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Hippocampal Subregions (hippocampal + subregion)
Selected AbstractsDose-dependent long-term effects of Tat in the rat hippocampal formation: A design-based stereological studyHIPPOCAMPUS, Issue 4 2010Sylvia Fitting Abstract The human immunodeficiency virus type 1 (HIV-1) protein transactivator of transcription (Tat) is believed to play a critical role in mediating central nervous system (CNS) pathology in pediatric HIV-1 infection. Long-term neurotoxicity was investigated in a design-based stereology study following intrahippocampal injection of Tat on postnatal day (P)10, a time period that approximates the peak in the rats' rate of brain growth and mimics clinical HIV-1 CNS infection at labor/delivery. The goal was to examine the impact of P10 intrahippocampal Tat injection on the anatomy of the adult hippocampus (5 month) to gain a better understanding about how timing of infection influences the rate of progression of pediatric HIV-1 infection [cf. Fitting et al. (2008a) Hippocampus 18:135,147]. Male P10 Sprague-Dawley rats were bilaterally injected with vehicle or one of three different doses of Tat (5, 25, or 50 ,g). Unbiased stereological estimates were used to quantify total neuron number (Nissl stain) in five major subregions of the rat hippocampus: granular layer (GL), hilus of the dentate gyrus (DGH), cornu ammonis fields (CA)2/3, CA1, and subiculum (SUB). Glial cells (astrocytes and oligodendrocytes) were quantified in the DGH and SUB. No significant reduction of neuron number was noted for any of the five hippocampal subregions, in contrast to the very prominent reductions reported when Tat was administered on P1 [Fitting et al. (2008a) Hippocampus 18:135,147]. However, for glial cells, the number of astrocytes in the DGH and SUB as well as the number of oligodendrocytes in the DGH were linear dose dependently increased as a function of dose of Tat. In conjunction with previous stereological research [Fitting et al., (2008a) Hippocampus 18:135,147], the present data suggest that variability in the progression of pediatric HIV/acquired immunodeficiency syndrome (AIDS) may be better understood with the knowledge of the factor of timing of HIV-1 CNS infection. © 2009 Wiley-Liss, Inc. [source] Lesions of the mammillary body region alter hippocampal movement signals and theta frequency: Implications for path integration modelsHIPPOCAMPUS, Issue 9 2008Patricia E. Sharp Abstract Cells throughout the hippocampal formation are involved in processing spatial information. These same cells also show an influence of locomotor activity, and these movement signals are thought to be critical for the path integration abilities of these cells. Nuclei in the mammillary region provide ascending influences to the hippocampal formation and have been implicated in influencing both hippocampal spatial and theta signals. Here, we report the effects of mammillary lesions on movement-related signals in several hippocampal subregions. We find first, as predicted by earlier work, these lesions cause an approximately 1 Hz reduction in the frequency of theta modulation of cell firing. According to recent theoretical work, this might, in turn, be expected to influence the size of hippocampal place fields. Our data do not confirm this prediction for any of the hippocampal regions examined. Second, we report lesion effects on the relationship between firing rate and running speed for the hippocampal cells. These lesions caused a reduction in both the slope and intercept of rate-by-speed functions for cells in the hippocampus and postsubiculum. Surprisingly, cells in subiculum showed an opposite effect, so that the excitatory influence of locomotion was enhanced. Path integration theories predict that the speed at which path integration occurs is related to the strength of this movement signal. In remarkable accordance with this prediction, we report that the timing of the place cell signals is slowed following mammillary lesions for hippocampal and postsubicular cells, but, in contrast, is speeded up for subicular cells. In fact, the timing for place signals across lesion condition and brain region is predicted by a single linear function which relates timing to the strength of the running speed signal. Thus, these data provide remarkable support for some aspects of current path integration theory, while posing a challenge for other aspects of these same theories. © 2008 Wiley-Liss, Inc. [source] Changes in rat hippocampal CA1 synapses following imipramine treatmentHIPPOCAMPUS, Issue 7 2008Fenghua Chen Abstract Neuronal plasticity in hippocampus is hypothesized to play an important role in both the pathophysiology of depressive disorders and the treatment. In this study, we investigated the consequences of imipramine treatment on neuroplasticity (including neurogenesis, synaptogenesis, and remodelling of synapses) in subregions of the hippocampus by quantifying number of neurons and synapses. Adult male Sprague-Dawley rats were injected with imipramine or saline (i.p.) daily for 14 