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https://doi.org/10.21307/ane-2019-027

We examine the maintenance and behavioural expression of long-term memories acquired in the absence of the hippocampus. The hypothesis that the hippocampus is necessary to form stable and detailed long-term memories is tested. We find rats with extensive hippocampal damage made before learning exhibit normal maintenance and behavioural expression of contextual fear memory, object discrimination, and context discrimination. The discovery that non-hippocampal networks can encode, maintain, and retrieve memories, widely-thought to be dependent on the hippocampus and its consolidation processes adds to a growing body of literature which draws into question most views of the hippocampus and memory consolidation. Our findings suggest: 1) hippocampal-dependent systems-level consolidation is not required for stable long-term memory in the rat; 2) non-hippocampal networks possess sufficient representational complexity to support normal discriminative memory-guided behaviours; 3) the broad distinction between hippocampal and non-hippocampal memories requires re-evaluation through rigorous experimentation, rather than adherence to modal views.

Sporadic Alzheimer’s disease (AD) is the most prevalent form of age-related dementia. As such, great effort has been put forth to investigate the etiology, progression, and underlying mechanisms of the disease. Countless studies have been conducted, however, the details of this disease remain largely unknown. Rodent models provide opportunities to investigate certain aspects of AD that cannot be studied in humans. These animal models vary from study to study and have provided some insight, but no real advancements in the prevention or treatment of the disease. In this Hypothesis and Theory paper, we discuss what we perceive as barriers to impactful discovery in rodent AD research and we offer potential solutions for moving forward. Although no single model of AD is capable of providing the solution to the growing epidemic of the disease, we encourage a comprehensive approach that acknowledges the complex etiology of AD with the goal of enhancing the bidirectional translatability from bench to bedside and vice versa.

The present thesis examines the effects of transcranial direct current stimulation and forelimb rehabilitation on motor recovery after stroke in rats. Post-stroke motor outcomes were quantified using an innovative battery of behavioural tests and high resolution, in vivo electrophysiology was employed to examine coherence of neural activity between hemispheres. It was shown that rats that received brain stimulation concurrently with forelimb rehabilitation displayed functional recovery, whereas rats that received rehabilitation alone partially regained motor function, but the improvements were not due to restitution of original movement patterns. Results from electrophysiological recordings showed that rats that received brain stimulation and rehabilitation regained pre-stroke levels of interhemispheric coherence, but rats that received rehabilitation alone did not. The present thesis suggests that transcranial direct current stimulation may be a viable adjunct therapy to increase the efficacy of physical rehabilitation with regard to post-stroke motor outcomes. Interhemishperic coherence between homotopic neuronal populations may represent a biomarker of genuine motor recovery after stroke.