Monday, April 17, 2017

Improving localization using Buresova's on-demand platform.


Over 20 years ago Buresova discovered that it was possible to significantly improved localization of rats by training with a collapsible and previously hidden platform that emerges when the rat passes over it. Variations on this have become known as the Atlantis platform and it now forms a key way of differentiating or sharpening results where there experimenter is worried that the changes or effects between control and experimental groups might be small. This is extremely valuable in cases where identifying the differences between control and test animals in crucial and worth a small additional investment. Things to check for in the modern Atlantis platform include (1) silent operation (which is often not the case with pump driven pneumatic ones - which give a directional auditory cue from the pump motor, (2) complete electrical isolation from the mains (which is essential given that the experimenter is operating in water) and (3) the availability of Atlantis arrays so that the platform does not have to be repositioned between trials, but instead the array comprises four different platforms any one of which can be operated separately by the controller. The best systems today are the Neodymium Iron Boron actuators (AKA "Neo" or NdFeB) which actually hold the platform in place with no current flow and only need a current pulse of a few milliseconds to release. These are safer, more quiet and much faster in operation and represent a really worthwhile move forward from systems of five years ago or more.

Rats trained with the Atlantis platform show improved spatial localization of search
Figure from Spooner et al 1995


Wednesday, April 12, 2017

How to run water maze on humans - and how not to.

Virtual water maze tasks have been around for many years now (e.g.
Sandstrom et al 1998), but if you've experienced actual virtual reality versions rather than ersatz versions you'll appreciate that there is a huge difference which can be quantified in terms of hippocampal theta activity (Cornwell et al 2008).  There is a good description of why these differences are seen in the Behavioral Neuroscience Tasks in Virtual Reality pages as well as explanations of why what you thought was Virtual Reality in some experiments really isn't and often elicits quite different search strategies from those found both in reality and higher quality representations.

Wednesday, June 22, 2016

USB cameras for tracking in Morris Water Maze and other experiments

A range of USB cameras can be used with the HVS Image video tracking and analysis software, including the HVS Image camera supplied in the accessories kit available from the company, and off-the-shelf web cams you can buy from PC stores or at low cost from eBay and Amazon.

Which camera suits you best will depend on your experimental set-up and whether you need to cater for more than one type of experiment.

If you want a versatile camera that can be used at different distances from the tracking area and for tracking area of different dimensions, the HVS Image camera is the answer. This has:
  • wide angle lens for use with Morris Water Maze, and other lenses for smaller mazes and arenas;
  • manual focus allowing you to focus at the tracking surface, so there is no issue of an auto-focus taking time to adjust when the subject enters the tracking area - it will already be in focus;
  • threaded mounting point for fixing the camera securely in place with the accompanying ceiling mount or other standard mount.
The HVS Image camera comes with a 30 foot USB boosted extension lead, lenses including a wide angle and a varifocal zoom, ceiling mount and long range wireless remote for starting trials from the pool, maze or arena.

Other cameras that can be used include the low cost Microsoft LifeCams such as the VX-800, which you can pick up for around $10, or the Logitech C920. Watch out for the following if choosing your own camera:
  • Not all web cams have a threaded mounting point, so you may need another way to hold it in place, such as duct tape;
  • Most web cams are auto-focus, so run some tests to make sure that the image is clear enough for the subject to be tracked right from the start of the trial;
  • The angle of view stated in web cam specs is usually the diagonal, so be careful to ensure you get one that will fit your tracking area into the image;
  • Most web cams don't have a wide enough angle to fit a large water maze, unless you have a high ceiling, so you may need the HVS Image camera. HVS Image are always happy to advise.

