Predator odor modulates auditory event-related potentials in mice

SMRI Laboratory for Experimental Therapeutics in Psychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, USA.
Neuroreport (Impact Factor: 1.52). 08/2009; 20(14):1260-4. DOI: 10.1097/WNR.0b013e3283300cde
Source: PubMed

ABSTRACT Animals process information from different sensory modalities, requiring integration of signals and assignment of significance. People with schizophrenia perceive sensory information without external stimuli (hallucinations) and attribute meaning to coincidental events (referential delusions), suggesting deficits in sensory integration. We investigate sensory integration deficits by measuring the impact of olfactory cues on auditory processing in a mouse model of schizophrenia. N-methyl-D-aspartate-NR1 knockdown and wild-type mice were exposed to predator odor during auditory event-related potentials. Both groups reduced N1 event-related potential amplitude in the presence of predator odor, indicating that mice appropriately integrate olfactory and auditory stimuli. NR1 knockdown mice do not have deficits in this task, suggesting that sensory integration may rely on non-N-methyl-D-aspartate receptor mediated circuits.

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Available from: Tobias Halene, Sep 28, 2015
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    • "Here, we demonstrate that auditory function, exploratory ability, and the capacity to vocalize are all intact. Likewise, we and others have previously reported that visual and olfactory function is unaltered in NR1 neo−/− mice, using behavioral and electrophysiological measures (Duncan et al., 2004, Halene et al., 2009b). Pain sensation was shown to be present, and perhaps even enhanced, in a previous study (Bickel et al., 2007). "
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    ABSTRACT: Reduced NMDA-receptor (NMDAR) function has been implicated in the pathophysiology of neuropsychiatric disease, most strongly in schizophrenia but also recently in autism spectrum disorders (ASD). To determine the direct contribution of NMDAR dysfunction to disease phenotypes, a mouse model with constitutively reduced expression of the obligatory NR1 subunit has been developed and extensively investigated. Adult NR1(neo-/-) mice show multiple abnormal behaviors, including reduced social interactions, locomotor hyperactivity, self-injury, deficits in prepulse inhibition (PPI) and sensory hypersensitivity, among others. Whereas such phenotypes have largely been interpreted in the context of schizophrenia, these behavioral abnormalities are rather non-specific and are frequently present across models of diseases characterized by negative symptom domains. This study investigated auditory electrophysiological and behavioral paradigms relevant to autism, to determine whether NMDAR hypofunction may be more consistent with adult ASD-like phenotypes. Indeed, transgenic mice showed behavioral deficits relevant to all core ASD symptoms, including decreased social interactions, altered ultrasonic vocalizations and increased repetitive behaviors. NMDAR disruption recapitulated clinical endophenotypes including reduced PPI, auditory-evoked response N1 latency delay and reduced gamma synchrony. Auditory electrophysiological abnormalities more closely resembled those seen in clinical studies of autism than schizophrenia. These results suggest that NMDAR hypofunction may be associated with a continuum of neuropsychiatric diseases, including schizophrenia and autism. Neural synchrony abnormalities suggest an imbalance of glutamatergic and GABAergic coupling and may provide a target, along with behavioral phenotypes, for preclinical screening of novel therapeutics.
    Genes Brain and Behavior 06/2012; 11(6):740-50. DOI:10.1111/j.1601-183X.2012.00816.x · 3.66 Impact Factor
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    • "However, integration of visual or auditory information with olfactory cues remains largely unstudied. Although evidence for multisensory integration between olfaction and audition is scarce, it is not without precedent (Halene et al., 2009). In addition, recent work showed that the opposite interaction also exists. "
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    ABSTRACT: Motherhood is associated with different forms of physiological alterations including transient hormonal changes and brain plasticity. The underlying impact of these changes on the emergence of maternal behaviors and sensory processing within the mother's brain are largely unknown. By using in vivo cell-attached recordings in the primary auditory cortex of female mice, we discovered that exposure to pups' body odor reshapes neuronal responses to pure tones and natural auditory stimuli. This olfactory-auditory interaction appeared naturally in lactating mothers shortly after parturition and was long lasting. Naive virgins that had experience with the pups also showed an appearance of olfactory-auditory integration in A1, suggesting that multisensory integration may be experience dependent. Neurons from lactating mothers were more sensitive to sounds as compared to those from experienced mice, independent of the odor effects. These uni- and multisensory cortical changes may facilitate the detection and discrimination of pup distress calls and strengthen the bond between mothers and their neonates. VIDEO ABSTRACT:
    Neuron 10/2011; 72(2):357-69. DOI:10.1016/j.neuron.2011.08.019 · 15.05 Impact Factor
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