days. Unbiased stereological methods were used to quantify the number of neurons and synapses. No differences in the volume and number of neurons of hippocampal subregions following imipramine treatment were found. However, the number and percentage of CA1 asymmetric spine synapses increased significantly and, conversely, the percentage of asymmetric shaft synapses significantly decreased in the imipramine treated group. Our results indicate that administration of imipramine for 14 days in normal rats could significantly increase the excitatory spine synapses, and change the relative distribution of spine and shaft synapses. We speculate that the present findings may be explained by the establishment of new synaptic connections and by remodelling or transformation of existing synapses. © 2008 Wiley-Liss, Inc. [source] Synaptic protein expression in the medial temporal lobe and frontal cortex following chronic bilateral vestibular lossHIPPOCAMPUS, Issue 5 2008Matthew Goddard Abstract Several studies have reported that bilateral vestibular deafferentation (BVD) results in the disruption of place cell function and theta activity in the hippocampus. Recent magnetic resonance imaging (MRI) studies in humans demonstrated that bilateral but not unilateral vestibular loss is associated with a bilateral atrophy of the hippocampus. In this study we investigated whether BVD in rats resulted in changes in the expression of four proteins related to neuronal plasticity, synaptophysin, SNAP-25, drebrin and neurofilament-L, in the hippocampal subregions (CA1, CA2/3, the DG) and the entorhinal (EC), perirhinal (PRC) and frontal cortices (FC), using western blotting. At 6 months following BVD, there were no significant differences in the expression of synaptophysin in any region. There were also no significant differences in SNAP-25 expression in CA1, CA2/3, EC, PRC, or the FC; however, there was a significant increase in SNAP-25 expression in the DG compared to sham controls. Drebrin A and E expression was significantly reduced in the EC and drebrin A was significantly reduced in the FC of BVD animals. NF-L expression was not significantly different in CA1, CA2/3, DG, EC, or the PRC. However, its expression was significantly reduced in the FC of BVD animals. These data suggest that circumscribed neurochemical changes in SNAP-25, drebrin and NF-L expression occur in the DG, EC, and the FC over 6 months following BVD. © 2008 Wiley-Liss, Inc. [source] Regional differences in hippocampal PKA immunoreactivity after training and reversal training in a spatial Y-maze taskHIPPOCAMPUS, Issue 5 2007Robbert Havekes Abstract It is suggested that the hippocampus functions as a comparator by making a comparison between the internal representation and actual sensory information from the environment (for instance, comparing a previously learned location of a food reward with an actual novel location of a food reward in a Y-maze). However, it remains unclear to what extent the various hippocampal regions contribute to this comparator function. One of the proteins known to be crucially involved in the formation of hippocampus-dependent long-term memory is the adenosine 3,,5, cyclic monophosphate dependent protein kinase (PKA). Here, we examined region-specific changes in immunoreactivity (ir) of the regulatory II,,, subunits of PKA (PKA RII,,,-ir) in the hippocampus during various stages of spatial learning in a Y-maze reference task. Thereafter, we compared changes in hippocampal PKA RII,,,-ir induced by training and reversal training in which the food reward was relocated to the previously unrewarded arm. We show that: (1) There was a clear correlation between behavioral performance and elevated PKA RII,,,-ir during the acquisition phase of both training and reversal training in area CA3 and dentate gyrus (DG), (2) PKA RII,,,-ir was similarly enhanced in area CA1 during the acquisition phase of reversal training, but did not correlate with behavioral performance, (3) PKA RII,,,-ir did not change during training or reversal training in the subiculum (SUB), (4) No changes in PKA RII,,, protein levels were found using Western blotting, and (5) AMPA receptor phosphorylation at serine 845 (S845p; the PKA site on the glutamate receptor 1 subunit (GluR1)), was enhanced selectively during the acquisition phase of reversal training. These findings reveal that training and reversal training induce region-specific changes in hippocampal PKA RII,,,-ir and suggest a differential involvement of hippocampal subregions in match-mismatch detection in case of Y-maze reference learning. Alterations in AMPA receptor regulation at the S845 site seems specifically related to the novelty detector function of the hippocampus important for match-mismatch detection. © 2007 Wiley-Liss, Inc. [source] Dissociating hippocampal subregions: A double dissociation between dentate gyrus and CA1HIPPOCAMPUS, Issue 6 2001Paul E. Gilbert Abstract This study presents a double dissociation between the dentate gyrus (DG) and CA1. Rats with either DG or CA1 lesions were tested on tasks