Congratulation to all participants of the symposium for giving great presentation, with special congratulations to the winners:

1st place: Marko Ilievski

2nd place: Rachael Chan

3rd place: Zach Wanner

Honourable mention: Hannah Scott

Abstracts

PATERNAL HEALTH AND DEVELOPMENT

1.
The effect of preconception paternal alcohol consumption on offspring social play

Corbin Chenger, Allona Harker, Sarah Raza, Robbin Gibb

The effects of maternal experience on offspring development are well known. However, there is less awareness on the effects of preconception paternal experience. Most people are aware of quantitative effects on sperm in terms of fertility, but few are aware of qualitative effects that likely occur through epigenetic mechanisms. Recent research in our lab has shown that paternal alcohol does affect neuroanatomy and behavior. As such, we decided to analyze play behavior in rats sired by alcohol-exposed fathers. The findings from this study could be utilized to communicate the importance of preconception paternal health.

Paternal exposure to fluoxetine: Effects on brain, behavior, and the epigenome of offspring

Ana J.C. Carvalho, Allona Harker, Brian Kolb, Robbin Gibb

Fluoxetine (SSRI) is one of the most prescribed antidepressants in the world. Recent studies have shown the influence of fluoxetine in the spermatogenesis of adult male rats, which may lead to reproductive problems. Recently, paternal preconception experience is a topic that has been in the spotlight, as paternal genes have been shown to greatly influence placenta formation. This study proposes to examine the effects of father exposure to fluoxetine on the epigenetic, anatomical, and functional outcomes of the offspring.

Stereological analysis of brain tissue derived from animals with preconception exposure to alcohol

Lindsay Amatto, Marisa Lelekach, Allonna Harker, Sarah Raza, Bryan Kolb, Robbin Gibb

The effect of maternal experience on the prenatal environment is well researched. However, comprehensive examination of father experience is lacking. We examined the effects of paternal preconception alcohol exposure on their offspring through stereological analysis of the AID and Cg3 areas of the prefrontal cortex. We determined that significant differences were noted in the AID areas but no significant findings were observed in the Cg3 areas. These results suggest that paternal alcohol exposure alters brain anatomy in offspring.

TRANSGENERATIONAL PROGRAMMING and NEURODEVELOPMENT

Maternal inflammation and prenatal stress: Allostatic load during pregnancy may program offspring behaviour

Amanda Weiler, J. Keiko McCreary, Erin A. Falkenberg, Ashlee Matkin, Janet Poplawski, David M. Olson, Gerlinde A.S. Metz

Activation of the maternal immune system and psychological stress during pregnancy both can cause long-term health outcomes in offspring. We hypothesized that combined immune and psychological stressors represent two “hits” and synergistically increase allostatic load and behavioural impairments in offspring. Adult female rats were stressed on gestational days 12 to 18 and administered IL-1B daily from gestational day 17 until delivery. Offspring from different treatment groups (no stress/saline; no stress/IL-1B; stress/saline; stress/IL-1B) were tested in sensorimotor tasks. Prenatal stress and IL-1B treatments caused delays in sensorimotor development. Offspring born to stress/IL-1B mothers displayed the most severe. The observations support the two-hit hypothesis in the offspring and reflect cumulative allostatic load by combined maternal immune and psychological stress. The results provide insights into possible causes of neurodevelopmental disorders.

Enriched environment reduces allostatic load caused by ancestral stress

Teddi Reynolds, J. Keiko McCreary, Gerlinde A.S. Metz

Allostatic load (AL) is the cumulative burden of stress. AL is manifested in the physiological dysregulation across multiple systems that are involved in coping with stress. Here we developed an allostatic load index (AI) as a method to visualize the extent of stress-induced dysregulation across multiple systems. We used the AI to quantify the physiological burden caused by ancestral stress in rats, and we determined that enriched environment can offset the adverse health outcomes linked to AL. The use of an AI may represent a clinically valid method to evaluate biomarkers of chronic stress and to predict stress-associated disease risk.

Testing the “two-hit” hypothesis: Do stress and inflammation result in a synergistic effect on maternal health outcomes?

Janet Poplawski, J. Keiko McCreary, Erin A. Falkenberg, Ashlee Matkin, Amanda Weiler, David M. Olson, Gerlinde A.S. Metz

Exposure to stress during pregnancy can lead to negative maternal health outcomes. Studies have linked prenatal stress to increased risk of preterm birth, gestational diabetes, and maladaptive maternal behaviours. However, little is known about the effects of allostatic load (AL), or multiple hits by stress, on maternal health. In this study, pregnant rats were exposed to multiple stressors to determine whether gestational AL had synergistic effects on maternal health and pregnancy outcomes. We found that while AL induced certain physiological changes, others were associated with specific types of stress. This research provides insights into risk factors of adverse maternal health.

