Medicine and Health Sciences Commons^™

Impaired Object-Location Learning And Recognition Memory But Enhanced Sustained Attention In M2 Muscarinic Receptor-Deficient Mice, Carola Romberg, Susan Bartko, Jürgen Wess, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Muscarinic acetylcholine receptors are known to play key roles in mediating cognitive processes, and impaired muscarinic cholinergic neurotransmission is associated with normal ageing processes and Alzheimer’s disease. However, the specific contributions of the individual muscarinic receptor subtypes (M1–M5) to cognition are presently not well understood. Objectives: The aim of this study was to investigate the contribution of M2-type muscarinic receptor signalling to sustained attention, executive control and learning and memory. Methods: M2 receptor-deficient (M2−/−) mice were tested on a touchscreen-operated task battery testing visual discrimination, behavioural flexibility, object-location associative learning, attention and response control. Spontaneous …

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …

Genetic Manipulation Of Lactate Metabolism To Regulate Memory And Alzheimer's Disease Pathogenesis, Brainscan , Western University, Robert Cumming, Robert Bartha, Tim Scholl

Project Summaries

Our project will attempt to determine the relative importance of astrocyte or neuronal directed lactate generation on memory by modifying mouse models to either suppress or overexpress the lactate producing enzyme in either cell type. Using these newly created transgenic mouse models, we aim to understand the processes of production and utilization of lactate and its effect on memory and cognition in health and in AD across the lifespan. The outcome of our study may lead to entirely new clinical approaches to treating cognitive and neurodegenerative disorders via drugs which alter lactate metabolism.

The Role Of Astrocytes In Memory: Focus On Pattern Separation, Brainscan , Western University, Timothy Bussey, Vania Prado, Ceci Kramar, Marco Prado, Lisa Saksida

Project Summaries

It has recently been shown that astrocytes play a leading role in a particular aspect of memory known as 'pattern separation' - differentiating between similar experiences or episodes in memory (say, recalling where you parked your car today compared to where you parked it yesterday). Pattern separation is disrupted in a wide variety of diseases of the brain so it is of considerable interest to memory researchers.

We have already shown in a small pilot study that we can improve pattern separation with selective manipulation of astrocytes in a specific brain region. In this project, we will attempt to demonstrate …

Role Of Microglia Signaling In Brain Circuit Development And Cognition, Brainscan, Western University, Vania Prado, Marco Prado, Wataru Inoue

Project Summaries

We have generated two mouse models in which we can control the Gq and Gisignalling in microglia during specific periods of brain development so we can explore the mechanisms behind abnormal microglial function.

Using our mouse models, we can stimulate these signalling pathways during the critical period of postnatal brain development to understand whether they impact adult cognition by influencing normal synaptic pruning. Mouse models of autism show issues with social memory, attention, sociability and hyperactivity. We will therefore assess those behaviors in our mouse models to determine if any autism-like behaviours are present.

Integrating Behavioural, Imaging And Transcriptional Profiling To Discover The Impact Of Midlife Stress In Alzheimer's Disease, Brainscan , Western University, Tim Bussey, Flavio Beraldo, Chakravarty Maller, Rosemary Bagot, Sylvain Williams, Claudia Kleinman

Project Summaries

We will be integrating this cognitive assessment with imaging of brain structure and function to understand the mechanisms by which a risk factor, in this case modifiable life stress, influences Alzheimer's disease-related decline. The resultant data will be integrated and disseminated using a new open-access neuroinformatics platform developed at Western (MouseBytes.ca), which will become a unique resource for open science investigations and set the standard for sharing of behavioural data across the world.

Developing Optogenetics/Electrophysiology Applications For Studying Cognitive Impairment During Stress, Brainscan, Western University, Wataru Inoue, Brian Allman, Julio Martinez-Trujillo

Project Summaries

We will develop cutting-edge techniques to:

• precisely measure and artificially manipulate the activity of CRH neurons in the PFC, and
• measure small and local releases of CRH by these neurons.

The success of our project will open the door to understand the neural mechanisms for how stress impairs cognitive functions and how it may contribute to mental disorders.

Assessing Working Memory In Mild Cognitive Impairment With Serial Order Recall., Sheina Emrani, David J Libon, Melissa Lamar, Catherine C Price, Angela L Jefferson, Katherine A Gifford, Timothy J Hohman, Daniel A Nation, Lisa Delano-Wood, Amy Jak, Katherine J Bangen, Mark W Bondi, Adam M Brickman, Jennifer Manly, Rodney Swenson, Rhoda Au, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda)

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.

OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).

METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat …