Behavioural brain research
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Small (lacunar) infarcts frequently arise in frontal and midline thalamic regions in the absence of major stroke. Damage to these areas often leads to impairment of executive function likely as a result of interrupting connections of the prefrontal cortex. Thus, patients experience frontal-like symptoms such as impaired ability to shift ongoing behavior and attention. ⋯ Rats with mediodorsal thalamic lacunar damage did not exhibit a cognitive impairment relative to sham controls. The selective attention set shift impairment observed in this study is consistent with clinical data demonstrating selective executive disorders following stroke within specific sub-regions of frontal cortex. These data contribute to the development and validation of a preclinical animal model of executive dysfunction, that can be employed to identify potential therapies for ameliorating cognitive deficits following stroke.
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Behavioral sensitization to psychostimulants reflects neural adaptation, which might share a common mechanism with drug addiction. Outbred male rats show different locomotor sensitization responses to cocaine, and cocaine also produces varied addictive progress in humans. We investigated whether differences in the induction of sensitization would affect the long-term persistence of sensitized locomotor activity, and we sought to determine the molecular basis for the variability in sensitization. ⋯ We examined the level of phosphorylation of the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropioniate receptor (AMPAR) in the dorsal striatum and found that there were significant differences between the sensitized rats and the non-sensitized rats. pGluA1-Ser831 was increased in the SENS rats during the induction of locomotor sensitization, and pGluA1-Ser845 was increased in the SENS-C rats during the expression of locomotor sensitization. These phosphorylation changes were observed in the dorsomedial striatum (DMS) of adult rats but not in the dorsolateral striatum (DLS) of adults. Our findings suggest that differential phosphorylation of AMPAR might be an important mechanism that contributes to the development of locomotor sensitization to cocaine in adult rats.
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Obsessive-compulsive disorder (OCD) is characterized by recurrent thoughts and repetitive motor actions. Hyposerotonergic signalling in the cortico-striatal circuitry is believed to be central to the pathology of OCD, while many patients only respond to chronic treatment with high dose selective serotonin (5HT) reuptake inhibitors (SSRIs). ⋯ Furthermore, HS deer mice present with a significant decrease in striatal SERT density compared to non-stereotypical (NS) controls. Building on previous validation studies, we conclude that deer mouse stereotypy is a valid naturalistic animal model of OCD with robust face, construct and predictive validity.
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We characterize the effects of sleep deprivation on sleep-wake behavior, neurogenesis and stress in adult zebrafish, and describe light-induced changes in gene expression. Sleep deprivation was performed using two stimuli: mild electroshock and light. Comparisons were made between five groups of fish: naïve; electroshock sleep-deprived and yoked-control; fish exposed to constant light (increasing wakefulness); and fish exposed to constant darkness (increasing sleep). ⋯ Finally, modulation of gene expression by light and dark was observed. Genes upregulated during the dark period are broadly related to growth, morphogenesis, energy balance, and lipid synthesis. Genes upregulated during light are broadly related to synaptic plasticity and cell proliferation.
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The stop-signal paradigm is increasingly being used as a probe of response inhibition in basic and clinical neuroimaging research. The critical feature of this task is that a cued response is countermanded by a secondary 'stop-signal' stimulus offset from the first by a 'stop-signal delay'. Here we explored the role of task difficulty in the stop-signal task with the hypothesis that what is critical for successful inhibition is the time available for stopping, that we define as the difference between stop-signal onset and the expected response time (approximated by reaction time from previous trial). ⋯ We found that the time available for stopping distinguished successful from unsuccessful inhibition trials, was independent of stop-signal delay, and affected successful inhibition depending upon individual SSRT. We also found that right IFG and adjacent anterior insula were more strongly activated during more difficult stopping. These findings may have critical implications for stop-signal studies that compare different patient or other groups using fixed stop-signal delays.