Neonatal 192 IgG-saporin lesions of basal forebrain cholinergic neurons selectively impair response to spatial novelty in adult rats.

Ricceri, Laura; Usiello, Alessandro; Valanzano, Angela; Calamandrei, Gemma; Frick, Karyn M.; Berger-Sweeney, Joanne

doi:10.1037/0735-7044.113.6.1204

Cited by 47 publications

(32 citation statements)

References 56 publications

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“…Previous work in mice and rats, using paradigms similar to the OFOR task used by us, show that normal rodents habituate to objects, as indicated by a gradual decrease in exploration between S2 and S4; but they increase their exploration in response to spatial object displacement and object novelty (Poucet, 1989;Thinus-Blanc et al, 1996;Ricceri et al, 1999;Frick and Gresack, 2003). To what extent animals increase their exploration of all objects or only that of the displaced objects, relative to the unchanged objects, appears to depend on sex and strain variables (Poucet, 1989;Thinus-Blanc et al, 1996;Frick and Gresack, 2003).…”

Section: Behavioral Effectsmentioning

confidence: 61%

“…Lack of response to spatial change is generally associated with damage to, or abnormalities in, brain centers involved in spatial learning and memory such as the hippocampus and neocortex (Poucet, 1989;Save et al, 1992;Thinus-Blanc et al, 1996;Hohmann et al, 1999;Ricceri et al, 2002). However, the response to object novelty is usually left intact in these paradigms (Save et al, 1992;Ricceri et al, 1999).…”

Section: Behavioral Effectsmentioning

confidence: 99%

“…Object Recognition Task-This task was adapted from a task developed by Ricceri et al (Ricceri et al, 1999) in accordance with parameters introduced by Poucet (Poucet, 1989). The OFOR task was performed in a round enclosure of approximately 3 feet in diameter surrounded by walls of about ten inches in height that lean outward at a slight angle of about 15 degrees (commercial plastic baby pool).…”

Section: Open Fieldmentioning

confidence: 99%

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Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

et al. 2007

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Multiple brain disorders that show serotonergic imbalances have a developmental onset. Experimental models indicate a role for serotonin as a morphogen in brain development. To selectively study the effects of serotonin depletions on cortical structural development and subsequent behavior, we developed a mouse model in which a serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), is injected into the medial forebrain bundle (mfb) on the day of birth. Littermates with saline injections into the mfb and age matched mice served as controls. This study characterized the extent and duration of serotonergic denervation after the selective neonatal lesion and investigated effects on exploratory behavior, spatial learning and anxiety in mice of both sexes. We report significant decreases in the serotonergic (5-HT) innervation to cortex and hippocampus, but not to subcortical forebrain structures in 5,7-DHT-lesioned mice. The depletion of 5-HT fibers in cortical areas was long lasting in lesioned mice but autoradiographic binding to high affinity 5-HT transporters was only transiently reduced. Male but not female lesioned mice reduced their exploration significantly in response to spatial rearrangement and object novelty, suggesting increased anxiety in response to change but normal spatial cognition. Our data show that developmental disruptions in the serotonergic innervation of cortex and hippocampus are sufficient to induce permanent, sex specific, behavioral alterations. These results may have significant implications for understanding brain disorders presenting with cortical morphogenetic abnormalities and altered serotonin neurotransmission, such as autism, schizophrenia and affective disorders.

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Section: Behavioral Effectsmentioning

confidence: 61%

Section: Behavioral Effectsmentioning

confidence: 99%

Section: Open Fieldmentioning

confidence: 99%

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Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

et al. 2007

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“…task was adapted from a task developed by Ricceri et al [100] in accordance with parameters introduced by Poucet [95]. The OFOR task was performed in a round enclosure of approximately 3 feet in diameter, surrounded by walls of about ten inches high that lean outward at a slight angle of about 15 degrees (commercial plastic baby pool).…”

Section: Open Field Object Recognition (Ofor)-thismentioning

confidence: 99%

“…Moreover, change in object positions, after the mice had established a "routine" of exploring the same 5 objects in the same locations for three six minute sessions, resulted in a significant 30% decrease (p=0.024) of all exploratory activity in lesioned male mice. Changing object position is ordinarily used to assess spatial learning and memory and normal mice increase exploration, particularly of the displaced objects [95,100,103]. The results of the OFOR analysis showed that lesioned mice acquired and retained spatial information relatively normally, but had an abnormal response to this challenge that suggested aversion to spatial change.…”

Section: Open Field Object Recognition (Ofor)mentioning

confidence: 99%

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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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

show abstract

Neonatal 192 IgG-saporin lesions of basal forebrain cholinergic neurons selectively impair response to spatial novelty in adult rats.

Cited by 47 publications

References 56 publications

Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

Modeling early cortical serotonergic deficits in autism

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

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