Altered prepulse inhibition in rats treated prenatally with the antimitotic Ara-C: an animal model for sensorimotor gating deficits in schizophrenia

Elmer, Gregory I.; Sydnor, James; Guard, H.; Hercher, E.; Vogel, Michael W.

doi:10.1007/s00213-003-1757-7

Cited by 20 publications

(11 citation statements)

References 63 publications

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“…To address the possibility that axons of mature DGCs are competing with axons of young neurons during refinement, we suppressed neurogenesis in the DG of DG-A::TeTxLC-tau-lacZ mice by injecting the anti-mitotic reagent cytosine arabinoside (AraC) intracerebroventricularly (Elmer et al, 2004; Kokoeva et al, 2005) or intraperitoneally from P15 to P22 and examined the elimination of TeTxLC-expressing axons. Intraperitoneal AraC injections effectively blocked neurogenesis in the DG as shown by the disappearance of Ki67-positive cells from the DGC layer (Figure S4A) and the decrease in the number of NeuN-negative young neurons in the DGC layer (Figure S4B).…”

Section: Resultsmentioning

confidence: 99%

Multiple Forms of Activity-Dependent Competition Refine Hippocampal Circuits In Vivo

Yasuda

Johnson-Venkatesh

Zhang

et al. 2011

Neuron

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SUMMARY Efficient memory formation relies on the establishment of functional hippocampal circuits. It has been proposed that synaptic connections are refined by neural activity to form functional brain circuitry. However, it is not known whether and how hippocampal connections are refined by neural activity in vivo. Using a mouse genetic system in which restricted populations of neurons in the hippocampal circuit are inactivated, we show that inactive axons are eliminated after they develop through a competition with active axons. Remarkably, in the dentate gyrus, which undergoes neurogenesis throughout life, axon refinement is achieved by a competition between mature and young neurons. These results demonstrate that activity-dependent competition plays multiple roles in the establishment of functional memory circuits in vivo.

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Section: Resultsmentioning

confidence: 99%

Multiple Forms of Activity-Dependent Competition Refine Hippocampal Circuits In Vivo

Yasuda

Johnson-Venkatesh

Zhang

et al. 2011

Neuron

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“…Prenatal exposure to the antimitotic drug, cytosine arabinoside (Ara-C), produced postpubertal deficits in PPI and disorganization in hippocampal pyramidal cell layers (125). Prenatal exposure to the mitotic inhibitor, methylazoxymethanol (MAM), produced increased amphetamine-induced locomotor activity, deficits in social interaction, impairments in set-shifting tasks, and deficits in radial arm maze performance (126–128).…”

Section: Neurodevelopmental Animal Models Of Schizophreniamentioning

confidence: 99%

Neurodevelopmental Animal Models of Schizophrenia: Role in Novel Drug Discovery and Development

Wilson

Terry

2010

Clinical Schizophrenia & Related Psychoses

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Schizophrenia is a devastating mental illness that is associated with a lifetime of disability. For patients to successfully function in society, the amelioration of disease symptoms is imperative. The recently published results of two large antipsychotic clinical trials (e.g., CATIE, CUtLASS) clearly exemplified the limitations of currently available treatment options for schizophrenia, and further highlighted the critical need for novel drug discovery and development in this field. One of the biggest challenges in schizophrenia-related drug discovery is to find an appropriate animal model of the illness so that novel hypotheses can be tested at the basic science level. A number of pharmacological, genetic, and neurodevelopmental models have been introduced; however, none of these models has been rigorously evaluated for translational relevance or to satisfy requirements of “face,” “construct” and “predictive” validity. Given the apparent polygenic nature of schizophrenia and the limited translational significance of pharmacological models, neurodevelopmental models may offer the best chance of success. The purpose of this review is to provide a general overview of the various neurodevelopmental models of schizophrenia that have been introduced to date, and to summarize their behavioral and neurochemical phenotypes that may be useful from a drug discovery and development standpoint. While it may be that, in the final analysis, no single animal model will satisfy all the requirements necessary for drug discovery purposes, several of the models may be useful for modeling various phenomenological and pathophysiological components of schizophrenia that could be targeted independently with separate molecules or multi-target drugs.

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“…Pre-pubertal adolescent rats display similar startle reactivity (Brunell and Spear 2006;Le Pen et al 2006) and habituation (Elmer et al 2004), but reduced PPI (Brunell and Spear 2006;Elmer et al 2004;Le Pen et al 2006), when compared to adult animals. Yet, an extensive investigation of startle behaviors across adolescence is still lacking.…”

Section: Introductionmentioning

confidence: 96%

Strain-Dependent Changes in Acoustic Startle Response and its Plasticity Across Adolescence in Mice

Pietropaolo

Crusio

2009

Behav Genet

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Acoustic startle response and its plasticity, e.g., habituation and prepulse inhibition (PPI), have been extensively investigated, being altered in several neuropsychiatric disorders. Yet, little is known about the expression of startle-related behaviors during adolescence, a critical phase in the development of a variety of major neuropsychiatric pathologies. The present study investigated for the first time startle behaviors across adolescence in male mice of the inbred strains C57BL/6J and DBA/2J. Pre-pubertal (4 weeks of age) mice displayed reduced startle reactivity and altered PPI compared to adult animals (8 weeks of age), but these effects were observed only in the C57BL/6J strain. Strain differences were also clearly detected for startle response, habituation, and PPI. All effects were modulated by the intensity of the pulse stimulus and were not confounded by differences in anxiety levels. Our data demonstrate that genetic factors and the early adolescent phase are critically important considerations in the design of mouse models of neuropsychiatric disturbances.

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Altered prepulse inhibition in rats treated prenatally with the antimitotic Ara-C: an animal model for sensorimotor gating deficits in schizophrenia

Cited by 20 publications

References 63 publications

Multiple Forms of Activity-Dependent Competition Refine Hippocampal Circuits In Vivo

Multiple Forms of Activity-Dependent Competition Refine Hippocampal Circuits In Vivo

Neurodevelopmental Animal Models of Schizophrenia: Role in Novel Drug Discovery and Development

Strain-Dependent Changes in Acoustic Startle Response and its Plasticity Across Adolescence in Mice

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