Development and characterization of novel transgenic techniques for the study of neuronal circuitry

Modern neuroscience relies heavily on sophisticated tools that allow us to visualize and manipulate cells with precise spatial and temporal control. Transgenic mouse models, for example, can be used to manipulate cellular activity in order to draw conclusions about the molecular events responsible for the development, maintenance and refinement of healthy and/or diseased neuronal circuits. Although it is fairly well established that circuits respond to activity-dependent competition between neurons, we have yet to understand either the mechanisms underlying these events or the higher-order plasticity that synchronizes entire circuits. In this thesis we aimed to develop and characterize transgenic mouse models that can be used to directly address these outstanding biological questions in different ways. We present SLICK-H, a Cre-expressing mouse line that can achieve drug-inducible, widespread, neuron-specific manipulations in vivo. This model is a clear improvement over existing models because of its particularly strong, widespread, and even distribution pattern that can be tightly controlled in the absence of drug induction. We also present SLICK-V::Ptox, a mouse line that, through expression of the tetanus toxin light chain, allows long-term inhibition of neurotransmission in a small subset (<1%) of fluorescently labeled pyramidal cells. This model, which can be used to study how a silenced cell performs in a wildtype environment, greatly facilitates the in vivo study of activity-dependent competition in the mammalian brain. As an initial application we used this model to show that tetanus toxin-expressing CA1 neurons experience a 15% - 19% decrease in apical dendritic spine density. Finally, we also describe the attempt to create additional Cre-driven mouse lines that would allow conditional alteration of neuronal activity either by hyperpolarization or inhibition of neurotransmission. Overall, the models characterized in this thesis expand upon the wealth of tools available that aim to dissect neuronal circuitry by genetically manipulating neurons in vivo.

The demise of the Beothuk as a past still present

This article aims to investigate contemporary cultural representations of the Beothuk Indians in art, literature and museum displays in Newfoundland, Canada, focussing on ways these reimagine the past for the present, offering perspectives on contested histories, such as the circumstances leading to the demise of the Beothuk. Wiped out through the impact of colonialism, the Beothuk are the ‘absent other’ who continue to be remembered and made present through the creative arts, largely at the expense of other indigenous groups on the island. Rather than focussing on the ‘non-absent past, according to Polish scholar Ewa Domańska, ‘instead we turn to a past that is somehow still present, that will not go away or, rather, that of which we cannot rid ourselves’ (2006, 346). Depictions of the last Beothuk are part of a cultural remembering where guilt and reconciliation are played out through media of the imagination