Thursday, June 9, 2016

May 2016, Some Publications using Morris Water Maze


The water maze paradigm in experimental studies of chronic cognitive disorders: Theory, protocols, analysis, and inference

M Kapadia, J Xu, B Sakic 

An instrumental step in assessing the validity of animal models of chronic cognitive disorders is to document disease-related deficits in learning/memory capacity. The water maze (WM) is a popular paradigm because of its low cost, relatively simple protocol and short procedure time. Despite being broadly accepted as a spatial learning task, inference of generalized, bona fide “cognitive” dysfunction can be challenging because task accomplishment is also reliant on non-cognitive processes. We review theoretical background, testing procedures, confounding factors, as well as approaches to data analysis and interpretation. We also describe an extended protocol that has proven useful in detecting early performance deficits in murine models of neuropsychiatric lupus and Alzheimer’s disease. Lastly, we highlight the need for standardization of inferential criteria on “cognitive” dysfunction in experimental rodents and exclusion of preparations of a limited scientific merit. A deeper appreciation for the multifactorial nature of performance in WM may also help to reveal other deficits that herald the onset of neurodegenerative brain disorders.

--

Differences in Behavioral Responding in Adult and Aged Rats Following Chronic Ethanol Exposure

A Novier, LC Ornelas…

Research suggests symptoms of chronic alcoholism, and withdrawal may be more severe in elderly compared with younger adults. However, examination of the effects of long-term ethanol (EtOH) consumption and withdrawal is limited in aged rodents. We thus investigated EtOH withdrawal and potential deficits in cognitive and motor behavior in young adult and aged rats. We also examined the effects of acute allopregnanolone as a potential mechanism contributing to age-related differences in EtOH's cognitive-impairing effects.
--

Treatment of traumatic brain injury in rats with N-acetyl-seryl-aspartyl-lysyl-proline

Y Zhang, ZG Zhang, M Chopp, Y Meng, L Zhang…

The authors' previous studies have suggested that thymosin beta 4 (Tβ4), a major actin-sequestering protein, improves functional recovery after neural injury. N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an active peptide fragment of Tβ4. Its effect as a treatment of traumatic brain injury (TBI) has not been investigated. Thus, this study was designed to determine whether AcSDKP treatment improves functional recovery in rats after TBI.

April 2016, Publications using Morris Water Maze


Morin reverses neuropathological and cognitive impairments in APPswe/PS1dE9 mice by targeting multiple pathogenic mechanisms

Y Du, J Qu, W Zhang, M Bai, Q Zhou, Z Zhang, Z Li…

Keywords
Alzheimer's disease; Amyloid-beta protein; Tau phosphorylation; Neuroinflammation; Cognitive deficits; Morin

Abstract
Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by progressive cognitive impairment and multiple distinct neuropathological features. Currently, there are no available therapies to delay or block the disease progression. Thus, the disease-modifying therapies are urgent for this devastating disorder by simultaneously targeting multiple distinct pathological processes. Morin, a natural bioflavonoid, have been shown to be strongly neuroprotective in vitro and in vivo. In this study, we first investigated the disease-modifying effects of chronic morin administration on the neuropathological and cognitive impairments in APPswe/PS1dE9 double transgenic mice. Our results showed that chronic morin administration prevented spatial learning and memory deficits in the APPswe/PS1dE9 mice. Morin treatment in the APPswe/PS1dE9 mice markedly reduced cerebral Aβ production and Aβ plaque burden via promoting non-amyloidogenic APP processing pathway by increasing ADAM10 expression, inhibiting amyloidogenic APP processing pathway by decreased BACE1 and PS1 expression, and facilitating Aβ degradation by enhancing Aβ-degrading enzyme expression. In addition, we also found that morin treatment in the APPswe/PS1dE9 mice markedly decreased tau hyperphosphorylation via its inhibitory effect on CDK5 signal pathway. Furthermore, morin treatment in the APPswe/PS1dE9 mice markedly reduced the activated glial cells and increased the expression of synaptic markers. Collectively, our findings demonstrate that chronic morin treatment restores cognitive functions and reverses multiple distinct neuropathological AD-like hallmarks in the APPswe/PS1dE9 mice. This study provides novel insights into the neuroprotective actions and neurobiological mechanisms of morin against AD, suggesting that morin is a potently promising disease-modifying agent for treatment of AD.

