Supporting Graduate Student Research

Graduate Student Publication of the Month

Nicole M. LauzonDepartment of Anatomy & Cell Biology 

Manuscript Title: Supra-normal stimulation of dopamine D­1 receptors in the prelimbic cortex blocks behavioral expression of both aversive and rewarding associative memories through a cyclic-AMP-dependent signaling pathwayCitation: Neuropharmacology. 2012 Nov 16 [Epub ahead of print]
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Student Biography:
Nicole Lauzon completed her undergraduate degree at Western University in 2007 and is now a PhD candidate in the department of Anatomy & Cell Biology. During her undergraduate career she specialized in Pharmacology & Toxicology, Microbiology & Immunology as well as completing an additional Major in Psychology.  Now in her PhD she focuses on the neurobiology of psychological disorders such as schizophrenia, PTSD, drug addiction and ADHD. Her main focus it to elucidate the mechanisms underlying some of the cognitive deficits in these disorders, in hopes to contribute to a better understanding and possibly better treatment for the people affected by these debilitating disorders. Throughout her graduate career Nicole has received support from OGSST and is currently funded by the NSERC – Alexander Graham Bell Canada Graduate Scholarship.

Manuscript Synopsis and Significance:
Our manuscript describes some novel and exciting new findings from our lab wherein we reveal a unique role for specific, dopamine “D1” receptor transmission within the prelimbic cortical division of the medial prefrontal cortex, in controlling the spontaneous recall of associative memories. Specifically, we report that direct stimulation of D1 receptors within the rat prelimbic cortex can completely block the recall of both ‘aversive’ or ‘rewarding’ associative memories, as measured in either a fear conditioning procedure, or in a classic morphine conditioned ‘place preference’ behavioural assay. Interestingly, we found that while D1 receptor stimulation was able to completely block spontaneous memory recall, the original memory traces were left intact, as memory recall was restored in the absence of D1 receptor stimulation or in the presence of a previously paired cue.

Our findings have important implications for understanding disorders such as post-traumatic stress disorder and addiction, both of which are characterized by the obtrusive recall of memories linked to either aversive experiences, or drug-related reinforcement memories. In addition, our effect was dependent specifically upon D1 receptor stimulation, with no effects on memory recall found with stimulation of D2-like receptor substrates in the same cortical region. Finally, we report a common molecular mechanism underlying these effects, as the D1 receptor-mediated block in associative
memory recall was rescued by simultaneous inhibition of cyclic-AMP signaling.

Press Coverage for this Publication

CTV London Evening News, 6 pm, December 6th 2012


Kevin Skoblenick--MD/PhD (Department of Anatomy & Cell Biology)


Publication Title: NMDA antagonist ketamine reduces task selectivity in macaque dorsolateral prefrontal neurons and impairs performance of randomly interleaved prosaccades and antisaccades.

J Neurosci. 2012 Aug 29;32(35):12018-27. doi: 10.1523/JNEUROSCI.1510-12.2012.

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Student Biography:

 Kevin Skoblenick received his Honours B.Sc. in the Biology/Psychology program at McMaster University. He continued on to complete his M.Sc. in the department of Medical Sciences at McMaster University during which he was funded with an NSERC post-graduate scholarship. From this work at McMaster University he produced 13 publications in a variety of peer-reviewed journals. He joined Western University in 2009 as an MD/Ph.D. student and is completing his Ph.D. training in the department of Anatomy and Cell Biology under the supervision of Dr. Stefan Everling. His research is supported by a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award. Kevin’s initial studies in antipsychotic pharmacology ignited his interest in psychiatric research and with this unique background he was able to open a new branch of neuropharmacological research in Dr. Everling’s laboratory.

Schizophrenia is often considered one of the most complex mental disorders.  Unfortunately, we understand very little about the neural processes responsible for the variety of symptoms accompanying this disease. A single, low dose injection of the anaesthetic ketamine can induce a short-lived behavioural profile that resembles schizophrenia in both humans and non-human primates. In order to test for cognitive deficits following ketamine administration we used a task in which the subject must suppress the instinctual act of looking towards a novel visual stimulus and instead look towards a blank area of the screen opposite the stimulus. Our study shows that ketamine increased error rates and reaction times in non-human primates just like it does in humans and these changes are similar to the deficits observed in patients with schizophrenia. We also recorded from the prefrontal cortex while the subjects were performing the task as this region has been critically linked to cognitive function. Prior to ketamine administration, neurons in this area were task-selective and displayed higher activity for specific task rules. Following ketamine administration, however, this specificity was lost. While most neurons displayed a net increase in firing rate, this increased activity was non-specific leading to ‘noisy’ prefrontal cortex activity. In summary, this study shows how the task-selective neurons in the prefrontal cortex may play a critical role in the cognitive control over behaviour and lays the groundwork for describing a neural basis of the ketamine model of schizophrenia.