requiring either spatial or spatial temporal order pattern separation. To assess spatial pattern separation, rats were trained to displace an object which covered a baited food-well. The rats were then allowed to choose between two identical objects: one covered the same well as the sample phase object (correct choice), and a second object covered a different unbaited well (incorrect choice). Spatial separations of 15,105 cm were used to separate the correct object from the incorrect object. To assess spatial temporal order pattern separation, rats were allowed to visit each arm of a radial eight-arm maze once in a randomly determined sequence. The rats were then presented with two arms and were required to choose the arm which occurred earliest in the sequence. The choice arms varied according to temporal separation (0, 2, 4, or 6) or the number of arms that occurred between the two choice arms in the sample phase sequence. On each task, once a preoperative criterion was reached, each rat was given either a DG, CA1, or control lesion and then retested. The results demonstrated that DG lesions resulted in a deficit on the spatial task but not the temporal task. In contrast, CA1 lesions resulted in a deficit on the temporal task but not the spatial task. Results suggest that the DG supports spatial pattern separation, whereas CA1 supports temporal pattern separation. Hippocampus 2001;11:626,636. © 2001 Wiley-Liss, Inc. [source] Redefining the boundaries of the hippocampal CA2 subfield in the mouse using gene expression and 3-dimensional reconstructionTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2005Edward S. Lein Abstract The morphology of neurons in the main divisions of the hippocampal complex allow the easy identification of granule cells in the dentate gyrus and pyramidal cells in the CA1 and CA3 regions of Ammon's horn. However, neurons in the CA2 subfield have been much more difficult to reliably identify. We have recently identified a set of genes whose expression is restricted to either the dentate gyrus, CA1, CA2, or CA3. Here we show that these genes have an essentially nonoverlapping distribution throughout the entire septotemporal extent of the hippocampus. 3-Dimensional reconstruction of serial sections processed for in situ hybridization of mannosidase 1, alpha (CA1), bcl-2-related ovarian killer protein (CA3), and Purkinje cell protein 4 (dentate gyrus + CA2) was used to define the boundaries of each subregion throughout the entire hippocampus. The boundaries observed for these three genes are recapitulated across a much larger set of genes similarly enriched in specific hippocampal subregions. The extent of CA2 defined on the basis of gene expression is somewhat larger than that previously described on the basis of structural anatomical criteria, particularly at the rostral pole of the hippocampus. These results indicate that, at least at the molecular level, there are robust, consistent genetic boundaries between hippocampal subregions CA1, CA2, CA3, and the dentate gyrus, allowing a redefinition of their boundaries in order to facilitate functional studies of different neuronal subtypes in the hippocampus. J. Comp. Neurol. 485:1,10, 2005. © 2005 Wiley-Liss, Inc. [source] Glutathione peroxidase activity modulates recovery in the injured immature brain,ANNALS OF NEUROLOGY, Issue 5 2009Kyoko Tsuru-Aoyagi MD Objective Mice subjected to traumatic brain injury at postnatal day 21 show emerging cognitive deficits that coincide with hippocampal neuronal loss. Here we consider glutathione peroxidase (GPx) activity as a determinant of recovery in the injured immature brain. Methods Wild-type and transgenic (GPxTg) mice overexpressing GPx were subjected to traumatic brain injury or sham surgery at postnatal day 21. Animals were killed acutely (3 or 24 hours after injury) to assess oxidative stress and cell injury in the hippocampus or 4 months after injury after behavioral assessments. Results In the acutely injured brains, a reduction in oxidative stress markers including nitrotyrosine was seen in the injured GPxTg group relative to wild-type control mice. In contrast, cell injury, with marked vulnerability in the dentate gyrus, was apparent despite no differences between genotypes. Magnetic resonance imaging demonstrated an emerging cortical lesion during brain maturation that was also indistinguishable between injured genotypes. Stereological analyses of cortical volumes likewise confirmed no genotypic differences between injured groups. However, behavioral tests beginning 3 months after injury demonstrated improved spatial memory learning in the GPxTg group. Moreover, stereological analysis within hippocampal subregions demonstrated a significantly greater number of neurons within the dentate of the GPx group. Interpretation Our results implicate GPx in recovery of spatial memory after traumatic brain injury. This recovery may be attributed, in part, to a reduction in early oxidative stress and selective, long-term sparing of neurons in the dentate. Ann Neurol 2009;65:540,549 [source] | ||||||||||