Neonatal monoaminergic depletion in mice (Mus musculus) improves performance of a novel odor discrimination task.

Berger-Sweeney, Joanne; Libbey, Megan; Arters, Jill; Junagadhwalla, Mehnaz; Höhmann, Christine F.

doi:10.1037/0735-7044.112.6.1318

Cited by 30 publications

(18 citation statements)

References 41 publications

(48 reference statements)

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“…We review here data from previously published and ongoing studies that demonstrate that mice depleted of 5-HT after birth display a number of sex-dependent behavioral deficits that suggest a phenotype substantially compatible with the core symptoms of autism [13]. In addition, we demonstrate the selectivity and temporal impact of the neonatal depletion and give preliminary evidence that AMPA receptor development is altered after the neonatal cortical 5-HT depletion.…”

Section: Introductionmentioning

confidence: 74%

“…However, this would stand in clear contradiction to normal odor discrimination performance and even slightly superior performance (compared to vehicle and age matched normal controls) on a delayed non-match to sample odor discrimination task that was displayed by the same 5,7-DHT-lesioned cohort of mice [13]. In the simple odor discrimination task, the mice learned to associate a buried food reward (chocolate chip in a cup of sand) with a particular scent.…”

Section: Behavioral Characterizationmentioning

confidence: 91%

“…Bilateral injections of 5,7-DHT (Sigma-Aldrich; 0.6 microliter of a 5 micogram/microliter solution) or sterile saline (vehicle-injected shams) were made into the mfb as described previously (see Figure 1) [13,60]. Lesion coordinates were as follows: entry of the cannula was at 1mm anterior to the fronto-nasal suture and 1.5 mm lateral to the midline.…”

Section: Animals and Surgerymentioning

confidence: 99%

“…a detailed description of the passive avoidance task, the simple odor discrimination task and the delayed none matched to sample odor discrimination task, please consult our paper by Berger-Sweeney et al [13]. Please note that for these initial studies all mice were raised and tested at Wellesley College in the laboratory of Dr. Berger-Sweeney.…”

Section: Additional Behavioral Tests-formentioning

confidence: 99%

“…Impaired Impulse Inhibition-We have previously published behavioral studies that suggest impaired impulse inhibition in the neonatally lesioned mice [13]. When tested on a passive avoidance task, 5,7-DHT-lesioned males and females acquired this aversively motivated task normally, but when tested 24 hours later, lesioned males, in particular, displayed a significant performance deficit (50% decrease in latency compared to age matched normal and vehicle control males).…”

Section: Behavioral Characterizationmentioning

confidence: 99%

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Modeling early cortical serotonergic deficits in autism

Boylan

Blue

Höhmann

2007

Behavioural Brain Research

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Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro-and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

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Section: Introductionmentioning

confidence: 74%

Section: Behavioral Characterizationmentioning

confidence: 91%

Section: Animals and Surgerymentioning

confidence: 99%

Section: Additional Behavioral Tests-formentioning

confidence: 99%

Section: Behavioral Characterizationmentioning

confidence: 99%

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Modeling early cortical serotonergic deficits in autism

Boylan

Blue

Höhmann

2007

Behavioural Brain Research

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Sexually dimorphic responses to neonatal basal forebrain lesions in mice: I. Behavior and neurochemistry

et al. 1998

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The nucleus basalis magnocellularis (nBM) provides the primary source of cholinergic input to the cortex. Neonatal lesions of the nBM produce transient reductions in cholinergic markers, persistent abnormalities in cortical morphology, and spatial navigation impairments in adult mice. The present study examined sex differences in the effects of an electrolytic nBM lesion on postnatal day 1 (PND 1) in mice on behavior and neurochemistry in adulthood. Mice were lesioned on PND 1 and tested at 8 weeks of age on a battery of behavioral tests including passive avoidance, cued and spatial tasks in the Morris water maze, simple and delayed nonmatch to sample versions of an odor discrimination task, and locomotor activity measurements. Following behavioral testing, mice were sacrificed for either morphological assessment or neurochemical analysis of a cholinergic marker or catecholamines. There were no lesion or sex differences in acquisition or retention of passive avoidance, performance of the odor discrimination tasks, or activity levels. Control mice showed a robust sex difference in performance of the spatial water maze task. The lesion produced a slight cued but more dramatic spatial navigation deficit in the water maze which affected only the male mice. Neurochemical analyses revealed no lesion‐induced changes in either choline acetyltransferase activity or levels of norepinephrine or serotonin at the time of testing. The subsequent report shows a sex difference in lesion‐induced changes in cortical morphology which suggests that sexually dimorphic cholinergic influences on cortical development are responsible for the behavioral deficits seen in this study. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 582–594, 1998

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Sexually dimorphic responses to neonatal basal forebrain lesions in mice: II. Cortical morphology

Höhmann

Berger-Sweeney

1998

J. Neurobiol.

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Previous studies in the mouse have shown that neonatal lesions to the cholinergic basal forebrain (nBM) areas result in transient cholinergic depletion of neocortex and precipitate altered cortical morphogenesis. Lesion‐induced morphological alterations in cortex persist into adulthood and are accompanied by behavioral changes, including spatial memory deficits. The current study investigated whether neonatal nBM lesions affect male and female mice differently in adulthood. Quantitative morphometry of cortical layer width was employed to assess alterations in cytoarchitecture in neonatally nBM‐lesioned and littermate control mice of both sexes following behavioral testing. Our results showed significant decreases in cortical layer IV and V widths across somato/motor cortex in neonatally nBM lesioned mice of both sexes. Sexually dimorphic responses were observed in cortical layer II/III and total cortical width, limited to the area containing the “barrel cortex” representation of the whisker hairs. In lesioned females, layer II/III and total cortical width were decreased relative to female controls, and in lesioned males, layer II/III was increased relative to controls, whereas total cortical width was unchanged. In male but not female mice we observed significant correlations between decreased widths in layer IV and V and impaired performance on a spatial memory task. The current data further support a role of developing cholinergic cortical afferents in the modulation of cortical morphogenesis and cortical circuits involved in cognitive behaviors. In addition, our observations provide further evidence for sexually dimorphic development and function in cognitive centers of the rodent brain. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 595–606, 1998

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Neonatal monoaminergic depletion in mice (Mus musculus) improves performance of a novel odor discrimination task.

Cited by 30 publications

References 41 publications

Modeling early cortical serotonergic deficits in autism

Modeling early cortical serotonergic deficits in autism

Sexually dimorphic responses to neonatal basal forebrain lesions in mice: I. Behavior and neurochemistry

Sexually dimorphic responses to neonatal basal forebrain lesions in mice: II. Cortical morphology

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