--

Adolescent Choline Supplementation Attenuates Working Memory Deficits in Rats Exposed to Alcohol During the Third Trimester Equivalent

RD Schneider, JD Thomas

Keywords:

  • Fetal Alcohol;
  • Fetal Alcohol Spectrum Disorders;
  • Treatment;
  • Nutrition

Background

Children exposed to alcohol prenatally may suffer from behavioral and cognitive alterations that adversely affect their quality of life. Animal studies have shown that perinatal supplementation with the nutrient choline can attenuate ethanol's adverse effects on development; however, it is not clear how late in development choline can be administered and still effectively reduce the consequences of prenatal alcohol exposure. Using a rodent model, this study examined whether choline supplementation is effective in mitigating alcohol's teratogenic effects when administered during adolescence/young adulthood.

Methods

Sprague–Dawley rats were exposed to alcohol (5.25 g/kg/d) during the third trimester equivalent brain growth spurt, which occurs from postnatal day (PD) 4 to 9, via oral intubation. Sham-intubated and nontreated controls were included. Subjects were treated with 100 mg/kg/d choline chloride or vehicle from PD 40 to 60, a period equivalent to young adulthood in the rat. After the choline treatment had ceased, subjects were tested on a series of behavioral tasks: open field activity (PD 61 to 64), Morris water maze spatial learning (PD 65 to 73), and spatial working memory (PD 87 to 91).

Results

Ethanol-exposed subjects were overactive in the activity chambers and impaired on both the spatial and the working memory versions of the Morris water maze. Choline treatment failed to attenuate alcohol-related overactivity in the open field and deficits in Morris water maze performance. In contrast, choline supplementation significantly mitigated alcohol-related deficits in working memory, which may suggest that choline administration at this later developmental time affects functioning of the prefrontal cortex.

Conclusions

The results indicate that adolescent choline supplementation can attenuate some, but not all, of the behavioral deficits associated with early developmental alcohol exposure. The results of this study indicate that dietary intervention may reduce some fetal alcohol effects, even when administered later in life, findings with important implications for adolescents and young adults with fetal alcohol spectrum disorders.
--

Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin‐1β

S Ekmark‐Lewén, J Flygt…

Keywords:

  • axonal injury;
  • behavioural outcome;
  • central fluid percussion injury;
  • interleukin-1β;
  • traumatic brain injury

Abstract

Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin (IL)-1β has not been established in TAI. An IL-1β-neutralizing or a control antibody was administered intraperitoneally at 30 min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n = 41) were compared with sham-injured controls (n = 20) and untreated, naive mice (n = 9). The anti-IL-1β antibody reached the target brain regions in adequate therapeutic concentrations (up to ~30 μg/brain tissue) at 24 h post-injury in both cFPI (n = 5) and sham-injured (n = 3) mice, with lower concentrations at 72 h post-injury (up to ~18 μg/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9 days post-injury, and the Morris water maze (MWM) at 14–21 days post-injury. Following TAI, the IL-1β-neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL-1β-neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL-1β is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI.

March 2016 - A Few Publications using Morris Water Maze


Glutamatergic and central cholinergic dysfunction in the CA1, CA2 and CA3 fields on spatial learning and memory in chronic cerebral ischemia—Induced vascular …

Y Cao, Z Gou, Y Du, Y Fan, L Liang, Y Yan, P Lin…

Some Morris Water Maze Publications, February 2016


Glutamatergic and central cholinergic dysfunction in the CA1, CA2 and CA3 fields on spatial learning and memory in chronic cerebral ischemia—Induced vascular …

Y Cao, Z Gou, Y Du, Y Fan, L Liang, Y Yan, P Lin…