ABSTRACT
The Locus Coeruleus (LC) is in the brainstem and supplies key brain structures with noradrenaline, including the forebrain and hippocampus. The LC impacts specific behaviors such as anxiety, fear, and motivation, as well as physiological phenomena that impact brain functions in general, including sleep, blood flow regulation, and capillary permeability. Nevertheless, the short- and long-term consequences of LC dysfunction remain unclear. The LC is among the brain structures first affected in patients suffering from neurodegenerative diseases such as Parkinson's disease and Alzheimer's Disease, hinting that LC dysfunction may play a central role in disease development and progression. Animal models with modified or disrupted LC function are essential to further our understanding of LC function in the normal brain, the consequences of LC dysfunction, and its putative roles in disease development. For this, well-characterized animal models of LC dysfunction are needed. Here, we establish the optimal dose of selective neurotoxin N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP-4) for LC ablation. Using histology and stereology, we compare LC volume and neuron number in LC ablated (LCA) mice and controls to assess the efficacy of LC ablation with different numbers of DSP-4 injections. All LCA groups show a consistent decrease in LC cell count and LC volume. We then proceed to characterize the behavior of LCA mice using a light-dark box test, Barnes maze test, and non-invasive sleep-wakefulness monitoring. Behaviorally, LCA mice differ subtly from control mice, with LCA mice generally being more curious and less anxious compared to controls consistent with known LC function and projections. We note an interesting contrast in that control mice have varying LC size and neuron count but consistent behavior whereas LCA mice (as expected) have consistently sized LC but erratic behavior. Our study provides a thorough characterization of an LC ablation model, firmly consolidating it as a valid model system for the study of LC dysfunction.
ABSTRACT
The defensive activation theory (DAT) was recently proposed to explain the biological function of dreaming. Briefly, DAT states that dreams are primarily visual to prevent plastic take-over of an otherwise inactive visual cortex during sleep. Evidence to support the DAT revolve around the interplay between dream activity (REM%) and cortical plasticity found in evolutionary history, primate studies, and coinciding decline in human cortical plasticity and REM% with age. As the DAT may prove difficult to test experimentally, we investigate whether further support for the DAT can be found in the literature. Plasticity and REM sleep are closely linked to functions of the Locus Coeruleus (LC). We therefore review existing knowledge about the LC covering LC stability with age, and the role of the LC in the plasticity of the visual cortex. Recent studies show the LC to be more stable than previously believed and therefore, the LC likely supports the REM% and plasticity in the same manner throughout life. Based on this finding, we review the effect of aging on REM% and visual cortex plasticity. Here, we find that recent, weighty studies are not in complete agreement with the data originally provided as support for DAT. Results from these studies, however, are not in themselves irreconcilable with the DAT. Our findings therefore do not disprove the DAT. Importantly, we show that the LC is involved in all mechanisms central to the DAT. The LC may therefore provide an experimental window to further explore and test the DAT.