Enrichment and Training Improve Cognition in Rats with Cortical Malformations

Jenks, Kyle; Lucas, Marcella M.; Duffy, Ben A.; Robbins, Ashlee; Gimi, Barjor; Barry, Jeremy M.; Scott, Rod C.

doi:10.1371/journal.pone.0084492

Cited by 31 publications

(36 citation statements)

References 33 publications

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“…The ELS animals exhibit a less efficient strategy as they had a higher probability of being rotated into the shock zone the more time they spend next to it. Remarkably, our group has reported a similar result in an animal model of cortical dysplasia [44]. …”

Section: 0 Discussionsupporting

confidence: 63%

Spatial cognition following early-life seizures in rats: Performance deficits are dependent on task demands

Barry

Tian

Spinella

et al. 2016

Epilepsy & Behavior

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Cognitive impairment is a common co-morbidity in childhood epilepsy. Studies in rodents have demonstrated that frequent seizures during the first weeks of life results in impaired spatial cognition when the rats are tested as juvenile or adults. To determine if spatial cognitive deficits following early-life seizures are task-specific or similar across spatial tasks we compared the effects of early-life seizures in two spatial assays: 1) The Morris water maze, a hippocampal-dependent task of spatial cognition; and 2) The active avoidance task, a task that associates an aversive shock stimulus with a static spatial location that requires intact hippocampal-amygdala networks. Rats with early-life seizures tested as adults did not differ from control rats in the water maze. However, while animals with early-life seizures showed some evidence of learning the active avoidance task, they received significantly more shocks in later training trials, particularly during the second training day, than controls. One possibility for the performance differences between the tasks is that the active avoidance task requires multiple brain regions and that inter-regional communication could be affected by alterations in white matter integrity. However, there were no measurable group differences with regard to levels of myelination. The study suggests that elucidation of mild cognitive deficits seen following early-life seizures may be dependent on task features of active avoidance.

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Section: 0 Discussionsupporting

confidence: 63%

Spatial cognition following early-life seizures in rats: Performance deficits are dependent on task demands

Barry

Tian

Spinella

et al. 2016

Epilepsy & Behavior

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“…Methylazoxymethanol administered to pregnant dams at E17 results in a bilateral malformation of hippocampal pyramidal cells seen as dispersion of CA1 and CA3 layers (ChevassusAu-Louis et al 1999;Lucas et al 2011). The animals with MCD display abnormalities in cognitive tasks including the Morris water maze and in a place-avoidance task (Lucas et al 2011;Jenks et al 2013;Snyder et al 2013). Both of these tasks are hippocampal dependent.…”

Section: Structural Etiologymentioning

confidence: 99%

“…Unfortunately, many etiologies are considered to be fixed (e.g., hippocampal neuronal loss in temporal lobe epilepsy and MCD) and, therefore, untreatable. However, in animal models of MCDs, it is clear that modification of environments and overtraining paradigms result in dramatic improve-ments in cognitive abilities (Jenks et al 2013). Thus, even though the structural malformation is unchanged, there has been some alteration in functional networks allowing improved performance.…”

Section: Structural Etiologymentioning

confidence: 99%

Mechanisms Responsible for Cognitive Impairment in Epilepsy

Lenck-Santini

Scott

2015

Cold Spring Harb Perspect Med

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Epilepsy is often associated with cognitive and behavioral impairments that can have profound impact on the quality of life of patients. Although the mechanisms of cognitive impairment are not completely understood, we make an attempt to describe, from a systems perspective, how information processing is affected in epilepsy disorders. The aim of this review is to (1) define the nature of cognitive deficits associated with epilepsy, (2) review fundamental systems-level mechanisms underlying information processing, and (3) describe how information processing is dysfunctional in epilepsy and investigate the relative contributions of etiology, seizures, and interictal discharges (IDs). We conclude that these mechanisms are likely to be important and deserve more detailed scrutiny in the future.T he epilepsies are a group of disorders defined by the propensity for an individual to have epileptic seizures (Fisher et al. 2014). In addition to seizures, these common and serious neurological disorders are associated with cognitive and behavioral impairments (Berg and Scheffer 2011). The cognitive and behavioral impairments are critical determinants of the reductions in quality of life observed in patients with epilepsy (Ronen et al. 2003;Loring et al. 2004). It is, therefore, of major importance that the mechanisms underlying cognitive impairments are characterized as this is likely to lead to novel interventions that will ultimately improve the quality of life of people with epilepsy. Epilepsy is associated with a variety of physiological and molecular alterations at the level of changes in the genome, gene expression, receptor characteristics, peptides, and brain injury. These changes are not only responsible for seizures but also for functional abnormalities underlying cognitive impairment. It is likely that several of these mechanisms are occurring in concert, and, therefore, it is important to study the net effects of these alterations at the level of neural networks as this may also lead to novel interventions that could improve outcomes. The aims of this article are to (1) define the nature of cognitive deficits associated with epilepsy, (2) review fundamental systems-level mechanisms underlying information processing, and (3) describe how information processing is dysfunctional in epilepsy and investigate the relative contributions of etiology, seizures, and interictal discharges (IDs).

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“…They hypothesized that it was probably partially instigated by improved mitochondrial function ) and the down-regulation of aquaporin 4 (He, Wang et al 2014). In addition, Jenks et al, (2013) reported improved spatial learning, memory performance and sociability in a rat model displaying severe malformations in cortical development, when the rat pups were raised in a maximally stimulating environment or allowed increased training time. Interestingly, after environmental enrichment, both control and cortical malformation groups outperformed the groups lacking a stimulating environment (Jenks, Lucas et al 2013).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Neuroplasticity and MRI: A perfect match

2016

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Numerous studies have illustrated the benefits of physical workout and cognitive exercise on brain function and structure and, more importantly, on decelerating cognitive decline in old age and promoting functional rehabilitation following injury. Despite these behavioral observations, the exact mechanisms underlying these neuroplastic phenomena remain obscure. This gap illustrates the need for carefully designed in-depth studies using valid models and translational tools which allow to uncover the observed events up to the molecular level. We promote the use of in vivo magnetic resonance imaging (MRI) because it is a powerful translational imaging technique able to extract functional, structural, and biochemical information from the entire brain. Advanced processing techniques allow performing voxel-based analyses which are capable of detecting novel loci implicated in specific neuroplastic events beyond traditional regions-of-interest analyses. In addition, its non-invasive character sets it as currently the best global imaging tool for performing dynamic longitudinal studies on the same living subject, allowing thus exploring the effects of experience, training, treatment etc. in parallel to additional measures such as age, cognitive performance scores, hormone levels, and many others. The aim of this review is (i) to introduce how different animal models contributed to extend the knowledge on neuroplasticity in both health and disease, over different life stages and upon various experiences, and (ii) to illustrate how specific MRI techniques can be applied successfully to inform on the fundamental mechanisms underlying experience-dependent or activity-induced neuroplasticity including cognitive processes.

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Enrichment and Training Improve Cognition in Rats with Cortical Malformations

Cited by 31 publications

References 33 publications

Spatial cognition following early-life seizures in rats: Performance deficits are dependent on task demands

Spatial cognition following early-life seizures in rats: Performance deficits are dependent on task demands

Mechanisms Responsible for Cognitive Impairment in Epilepsy

Neuroplasticity and MRI: A perfect match

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