Ian Lobb--Microbiology and Immunology


Publication Title: Supplemental hydrogen sulphide protects transplant kidney function and prolongs recipient survival after prolonged cold ischaemia–reperfusion injury by mitigating renal graft apoptosis and inflammation.

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What's known on the subject?  What does the study add?

Hydrogen sulphide (H2S) has recently been classified as a member of the family of small gaseous molecules called gasotransmitters and has been found to have many important physiological functions. Several recent studies have elucidated the protective effects of H2S in many models of tissue ischaemia–reperfusion injury (IRI), including hepatic, myocardial, pulmonary, cerebral and renal IRI. It has previously been shown that H2S has a number of properties that may contribute to its protection against IRI, including vasodilatory, anti-apoptotic, anti-inflammatory and anti-oxidant effects, although the specific actions appear to vary between tissues.

The few studies investigating the effects of H2S against renal IRI have only involved clamping of the renal pedicle to induce warm IRI. This study investigated the protective effects of H2S in the context of renal transplantation (RTx), which generally involves a more severe period of prolonged cold IRI. A previous study investigated the actions of H2S in RTx, but it was performed ex vivo and did not involve actual transplantation of donor kidneys. To our knowledge, this is the first study using a clinically relevant model of RTx to show that treatment of donor kidneys with H2S during preservation is protective against prolonged cold IRI. These findings suggest that H2S has potential utility in improving clinical organ preservation techniques and increasing the overall success of organ transplantation.


Our results provide the first evidence that supplemental H2S can mitigate renal graft IRI incurred during transplantation and prolonged cold storage, improving early graft function and recipient survival in a clinically applicable model of RTx.

Jessica Esseltine--Physiology & Pharmacology

Publication title: Rab8 modulates metabotropic glutamate receptor subtype 1 intracellular trafficking and signaling in a protein kinase C-dependent manner.

Esseltine JL, Ribeiro FM, Ferguson SS.
J Neurosci. 2012 Nov 21;32(47):16933-42. doi: 10.1523/JNEUROSCI.0625-12.2012.

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Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors (GPCRs) that are activated by glutamate, the primary excitatory neurotransmitter in the CNS. Alterations in glutamate receptor signaling are implicated in neuropathologies such as Alzheimer's disease, ischemia, and Huntington's disease among others. Group 1 mGluRs (mGluR1 and mGluR5) are primarily coupled to Gα(q/11) leading to the activation of phospholipase C and the formation of diacylglycerol and inositol 1,4,5-trisphosphate, which results in the release of intracellular calcium stores and protein kinase C (PKC) activation. Desensitization, endocytosis, and recycling are major mechanisms of GPCR regulation, and the intracellular trafficking of GPCRs is linked to the Rab family of small G proteins. Rab8 is a small GTPase that is specifically involved in the regulation of secretory/recycling vesicles, modulation of the actin cytoskeleton, and cell polarity. Rab8 has been shown to regulate the synaptic delivery of AMPA receptors during long-term potentiation and during constitutive receptor recycling. We show here that Rab8 interacts with the C-terminal tail of mGluR1a in an agonist-dependent manner and plays a role in regulating of mGluR1a signaling and intracellular trafficking in human embryonic kidney 293 cells. Specifically, Rab8 expression attenuates mGluR1a-mediated inositol phosphate formation and calcium release from mouse neurons in a PKC-dependent manner, while increasing cell surface mGluR1a expression via decreased receptor endocytosis. These experiments provide us with an understanding of the role Rabs play in coordinated regulation of mGluR1a and how this impacts mGluR1a signaling.

In Jessica's words:
"We found that the small G protein Rab8 associates with the G protein-coupled receptor (GPCR) mGluR1a. Through this association, Rab8 inhibits receptor internalization and attenuates signaling in a PKC-dependent manner, resulting in increased overall cell surface mGluR1 expression. Multiple Rabs have been shown to be involved in both endocytic and exocytic events. However, this is the first time a Rab has been shown to inhibit internalization. Therefore, we present a novel role for Rab8 in attenuating mGluR1a internalization and signalling, which opens a new and exciting avenue of research into the role of Rabs in GPCR regulation. Future studies will focus on the role of Rab8 in mGluR signaling during Huntingtin's disease. These proteins have each been implicated in the disease, but the role they play together is not yet defined.
I completed my B.Sc. honors genetics in 2006 from the department of Biology, UWO. I will be leaving in January for a post doc studying A-kinase anchoring proteins in the laboratory of Dr. John D. Scott at the University of Washington, Seattle".


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