Like great-grandmother, like daughter: Mechanisms that promote stress resilience across generations
Hannah Scott, J. Keiko McCreary, Zachary T. Erickson, Gerlinde A.S. Metz

Transgenerational prenatal stress has been found to affect the behaviour and health of an individual. This project examined the effects of ancestral prenatal stress (APS) on adult hippocampal neurogenesis and functionality in the F4 generation. The protein brain-derived neurotrophic factor (BDNF) was chosen as an indicator of hippocampal plasticity, and was examined via Western blotting. Hippocampal integrity was evaluated by tests of learning and memory, including the water maze task. Although no effects of transgenerational stress on learning and memory were found, the results revealed that APS increased BDNF expression. These findings suggest transgenerationally programmed compensatory mechanisms to promote neural plasticity.

DISEASE MODELS, STRESS and ADDICTION

Prenatal exposure to a ‘double dose’ of valproic acid alters dendritic morphology in a rodent model of autism
Claire Niehaus, Sarah Raza, Allona Harker, Bryan Kolb, Robbin Gibb

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder ranging from mild to severe symptomology. With most research examining only high functioning ASD, the present study focused on the development of a viable rat model of low-functioning ASD. This was accomplished through an extension of the valproic acid (VPA) rodent model, whereby a single dose of VPA (800mg/kg) produces behavioural and neuroanatomical correlates similar to ASD in humans. To simulate low-functioning ASD, the dosage was increased from a single dose to a double dose of VPA (800mg/kg X 2). Neuroanatomical (Golgi) analyses of the affected offspring were conducted, including spine density, dendritic complexity, and dendritic ength of the Cg3 region of the brain.

Using experimental autoimmune encephalomyelitis as a mouse model of multiple sclerosis

Stella Babatunde, Rachael Chan, Vaibhav Singh, Brian Ficiur, V.Wee Yong, Gerlinde A.S. Metz

Multiple Sclerosis (MS) is an inflammatory demyelinating disease with high prevalence in Alberta. Studies have used experimental autoimmune encephalomyelitis (EAE) in mice to model the pathology of MS. The purpose of this study was to determine a dose-response relationship between EAE-inducing reagents and the severity of symptoms. All treated animals showed EAE symptoms, however, the severity and course of EAE did not correlate with the reagent concentration. In addition, some animals displayed a multiphasic course of EAE. This model may therefore provide a useful tool for studies of relapsing-remitting MS.

10.

Sit back, relax, and enjoy the trip? The impact of shipping stress on behavioural testing

Rachael Chan, Stella Babatunde, Brian Ficiur, Grace Forster, Gerlinde A.S. Metz

Stress impacts behavioural attributes and shipping stress is no exception. Our investigation sought to find if shipping stress has an adverse effect on behavioral test outcomes in mice, and if it affects response to an additional stressor. Male and female mice shipped from Charles-Rivers (CR) were compared to animals bred in-house (IH). The results suggest that shipping stress increased anxious behaviours compared to a non-stressed analogue. In post-stress tests, the CR mice displayed less motor movement and more anxiety than the IH mice. Thus, the source of animals represents a critical variable in neurobehavioural studies and stress research.

11.

Everyone loves road trips (except mice): The effects of shipment stress on motor function in adult mice

Grace Forster, Brian Ficiur, Stella Babatunde, Rachael Chan, Gerlinde A.S. Metz

Exposure to stress can lead to a number of adverse health outcomes. Uncontrollable stress may therefore change the results in biomedical studies. Here we proposed that shipment of animals from an external breeder induces stress that affects the results of neurobehavioural experiments. The motor abilities of adult mice shipped from a breeder were compared to those of animals bred in-house using footprint analysis. We found that an important parameter differed between the two groups of animals. These results indicate that shipment stress is a confounding variable and should be considered when evaluating the results of behavioural tests.

MEMORY & DECISION-MAKING

12. & 13.

Targeted memory reactivation quickens procedural skill learning

Cormac Southam, Jeremy Sloan, Masami Tatsuno

Targeted memory reactivation (TMR) is the process by which an unconditioned stimulus is associated with a memory and used to bias replay of that memory. TMR has been shown to increase the performance of explicit memory tasks; however, little work has been done on implicit memory. We tested if an auditory cue would increase the success rate of rats performing a reaching task. Although the success rate for both groups plateaued at the same level, the learning speed of the task was increased. We propose that TMR may be able to increase the rate of implicit memory learning.

14.
The effects of acute THC on reinforcement-driven decision-making

Sienna Randolph, Aaron Gruber

Dopamine release from midbrain structures is central to reinforcement learning as it provides a reward prediction error that enables us to make future choices leading to favourable outcomes, while avoiding those with adverse outcomes. Many drugs of abuse influence dopamine levels, altering our ability to learn from previous outcomes. Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis for example, acts to increase dopamine levels in the striatum. The effects of acute THC on reinforcement-driven response adaption in rats in a binary decision-making task are currently being studied in the Gruber lab. By understanding how THC alters flexible decision making, we can more fully understand the behavioural effects as they relate to addiction.

15.

Better by Surprise: The role of prediction in gambling addiction

Kyler Fisher, Catherine Laskowski, Hannah Wilson, David Euston

In a fixed-ratio (FR) schedule of reinforcement, reward is delivered for every fixed number of responses. In a random-ratio (RR) schedule of reinforcement, a reward is given after an average number of responses but the actual number of responses in a given trial varies unpredictably. The random-ratio schedule resembles slot-machine style gambling and as such might be a useful model of gambling. RR schedules differ from FR schedules primarily by reward delivery being unpredictable. We asked whether rats trained on RR would differ from rats trained on FR in operant chambers working for food pellet reward given that both groups were receiving equal quantities of reward for their responses across trials. Both groups are then to be tested on measures of addiction and we expected to find that the RR group will display more addictive behavior.

NEW METHODS AND TECHNOLOGIES

16.

Establishing a collection process for in vivo metabolomics

Zach Wanner, Tony Montina, Gerlinde A.S. Metz

Nuclear magnetic resonance (NMR) spectroscopy of in vivo microdialysis offers a unique potential to identify and quantify metabolites within the extracellular fluid of specific brain regions. Here we used microdialysis at different probe lengths and multiple buffer flow rates to collect samples for the analysis of extracelullar metabolomic profiles in mice. This technique may provide a promising new tool to identify real-time metabolic profiles linked to altered affective state and neurological disease in animal models.

17.

Adult-born neurons in the dentate gyrus lack AAV induced DREADD expression

Kate Chua, Justin Lee, Robert Surtherland, Robert McDonald

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are chemogenetic tools used to manipulate neural activity. DREADDs are often expressed using adeno-associated viruses (AAV) with cell-selective promoters. Until now AAVs 2 and 8 have not been used to characterize the expression of DREADDs in the rat hippocampus. Here, hippocampal injections of AAV 2 and 8 with neuron-specific promoters cause expression of DREADDs in the dentate gyrus (DG), but expression is not observed in new-born neurons in the DG subgranular zone. This may be useful in studies aiming to dissociate contributions of mature and newborn neurons in the DG.

18.

A CRISPR tool for genome editing: blocking the biosynthesis of histidine in bacterial cells

Bryant Young, David Cahana, Neal Melvin

Type II Clustered, Regularly, Interspaced Short Palindromic Repeats (CRISPR) nucleases for genome editing provides an easily modifiable nuclease via single-guide (sg)RNA that is flexible, efficient, low cost and sequence-specific. However, reprogramming of Cas9 in bacterial genomes induces cell death by chromosomal lesions. To circumvent this bias, Jian et al., (2013) developed a genome editing approach in bacteria using Cas9 as a marker-less selection catalyst in combination with Red Recombineering. This technique relies on reprogramming Cas9 to kill wild-type cells and using Red phage genes (gam, exo, bet) in order to introduce a site-specific mutations. Here I attempt to knockout the biosynthesis of histidine via the introduction of a stop codon (5’-TAA-3’) at positions 2,092,510 and 2,092,808 of the hisC gene – responsible for the synthesis of imidazole acetol phosphate aminotransferase – using CRISPR-Cas9 and Red Recombineering. This protein is a co-catalyst in the conversion of imidazolyacetolphosphate to L-histidinol phosphate, a key step in the biosynthesis of histidine. Histidine deficient bacteria are used to indirectly measure the mutagenic properties of chemical compounds. Initial round of editing recovered 0% of mutant colonies suggesting that optimization is in this approach is needed.

19.

Exploration of face detection with the use of artificial retinas

Marko Ilievski, Arren Glover, Chiara Bartolozzi, Matthew Tata

Humans are able to detect other human faces at an alarmingly fast rate, however this task has proven to be much more changing and time consuming for computers with the use of traditional cameras. This presentation will discuss the development within the new neuromorphic cameras and how these new cameras can be used to detect faces with a hopeful increase in speed.