A transthalamic pathway crucial for perception.

Perception is largely supported by cortical processing that involves communication among multiple areas, typically starting with primary sensory cortex and then involving higher order cortices. This communication is served in part by transthalamic (cortico-thalamo-cortical) pathways, which ubiquitously parallel direct corticocortical pathways, but their role in sensory processing has largely remained unexplored. Here, we suggest that transthalamic processing propagates task-relevant information required for correct sensory decisions.

A Sensorimotor Pathway via Higher-Order Thalamus.

We now know that sensory processing in cortex occurs not only via direct communication between primary to secondary areas, but also via their parallel cortico-thalamo-cortical (i.e., -thalamic) pathways.

Synaptic properties of the lemniscal and paralemniscal pathways to the mouse somatosensory thalamus.

Somatosensory information is thought to arrive in thalamus through two glutamatergic routes called the lemniscal and paralemniscal pathways via the ventral posterior medial (VPm) and posterior medial (POm) nuclei. Here we challenge the view that these pathways functionally represent parallel information routes. Using electrical stimulation and an optogenetic approach in brain slices from the mouse, we investigated the synaptic properties of the lemniscal and paralemniscal input to VPm and POm.

What's wrong with my mouse cage? Methodological considerations for modeling lifestyle factors and gene-environment interactions in mice.

The mechanistic understanding of lifestyle contributions to disease has been largely driven by work in laboratory rodent models using environmental interventions. These interventions show an array of methodologies and sometimes unclear collective conclusions, hampering clinical interpretations. Here we discuss environmental enrichment, exercise and stress interventions to illustrate how different protocols can affect the interpretations of environmental factors in disease.

Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease.

Unlike many other neurodegenerative diseases with established gene-environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions.

'Super-Enrichment' Reveals Dose-Dependent Therapeutic Effects of Environmental Stimulation in a Transgenic Mouse Model of Huntington's Disease.

Background: Huntington's disease (HD) is caused by a tandem repeat expansion and involves progressive cognitive decline, psychiatric abnormalities and motor deficits. Disease onset and progression in HD mice can be substantially delayed by a housing environment with enhanced sensorimotor and cognitive stimulation. However, the proposed benefits of environmental enrichment (EE) are always taken in the context of 'deprived' standard housing and investigation is warranted into the graded effects of enrichment.

Ethological endophenotypes are altered by elevated stress hormone levels in both Huntington's disease and wildtype mice.

Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder with cognitive, psychiatric, motor, neuroendocrine and peripheral dysfunctions. Symptom onset and progression can be closely modeled in HD transgenic mice, which facilitate the search for therapeutics and environmental modulators. In the first investigation of chronic stress in HD, we have previously shown that administering a moderate dose of the stress hormone, corticosterone (CORT) had no effect on short-term memory in wildtype (WT) mice but accelerated the onset of the impairment in male R6/1 HD mice.

Effects of chronic stress on the onset and progression of Huntington's disease in transgenic mice.

Huntington's disease (HD) is a neurodegenerative disease caused by a tandem repeat mutation encoding an expanded polyglutamine tract. Our previous work showed that memory deficits in HD transgenic mice could be accelerated by increased levels of stress hormone, while memory in WT mice remained unaffected. HD patients experience higher levels of stress compared to the general population and symptoms of HD also include motor, cognitive, psychiatric, sexual and olfactory abnormalities, and an associated decline in activities of daily living.

High stress hormone levels accelerate the onset of memory deficits in male Huntington's disease mice.

Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat mutation in the huntingtin gene. Lifestyle factors, such as lack of activity may contribute to the variability in the age of disease onset. Therefore, better understanding of environmental modifiers may uncover potential therapeutic approaches to delay disease onset and progression.

Novel ethological endophenotypes in a transgenic mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder with a characteristic triad of cognitive, affective and motor symptoms. Transgenic HD mice show excellent construct and face validity for many of these symptoms, however the decline in some facets of every day activity in humans is difficult to model. One approach is the assessment of species-relevant behaviors.

Short-term memory acquisition in female Huntington's disease mice is vulnerable to acute stress.

Huntington's disease (HD) is a neurodegenerative disorder marked by cognitive, psychiatric and motor decline, and is modifiable by unidentified environmental factors. We examined the effects of stress on cognitive function in R6/1 HD transgenic mice. Utilizing the Y-maze to assess short-term memory, we report that only female HD mice displayed vulnerability to 1h of confinement stress reflected by impaired memory acquisition.

Differential effects of early environmental enrichment on emotionality related behaviours in Huntington's disease transgenic mice.

Psychiatric disorders such as depression and anxiety are reported in patients with Huntington's disease (HD). Recent studies suggest beneficial effects of environmental enrichment (EE) on HD progression possibly through the serotonergic system. We investigated the potential effectiveness of EE in correcting the affective-like phenotype of female R6/1 HD mice.

Transcranial pulsed magnetic field stimulation facilitates reorganization of abnormal neural circuits and corrects behavioral deficits without disrupting normal connectivity.

Although the organization of neuronal circuitry is shaped by activity patterns, the capacity to modify and/or optimize the structure and function of whole projection pathways using external stimuli is poorly defined. We investigate whether neuronal activity induced by pulsed magnetic fields (PMFs) alters brain structure and function. We delivered low-intensity PMFs to the posterior cranium of awake, unrestrained mice (wild-type and ephrin-A2A5(-/-)) that have disorganized retinocollicular circuitry and associated visuomotor deficits.