Browsing by Subject "Rat"
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Item Open Access Neuronal Correlates of Reward Contingency in the Rat Thalamocortical System(2009) Pantoja, Janaina HernandezPerception arises from sensory inputs detected by peripheral organs and processed in the brain by complex neuronal circuits required for the integration of external information with internal states such as expectation and attention. Stimulus discrimination requires activation of primary sensory areas in the brain, but expectation is traditionally associated with the activation of higher-order brain areas. Sensory information obtained by tactile organs is represented along the primary areas that comprise the trigeminal thalamocortical pathway. In anesthetized animals, neuronal activity in the somatosensory system has been extensively described over the past century. However, it is still unclear how the different thalamocortical structures contribute to active tactile discrimination and represent relevant features of the stimulus. It is also unknown whether expectation modulates tactile representations in these regions. In this dissertation, I investigated neuronal ensemble activity recorded from freely behaving rats performing a whisker-based tactile discrimination t-+ask. Multielectrode arrays were chronically implanted to record simultaneously from the main stages of the trigeminal thalamocortical pathways involved in whisking: the primary somatosensory cortex (S1), the ventral posterior medial nucleus of the thalamus (VPM), the posterior medial complex (POm) and the zona incerta (ZI). In Chapter 1 I describe the behavior of rats performing the tactile discrimination task, which requires animals to associate two different tactile stimuli with two corresponding choices of spatial trajectory in order for reward to be delivered. I found that both cortical and thalamic neurons are dynamically engaged during execution of the task. The data reveal a very complex mosaic of responses comprising single or multiple periods of inhibition and excitation. Thalamocortical activity was modulated during whisker stimulation as well as after stimulus removal, up until reward delivery. To investigate whether reward expectation plays a role in tactile processing at early processing stages, I also recorded neuronal activity from rats performing a freely-rewarded version of the tactile discrimination task. Comparing data from regularly-rewarded and freely-rewarded sessions, I show in chapter 2 that the activity of single neurons in the primary somatosensory thalamocortical loop is strongly modulated by reward expectation. Stimulus-related information coded by primary thalamocortical neurons is high when a correct association between stimulus and response is crucial for reward, but decreases significantly when the association is irrelevant. These results indicate that tactile processing in primary somatosensory areas of the thalamus and cerebral cortex is directly affected by reward expectation.
Item Open Access Paternal nicotine exposure in rats produces long-lasting neurobehavioral effects in the offspring.(Neurotoxicology and teratology, 2019-05-16) Hawkey, Andrew B; White, Hannah; Pippen, Erica; Greengrove, Eva; Rezvani, Amir H; Murphy, Susan K; Levin, Edward DStudies of intergenerational effects of parental chemical exposure have principally focused on maternal exposure, particularly for studies of adverse neurobehavioral consequences on the offspring. Maternal nicotine exposure has long been known to cause adverse neurobehavioral effects on the offspring. However, paternal toxicant exposure has also been found to cause neurobehavioral toxicity in their offspring. Recent work suggests that paternal nicotine exposure can have epigenetic effects, although it remains unclear whether such changes lead to neurobehavioral effects. In the current study, we investigated the effects of paternal nicotine exposure on neurobehavioral development of their offspring. Male Sprague-Dawley rats were exposed to 0 or 2 mg/kg/day nicotine (sc) for 56 consecutive days with two consecutive 2ML4 osmotic minipumps. Following treatment, these males were mated with drug-naïve female rats. Offspring of both sexes were tested in a behavioral battery to assess locomotion, emotional function and cognition. Paternal nicotine exposure did not impact offspring viability, health or growth. However, behavioral function of the offspring was significantly altered by paternal nicotine exposure. Male offspring with paternal nicotine exposure exhibited locomotor hyperactivity in the Figure-8 apparatus when tested during adolescence. When retested in adulthood and regardless of sex, offspring of the nicotine exposed father showed significantly reduced habituation of locomotor activity over the course of the session. Compared to controls, female offspring of nicotine-exposed fathers showed significantly reduced response latency in the radial arm maze test. In addition to locomotor hyperactivity, the offspring of nicotine-exposed fathers also showed significantly diminished habituation in the novel object recognition test. These results indicate that chronic paternal nicotine exposure can impact the behavior of offspring, producing locomotor hyperactivity and impaired habituation.Item Open Access Quantitative mapping of trimethyltin injury in the rat brain using magnetic resonance histology.(Neurotoxicology, 2014-05) Johnson, G Allan; Calabrese, Evan; Little, Peter B; Hedlund, Laurence; Qi, Yi; Badea, AlexandraThe growing exposure to chemicals in our environment and the increasing concern over their impact on health have elevated the need for new methods for surveying the detrimental effects of these compounds. Today's gold standard for assessing the effects of toxicants on the brain is based on hematoxylin and eosin (H&E)-stained histology, sometimes accompanied by special stains or immunohistochemistry for neural processes and myelin. This approach is time-consuming and is usually limited to a fraction of the total brain volume. We demonstrate that magnetic resonance histology (MRH) can be used for quantitatively assessing the effects of central nervous system toxicants in rat models. We show that subtle and sparse changes to brain structure can be detected using magnetic resonance histology, and correspond to some of the locations in which lesions are found by traditional pathological examination. We report for the first time diffusion tensor image-based detection of changes in white matter regions, including fimbria and corpus callosum, in the brains of rats exposed to 8 mg/kg and 12 mg/kg trimethyltin. Besides detecting brain-wide changes, magnetic resonance histology provides a quantitative assessment of dose-dependent effects. These effects can be found in different magnetic resonance contrast mechanisms, providing multivariate biomarkers for the same spatial location. In this study, deformation-based morphometry detected areas where previous studies have detected cell loss, while voxel-wise analyses of diffusion tensor parameters revealed microstructural changes due to such things as cellular swelling, apoptosis, and inflammation. Magnetic resonance histology brings a valuable addition to pathology with the ability to generate brain-wide quantitative parametric maps for markers of toxic insults in the rodent brain.