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- ItemHypothalamic Hyperphagia(Produced at the University of Lethbridge, 1978) Whishaw, Ian Q.; Kolb, BryanA film by Ian Q. Whishaw and Bryan Kolb based on research by Thomas Wishart, The University of Saskatchewan. Photography by Bryan Kolb and Landy L. Esau. Produced at the University of Lethbridge.
- ItemApraxia in Hamsters(Produced at the University of Lethbridge, 1979) Kolb, Bryan; Whishaw, Ian Q.A film by Bryan Kolb and Ian Q. Whishaw and based on research by Bryan Kolb, Jim Shipley and Ian Q. Whishaw. Photography by L. L. Esau. Produced at the University of Lethbridge.
- ItemExperimental stimulation as a treatment for early brain damage(Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2001, 2001) Gibb, Robbin L.; University of Lethbridge. Faculty of Arts and Science; Kolb, BryanThe current work explores the therapeutic potential of experiential treatments for enhancing functional recovery and anatomical change after early brain damage. Normal rats and rats with perinatal cortical lesions (P2 or P7) were exposed to one of the following treatments: complex housing as juveniles, complex housing as adults, prenatal tactile stimulation, postnatal tactile stimulation, or postnatal handling (removal from the nest with no additional stimulaion). Behavior was assessed in adulthood the Morris water task and the Whishaw reaching task. There were sex differences in the details of the effect of experience on both behavioral recovery and brain morphology. For both sexes treatments initiated prior to or immediately after brain injury were most effective in improving functional outcome. This was correlated with changes in dendritic arborization and Acetylcholinesterase staining. The results suggest that behavioral treatments can be used to stimulate functional recovery after early brain injury.
- ItemPerinatal experience alters brain development and functional recovery after cerebral injury in rats(Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2004, 2004) Gibb, Robbin L.; University of Lethbridge. Faculty of Arts and Science; Kolb, BryanBrain damage in the first week of life is behaviorally and anatomically devastating for a rat. I investigated the use of pre- and/or postnatal experience as interventions that might improve the outcomes in rats with postnatal day 4 (P4) frontal cortex lesions. Prenatal maternal tactile stimulation or maternal complex housing facilitated recovery in P4 lesion animals and produced changes in brain organization. Post-lesion tactile stimulation also was found to be beneficial possibly via experience dependent changes in FGF-2 expression. Levels of FGF-2 were increased in both skin and brain after tactile stimulation and correlated with behavioral and anatomical changes. Direct post-lesion administration of FGF-2 had similar effects. These results are the first demonstration that prenatal experience can be prophylactic for postnatal brain injury and that behavioral experience can act on brain organization via enhanced trophic factor expression originating in skin.
- ItemMusic attenuates excessive visual guidance of skilled reaching in advanced but not mild Parkinson's disease(Public Library of Science, 2009) Sacrey, Lori-Ann Rosalind; Clark, Callie Anne Marie; Whishaw, Ian Q.Parkinson’s disease (PD) results in movement and sensory impairments that can be reduced by familiar music. At present, it is unclear whether the beneficial effects of music are limited to lessening the bradykinesia of whole body movement or whether beneficial effects also extend to skilled movements of PD subjects. This question was addressed in the present study in which control and PD subjects were given a skilled reaching task that was performed with and without accompanying preferred musical pieces. Eye movements and limb use were monitored with biomechanical measures and limb movements were additionally assessed using a previously described movement element scoring system. Preferred musical pieces did not lessen limb and hand movement impairments as assessed with either the biomechanical measures or movement element scoring. Nevertheless, the PD patients with more severe motor symptoms as assessed by Hoehn and Yahr (HY) scores displayed enhanced visual engagement of the target and this impairment was reduced during trials performed in association with accompanying preferred musical pieces. The results are discussed in relation to the idea that preferred musical pieces, although not generally beneficial in lessening skilled reaching impairments, may normalize the balance between visual and proprioceptive guidance of skilled reaching.
- ItemMaking context memories independent of the hippocampus(Cold Spring Harbor Laboratory Press, 2009) Lehmann, Hugo; Sparks, Fraser T.; Spanswick, Simon C.; Hadikin, Crystal; McDonald, Robert J.; Sutherland, Robert J.We present evidence that certain learning parameters can make a memory, even a very recent one, become independent of the hippocampus. We confirm earlier findings that damage to the hippocampus causes severe retrograde amnesia for context memories, but we show that repeated learning sessions create a context memory that is not vulnerable to the damage. The findings demonstrate that memories normally dependent on the hippocampus are incrementally strengthened in other memory networks with additional learning. The latter provides a new account for patterns of hippocampal retrograde amnesia and how memories may become independent of the hippocampus.
- ItemHippocampus leads ventral striatum in reply of place-reward information(Public Library of Science, 2009) Lansink, Carien S.; Goltstein, Pieter M.; Lankelma, Jan V.; McNaughton, Bruce L.; Pennartz, Cyriel M. A.Associating spatial locations with rewards is fundamental to survival in natural environments and requires the integrity of the hippocampus and ventral striatum. In joint multineuron recordings from these areas, hippocampal–striatal ensembles reactivated together during sleep. This process was especially strong in pairs in which the hippocampal cell processed spatial information and ventral striatal firing correlated to reward. Replay was dominated by cell pairs in which the hippocampal ‘‘place’’ cell fired preferentially before the striatal reward-related neuron. Our results suggest a plausible mechanism for consolidating place-reward associations and are consistent with a central tenet of consolidation theory, showing that the hippocampus leads reactivation in a projection area.
- ItemObject/context-specific memory deficits associated with loss of hippocampal granule cells after adrenalectomy in rats(Cold Spring Harbor Laboratory Press, 2010) Spanswick, Simon C.; Sutherland, Robert J.Chronic adrenalectomy (ADX) causes a gradual and selective loss of granule cells in the dentate gyrus (DG) of the rat.Here, we administered replacement corticosterone to rats beginning 10wk after ADX. We then tested them in three discrimination tasks based on object novelty, location, or object/context association. Only during testing of the object/context association did ADX rats demonstrate deficits. These findings add to a body of evidence that the hippocampus is necessary when contextual information is important.We also confirm that memory deficits after chronic adrenalectomy are not a result of loss of corticosterone per se.
- ItemFactors influencing cerebral plasticity in the normal and injured brain(Frontiers Research Foundation, 2010) Kolb, Bryan; Teskey, G. Campbell; Gibb, Robbin L.An important development in behavioral neuroscience in the past 20 years has been the demonstration that it is possible to stimulate functional recovery after cerebral injury in laboratory animals. Rodent models of cerebral injury provide an important tool for developing such rehabilitation programs. The models include analysis at different levels including detailed behavioral paradigms, electrophysiology, neuronal morphology, protein chemistry, and epigenetics. A significant challenge for the next 20 years will be the translation of this work to improve the outcome from brain injury and disease in humans. Our goal in the article will be to synthesize the multidisciplinary laboratory work on brain plasticity and behavior in the injured brain to inform the development of rehabilitation programs.
- ItemEvolutionary divergence in brain size between migratory and resident birds(Public Library of Science, 2010) Sol, Daniel; Garcia, Nuria; Iwaniuk, Andrew N.; Davis, Katie; Meade, Andrew; Boyle, W. Alice; Szekely, TamasDespite important recent progress in our understanding of brain evolution, controversy remains regarding the evolutionary forces that have driven its enormous diversification in size. Here, we report that in passerine birds, migratory species tend to have brains that are substantially smaller (relative to body size) than those of resident species, confirming and generalizing previous studies. Phylogenetic reconstructions based on Bayesian Markov chain methods suggest an evolutionary scenario in which some large brained tropical passerines that invaded more seasonal regions evolved migratory behavior and migration itself selected for smaller brain size. Selection for smaller brains in migratory birds may arise from the energetic and developmental costs associated with a highly mobile life cycle, a possibility that is supported by a path analysis. Nevertheless, an important fraction (over 68%) of the correlation between brain mass and migratory distance comes from a direct effect of migration on brain size, perhaps reflecting costs associated with cognitive functions that have become less necessary in migratory species. Overall, our results highlight the importance of retrospective analyses in identifying selective pressures that have shaped brain evolution, and indicate that when it comes to the brain, larger is not always better.
- ItemA novel animal model of hippocampal cognitive deficits, slow neurodegeneration, and neuroregeneration(Hindawi Publishing, 2011) Spanswick, Simon C.; Lehmann, Hugo; Sutherland, Robert J.Long-term adrenalectomy (ADX) results in an extensive and speciﬁc loss of dentate gyrus granule cells in the hippocampus of adult rats. This loss of granule cells extends over a period of weeks to months and ultimately results in cognitive deﬁcits revealed in a number of tasks that depend on intact hippocampal function. The gradual nature of ADX-induced cell death and the ensuing deﬁcits in cognition resemble in some important respects a variety of pathological conditions in humans. Here, we characterize behavioural and cellular processes, including adult neurogenesis, in the rat ADX model.We also provide experimental evidence for a neurogenic treatment strategy by which the lost hippocampal cells may be replaced, with the goal of functional recovery in mind.
- ItemSuppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory(Public Library of Science, 2011) Sparks, Fraser T.; Lehmann, Hugo; Hernandez, Khadaryna; Sutherland, Robert J.Damage to the hippocampus (HPC) using the excitotoxin N-methyl-D-aspartate (NMDA) can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity) during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDAinduced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX), a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDAinduced, or no damage to the HPC at a recent (24 hours) or remote (5 weeks) time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories.
- ItemAnatomical specializations for nocturnality in a critically endangered parrot, the Kakapo (Strigops habroptilus)(Public Library of Science, 2011) Corfield, Jeremy R.; Gsell, Anna C.; Brunton, Dianne; Heesy, Christopher P.; Hall, Margaret I.; Acosta, Monica L.; Iwaniuk, Andrew N.The shift from a diurnal to nocturnal lifestyle in vertebrates is generally associated with either enhanced visual sensitivity or a decreased reliance on vision. Within birds, most studies have focused on differences in the visual system across all birds with respect to nocturnality-diurnality. The critically endangered Kakapo (Strigops habroptilus), a parrot endemic to New Zealand, is an example of a species that has evolved a nocturnal lifestyle in an otherwise diurnal lineage, but nothing is known about its’ visual system. Here, we provide a detailed morphological analysis of the orbits, brain, eye, and retina of the Kakapo and comparisons with other birds. Morphometric analyses revealed that the Kakapo’s orbits are significantly more convergent than other parrots, suggesting an increased binocular overlap in the visual field. The Kakapo exhibits an eye shape that is consistent with other nocturnal birds, including owls and nightjars, but is also within the range of the diurnal parrots. With respect to the brain, the Kakapo has a significantly smaller optic nerve and tectofugal visual pathway. Specifically, the optic tectum, nucleus rotundus and entopallium were significantly reduced in relative size compared to other parrots. There was no apparent reduction to the thalamofugal visual pathway. Finally, the retinal morphology of the Kakapo is similar to that of both diurnal and nocturnal birds, suggesting a retina that is specialised for a crepuscular niche. Overall, this suggests that the Kakapo has enhanced light sensitivity, poor visual acuity and a larger binocular field than other parrots. We conclude that the Kakapo possesses a visual system unlike that of either strictly nocturnal or diurnal birds and therefore does not adhere to the traditional view of the evolution of nocturnality in birds.
- ItemIdentification of bilateral changes in T1D1 expression in the 6-OHDA rat model of Parkinson's disease(Public Library of Science, 2011) Proft, Juliane; Faraji, Jamshid; Robbins, Jerrah C.; Zucchi, Fabiola C. R.; Zhao, Xiaoxi; Metz, Gerlinde A. S.; Braun, Janice E. A.Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra and the aggregation of a-synuclein into Lewy bodies. Existing therapies address motor dysfunction but do not halt progression of the disease. A still unresolved question is the biochemical pathway that modulates the outcome of protein misfolding and aggregation processes in PD. The molecular chaperone network plays an important defensive role against cellular protein misfolding and has been identified as protective in experimental models of protein misfolding diseases like PD. Molecular mechanisms underlying chaperone-neuroprotection are actively under investigation. Current evidence implicates a number of molecular chaperones in PD including Hsp25, Hsp70 and Hsp90, however their precise involvement in the neurodegenerative cascade is unresolved. The J protein family (DnaJ or Hsp40 protein family) has long been known to be important in protein conformational processes. We assessed sensory and motor function of control and PD rats and then evaluated the brain region-specific expression levels of select J proteins by Western analysis. Surprisingly, we observed a widespread 26 kDa breakdown product of the J protein, TID1, (tumorous imaginal discs, mtHsp40 or DnaJ3) in a 6-hydroxydopamine (6-OHDA) rat model of PD in which food handling, gait symmetry and sensory performance were impaired. Greater behavioral deficits were associated with lower TID1 expression. Furthermore, direct application of either 6- OHDA or MPP+ (1-methyl-4-phenylpyridinum) to CAD (CNS-derived catecholinaminergic neuronal cell line) cell cultures, reduced TID1 expression levels. Our results suggest that changes in cellular TID1 are a factor in the pathogenesis of PD by impeding functional and structural compensation and exaggerating neurodegenerative processes. In contrast, no changes were observed in CSPa, Hsp40, Hsp70, Hsc70 and PrPC levels and no activation of caspase3 was observed. This study links TID1 to PD and provides a new target for therapeutics that halts the PD progression.
- ItemContext, emotion, and the strategic pursuit of goals: interactions among multiple brain systems controlling motivated behavior(Frontiers Media, 2012) Gruber, Aaron J.; McDonald, Robert J.Motivated behavior exhibits properties that change with experience and partially dissociate among a number of brain structures. Here, we review evidence from rodent experiments demonstrating that multiple brain systems acquire information in parallel and either cooperate or compete for behavioral control. We propose a conceptual model of systems interaction wherein a ventral emotional memory network involving ventral striatum (VS), amygdala, ventral hippocampus, and ventromedial prefrontal cortex triages behavioral responding to stimuli according to their associated affective outcomes. This system engages autonomic and postural responding (avoiding, ignoring, approaching) in accordance with associated stimulus valence (negative, neutral, positive), but does not engage particular operant responses. Rather, this emotional system suppresses or invigorates actions that are selected through competition between goal-directed control involving dorsomedial striatum (DMS) and habitual control involving dorsolateral striatum (DLS). The hippocampus provides contextual speciﬁcityto the emotional system, and provides an information rich input to the goal-directed system for navigation and discriminations involving ambiguous contexts, complex sensory conﬁgurations, or temporal ordering. The rapid acquisition and high capacity for episodic associations in the emotional system may unburden the more complex goal-directed system and reduce interference in the habit system from processing contingencies of neutral stimuli. Interactions among these systems likely involve inhibitory mechanisms and neuromodulation in the striatum to form a dominant response strategy. Innate traits, training methods, and task demands contribute to the nature of these interactions, which can include incidental learning in non-dominant systems. Addition of these features to reinforcement learning models of decision-makingmay better aligntheoretical predictions with behavioral and neural correlates in animals.
- ItemGenomic and epigenomic responses to chronic stress involve miRNA-mediated programming(Public Library of Science, 2012) Babenko, Olena M.; Golubov, Andrey; Ilnytskyy, Yaroslav; Kovalchuk, Igor; Metz, Gerlinde A. S.Stress represents a critical influence on motor system function and has been shown to impair movement performance. We hypothesized that stress-induced motor impairments are due to brain-specific changes in miRNA and protein-encoding gene expression. Here we show a causal link between stress-induced motor impairment and associated genetic and epigenetic responses in relevant central motor areas in a rat model. Exposure to two weeks of mild restraint stress altered the expression of 39 genes and nine miRNAs in the cerebellum. In line with persistent behavioural impairments, some changes in gene and miRNA expression were resistant to recovery from stress. Interestingly, stress up-regulated the expression of Adipoq and prolactin receptor mRNAs in the cerebellum. Stress also altered the expression of Prlr, miR-186, and miR-709 in hippocampus and prefrontal cortex. In addition, our findings demonstrate that miR-186 targets the gene Eps15. Furthermore, we found an age-dependent increase in EphrinB3 and GabaA4 receptors. These data show that even mild stress results in substantial genomic and epigenomic changes involving miRNA expression and associated gene targets in the motor system. These findings suggest a central role of miRNA-regulated gene expression in the stress response and in associated neurological function.
- ItemExperience-dependent firing rate remapping generates directional selectivity in hippocampal place cells(Frontiers Research Foundation, 2012) Navratilova, Zaneta; Hoang, Lan T.; Schwindel, C. Daniela; Tatsuno, Masami; McNaughton, Bruce L.When rodents engage in irregular foraging in an open-field environment, hippocampal principal cells exhibit place-specific firing that is statistically independent of the direction of traverse through the place field. When the path is restricted to a track, however, in-field rates differ substantially in opposite directions. Frequently, the representations of the track in the two directions are essentially orthogonal. We show that this directionally selective firing is not hard-wired, but develops through experience-dependent plasticity. During the rats' first pass in each direction, place fields were highly directionally symmetric, whereas over subsequent laps, the firing rates in the two directions gradually but substantially diverged. We conclude that, even on a restricted track, place cell firing is initially determined by allocentric position, and only later, the within-field firing rates change in response to differential sensory information or behavioral cues in the two directions. In agreement with previous data, place fields near local cues, such as textures on the track, developed less directionality than place fields on a uniform part of the track, possibily because the local cues reduced the net difference in sensory input at a given point. Directionality also developed in an open environment without physical restriction of the animal's path, when rats learned to run along a specified path. In this case, directionality developed later than on the running track, only after the rats began to run in a stereotyped manner. Although the average population firing rates exhibited little if any change over laps in either direction, the direction-specific firing rates in a given place field were up-or-down-regulated with about equal probability and magnitude, which was independent in the two directions, suggesting some form of competitive mechanism (e.g., LTP/LTD) acting coherently on the set of synapses conveying external information to each cell.