I am interested in the relationship between epilepsy, behavioural disruption and its mechanistic underpinnings as well as methods of reversing seizure-induced alterations in behaviour and brain.
We use a model of cerebral ischemia (stroke) to determine effective treatments to facilitate recovery. In collaboration with Northstar Neuroscience we have determined that cortical surface electrical stimulation facilitates the recovery process. We continue to investigate the efficacy and safety of electrical stimulation as well as whether adjunctive therapies can additionally improve recovery. Figure of a coronal section from rat brain showing a stroke in the neocortical region of the left hemisphere.
The Cellular/Synaptic Basis of Learning and Memory Studies
A long-standing and central question in Psychology and Behavioural Neuroscience is, “How does experience change the brain”? Many of us working on this vexing question believe that an alteration in the connections (synapses) between neurons allows a restructuring of neural circuits (engrams) to encode memories. Thus, the theoretical framework in which I work is aptly called the synaptic plasticity and memory theory. This theory also holds that a particular memory is distributed within the brain regions responsible for that behaviour and it is located among other previously formed memories. Many of us who study the physical instantiation of memory have traditionally employed experimental phenomena that alter synaptic connectivity in a controlled manner and that may utilize identical, or at least similar, mechanisms to memory formation. Thus, one of my main lines of research has used three such phenomena: kindling, long-term potentiation (LTP) and long-term depression (LTD). I used kindling when interested in saturating the plastic capacity of a neural system because kindling is a robust phenomenon that causes widespread and exaggerated changes in the functional organization of the brain. I use LTP/LTD because LTP is one of the most widely studied models of the synaptic enhancements that are thought to underlie memory formation whereas LTD is in many ways the reverse of LTP whereby synapses can be weakened in a controlled manner. My laboratory has also directly studied the effects of different forms of behavioural experience on brain function and anatomy.
My students, collaborators and I have published many experiments examining synaptic plasticity and movement representations (motor maps) within the rat forelimb area of sensorimotor neocortex. This area shows synaptic potentiation and depression phenomena that are correlated with anatomical changes. Most importantly, learning skilled behaviours of the forelimb are dependent on the integrity of this area of motor cortex and result in functional and anatomical changes. Thus, we have an easily accessible neuroanatomical region within which to focus our exploration of the relationship between brain and behaviour, as well as the reciprocal relationship between behaviour and brain.
Most of my published work over the last 5 year period examined the relationship between brain and behaviour by utilizing artificial stimulation models and behavioural training. That work was built on our novel observation that the neocortex of awake, behaving animals could support potentiation phenomena. Furthermore we found that the “rules” of neocortical LTP induction and decay differed from those in the hippocampus. This was a particularly important finding because theoreticians had postulated multiple, independent learning systems with properties that correspond with our observations.
Stereotypic behaviours are defined as the excessive, invariant and repeated production of one type of motor act, in which no obvious goal or function is apparent. Stereotypic behaviours are commonly found in humans and across a wide variety of domestic and non-domestic, captive animal species. A large proportion (55-100%) of captive polar bears have been reported to exhibit stereotypic behaviours, most often expressed as pacing. In fact, polar bear pacing is so common that in the Dutch language there is the verb "ijsberen" (to polar-bear) which is translated as walking up and down restlessly. Afflicted individuals may spend most of their waking time performing stereotypic behaviours and for this reason, they are thought to constitute a major animal health issue.
The causes of stereotypic behaviours are most likely heterogeneous in origin. Factors such as stress, learned responses, brain damage, confined spaces and an impoverished environment have all been implicated. It is interesting to note that descriptions of stereotypic behaviours in captive and domestic animals show numerous commonalities with the descriptions of human obsessive compulsive disorder (OCD). In fact, there is good evidence of a common link between animal stereotypic behaviours and human OCD; the serotonergic system. Successful pharmacological treatment of human and animal stereotypic behaviours has involved altering serotonin (5-hydroxytryptophan (5-HT)) neurotransmission.
Fluoxetine, more commonly known as Prozac, is a widely studied and prescribed second generation anti-depressant compound. Fluoxetine and its major metabolite, norfluoxetine, both function as potent and selective 5-HT reuptake inhibitors (SSRI). While fluoxetine is not more efficacious than established tricyclic compounds, its high degree of selectivity reduces the side effects associated with the tricyclics, and has made fluoxetine the drug of choice when treating human OCD. Fluoxetine has been used successfully for the treatment of human stereotypic disorders such as OCD, Tourette's syndrome, anorexia nervosa, bulimia nervosa, and trichotillomania as well as stereotypic paw licking in domestic dogs. We assessed the effects of fluoxetine treatment on both chronic stereotypic pacing and typical behaviours of one captive polar bear at the Calgary Zoo.
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