995;.…”

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confidence: 99%

“…However, it is not known whether NE depletion affects the basic physiological properties of NE or DA neurons. Dopamine β-hydroxylase knockout (Dbh −/−) mice completely lack NE and have many brainmediated behavioral abnormalities, including impaired maternal and social behavior, defects in memory retrieval, increased seizure susceptibility, dysregulation of DA signaling, and hypersensitivity to psychostimulants (Thomas et al, 1995;Szot et al, 1999;Murchison et al, 2004;Marino et al, 2005;Schank et al, 2005). NE neurons are intact and make proper connections in Dbh −/− mice, and receptor levels and co-transmitter expression are remarkably normal (Weinshenker et al, 2002b;Jin et al, 2004;Sanders et al, in press; D. Weinshenker unpublished observations).…”

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confidence: 99%

Electrophysiological properties of catecholaminergic neurons in the norepinephrine-deficient mouse

Paladini

Beckstead

2007

Neuroscience

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To determine how norepinephrine affects the basic physiological properties of catecholaminergic neurons, brain slices containing the Substantia Nigra Pars Compacta and Locus Coeruleus were studied with cell-attached and whole-cell recordings in control and dopamine β-hydroxylase knockout (Dbh −/−) mice that lack norepinephrine. In the cell-attached configuration, the spontaneous firing rate and pattern of Locus Coeruleus neurons recorded from Dbh −/− mice was the same as the firing rate and pattern recorded from heterozygous littermates (Dbh +/−). During whole-cell recordings, synaptic stimulation produced an α-2 receptor-mediated outward current in the Locus Coeruleus of control mice that was absent in Dbh −/− mice. Normal α-2 mediated outward currents were restored in Dbh −/− slices after pre-incubation with norepinephrine. Locus Coeruleus neurons also displayed similar changes in holding current in response to bath application of norepinephrine, UK 14304, and methionine-enkephalin. Dopamine neurons recorded in the Substantia Nigra Pars Compacta similarly showed no differences between slices harvested from Dbh −/− and control mice. These results indicate that endogenous norepinephrine is not necessary for the expression of catecholaminergic neuron firing properties or responses to direct agonists, but is necessary for auto-inhibition mediated by indirect α-2 receptor stimulation. Keywordsdopamine β-hydroxylase knockout; locus coeruleus; substantia nigra pars compacta; cocaine The activity of norepinephrine (NE) neurons in the locus coeruleus (LC) has an important role in selective attention, general arousal, and stress reactions upon challenging environmental situations (Foote et al., 1983;Levine et al., 1990;Berridge and Waterhouse, 2003;Aston-Jones and Cohen, 2005), and NE depletion may underlie some affective disorders and disease states (Ressler and Nemeroff, 1999). In addition, the LC projects directly to, and modulates the activity of, midbrain dopamine (DA) neurons (Swanson and Hartman, 1975;Jones and Moore, 1977;Liprando et al., 2004), which are critical for reward and motor related behaviors (Girault and Greengard, 2004;Montague et al., 2004). In an intact animal, NE neurons recorded in vitro fire spontaneously in a single-spike Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. pattern at a rate of up to 5 spikes per second (Williams et al., 1984). However, it is not known whether NE depletion affects the basic physiological properties of NE or DA neurons. NIH Public AccessDopamine β-hydroxylase knockout (Dbh −/−) mice completely lack NE and have many bra...

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“…Much less is known about the specific involvement of norepinephrine (NE) and, notably, dopamine (DA) and serotonin (5-HT) in social memory. Disruption of the noradrenergic system has been shown to impair social recognition (Marino et al, 2005;Griffin and Taylor, 1995), whereas the administration of an ␣2-adrenergic antagonist (which increases NE concentrations) has been shown to improve social recognition (Griffin and Taylor, 1995). DA has also been found to facilitate the modulation of social recognition.…”

Section: Oxytocin and Social Recognitionmentioning

confidence: 99%

Social memories in rodents: Methods, mechanisms and modulation by stress

Kooij

Sandi

2012

Neuroscience & Biobehavioral Reviews

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a b s t r a c tIntact social memory forms the basis of meaningful interactions between individuals. Many factors can modulate the quality of social memory, and these have been studied in detail in rodents. Social memory, however, cannot be considered a single entity. The term social memory reflects different processes, such as social recognition of a novel conspecific individual and social learning (or 'learning from others'). This review summarizes the findings obtained with behavioral paradigms that were developed for the study of memory formation by social recognition and social learning. In particular, we focus on studies that include tests for social habituation/discrimination paradigms, tests for memory of a previously established social hierarchy and the social transmission of the food preference test. The role of individual differences and the main neurobiological mechanisms (i.e., the brain regions and neurochemical systems involved) that have been implicated in each of these types of social-related memories are reviewed. In addition, we address the key modulatory influence of stress on the formation of these types of memories; discussing the contribution of central (corticotropin-releasing factor, CRF) and peripheral (glucocorticoids) stress systems and their interactions with the social neuropeptide systems. Overall, we present here a general overview of the current state of a thriving research area within the field of social neuroscience.

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Genetic reduction of noradrenergic function alters social memory and reduces aggression in mice

Cited by 113 publications

References 52 publications

Behavioral and Neurochemical Alterations in Mice Lacking the RNA-Binding Protein Translin

Behavioral and Neurochemical Alterations in Mice Lacking the RNA-Binding Protein Translin

Electrophysiological properties of catecholaminergic neurons in the norepinephrine-deficient mouse

Social memories in rodents: Methods, mechanisms and modulation by stress

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