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Although neonicotinoids are among the major classes of pesticides that affect mammalian nervous systems, little is known about sex differences in their effects. This study aimed to examine whether the neurobehavioral effects of a neonicotinoid, clothianidin (CLO), differed between sexes. Male and female C57BL/6N mice were orally administered CLO (5 or 50 mg/kg) at or below the chronic no-observed-adverse-effect-level (NOAEL) and sub- jected to behavioral tests of emotional and learning functions. Changes in neuroactivity in several brain regions and the concentrations of CLO and its metabolites in blood and urine were measured. Acute CLO exposure caused sex-related behavioral effects; decreases in locomotor activities and elevation of anxiety-like behaviors were more apparent in males than in females. In addition, male-specific impairment of short- and long-term learning memory by CLO exposure was observed in both the novel recognition test and the Barnes maze test. Male- dominant increases in the number of c-fos positive cells were observed in the paraventricular thalamic nu- cleus in the thalamus and in the dentate gyrus in the hippocampus, which are related to the stress response and learning function, respectively. The concentrations of CLO and most metabolites in blood and urine were higher in males. These results support the notion that male mice are more vulnerable than females to the neuro- behavioral effects of CLO and provide novel insights into the risk assessment of neonicotinoids in mammalian neuronal function.

Synaptic plasticity (long-term potentiation, LTP and long-term depression, LTD) plays an important role in processes of learning and memory formation. In order to provide a link between these neurophysiological and cognitive processes the following experiments were performed using behavioral, electrophysiological, and pharmacological in vivo methods in order to describe synaptic plasticity in the adult rat visual system after learning a simple visual discrimination task. Initially, a novel method is described providing a simple and noninvasive means to restrict visual input. Using a harness and face-mask for monocular occlusion, rats were trained in a monocular visual discrimination task using a Y-shaped water maze. Following learning, assessment of synaptic plasticity in the thalamocortical visual pathway found both general (changes in short-term plasticity in both cerebral hemispheres) and localized changes (greater LTP levels in the hemisphere contralateral to the open eye). The enhanced LTP in the primary visual cortex (V1) was blocked by an NR2B antagonist, suggesting that training resulted in changes in NMDA receptor expression or functioning. Next, the effectiveness of LTD stimulation protocols to elicit synaptic depression under in vivo conditions were assessed. Of several single-pulse induction protocols tested, only strong low frequency burst stimulation (SLFS) produced significant, but transient (~20 min) depression in V1 (not affected by blockade of NMDA or metabotrobic glutamate receptors). These data highlight the resistance of the thalamocortical visual system to undergo synaptic depression in vivo. To examine whether learning alters LTD induction, SLFS was delivered to the thalamocortical visual pathway or the V1-perirhinal cortex pathway following visual discrimination. Neither pathway exhibited changes in LTD following training, suggesting that the learning-induced LTP facilitation reflects an expansion of the synaptic modification range. Finally, Thesis (Ph.D, Psychology) -- Queen's University, 2015-03-19 14:57:24.553