Abstract: The Morris water maze is an experimental procedure in which animals learn to escape swimming in a pool using environmental cues. Despite its success in neuroscience and psychology for studying spatial learning and memory, the exact mnemonic and navigational demands of the task are not well understood. Here, we provide a mathematical model of rat swimming dynamics on a behavioural level. The model consists of a random walk, a heading change and a feedback control component in which learning is reflected in parameter changes of the feedback mechanism. The simplicity of the model renders it accessible and useful for analysis of experiments in which swimming paths are recorded. Here, we used the model to analyse an experiment in which rats were trained to find the platform with either three or one extramaze cue. Results indicate that the 3-cues group employs stronger feedback relying only on the actual visual input, whereas the 1-cue group employs weaker feedback relying to some extent on memory. Because the model parameters are linked to neurological processes, identifying different parameter values suggests the activation of different neuronal pathways.
Abstract: The perirhinal cortex is located in a pivotal position to influence the flow of information into and out of the hippocampal formation. In this review, we examine the anatomical, physiological and functional properties of the rat perirhinal cortex. Firstly, we review the properties of the perirhinal cortex itself, we describe how it can be separated into two distinct subregions and consider how it differs from other neighbouring regions in terms of cell type, cellular organisation and its afferent and efferent projections. We review the forms of neurotransmission present in the perirhinal cortex and the morphological, electrophysiological and plastic properties of its neurons. Secondly, we review the perirhinal cortex in the context of its connections with other brain areas; focussing on the projections to cortical, subcortical and hippocampal/parahippocampal regions. Particular attention is paid the anatomical and electrophysiological properties of these projections. Thirdly, we review the main functions of the perirhinal cortex; its roles in perception, recognition memory, spatial and contextual memory and fear conditioning are explored. Finally, we discuss the idea of anatomical, electrophysiological and functional segregation within the perirhinal cortex itself and as part of a hippocampal-parahippocampal network and suggest that understanding this segregation is of critical importance in understanding the role and contributions made by the perirhinal cortex in general.
Abstract: Immediate early gene (IEG) imaging offers a sophisticated approach to study the neural basis of learning in the brain. Demonstrating a high degree of spatial resolution, the activation of entire neuronal ensembles at multiple time-points can be observed. IEG imaging techniques have revealed a high level of responsiveness to spatial exploration within the hippocampus and other brain regions. The pattern of IEG activation is tightly linked with specific environments and appears to be involved in the subsequent consolidation of spatial information. This incidental learning is a potential confounding factor in studies investigating the neural correlates of spatial learning in both the radial arm maze and water maze. Although both these tasks increase hippocampal IEG expression from baseline levels, where control groups have fully explored the apparatus in the absence of task demands, or where animals are performing a non-spatial task, IEG expression in this region is comparable to spatially trained groups. However, the relationship between IEG expression and task performance, as well as the pattern of brain activation has been shown to differentiate between experimental and control groups. Inconsistencies between training protocols appear to contribute to the discrepancies between reported findings, and the role of IEG expression in the retention of spatial memory tasks remains unclear. Further investigation of the time course and dynamics of IEG expression during learning and retention is required to fully interpret observed results.
Abstract: The ability of a synapse to be modulated both positively and negatively may be considered as a plausible model for the formation of learning and memory. The CA1 to perirhinal cortex projection is one of the multiple hippocampal-neocortical projections considered to be crucially involved in memory consolidation. We and others have previously demonstrated the ability of this projection to undergo long-term potentiation (LTP), however it is currently unknown whether the CA1-perirhinal projection can also be modified negatively (i.e. demonstrate long-term depression (LTD)). Here we investigate whether the CA1 to perirhinal projection in vivo in the anaesthetised animal shows a frequency-dependent pattern of synaptic plasticity that is coupled with brain-derived neurotrophic factor (BDNF) expression. Five groups of animals were used and each group underwent one of five different stimulation protocols (1 Hz, 5 Hz, 10 Hz, 50 Hz or 100 Hz) followed by post-stimulation recordings at baseline stimulation intensity (0.05 Hz) for 1h. Paired-pulse facilitation (PPF) recordings were taken both during baseline and 1h post-stimulation across six inter-pulse intervals (IPIs). Following all experiments, tissue samples were taken from area CA1 and perirhinal cortex from both the unstimulated and stimulated hemispheres of each brain and analysed for BDNF. Results indicated that LTP was observed following 50 Hz and 100 Hz HFS but LTD was not observed following any low-frequency stimulation. Pre- and post-stimulation PPF recordings revealed no difference for any of the stimulation frequencies, suggesting that the plasticity observed may involve a post- rather than a presynaptic mechanism. Finally, changes in BDNF were positively correlated with stimulation frequency in the area CA1 but the same pattern was not observed in the perirhinal cortex. These findings suggest that the CA1 to perirhinal cortex projection is electrophysiologically excitatory in nature and that changes in BDNF levels in this projection may not be predictive of changes in synaptic plasticity.
Abstract: The CA1 to perirhinal cortex projection is one of multiple hippocampal-neocortical projections considered to be involved in memory consolidation. This projection has been shown to sustain long-term potentiation (LTP) following stimulation of CA1. Here we examined the pharmacological properties underpinning the plasticity observed in this projection. A stimulating electrode was inserted into the area CA1 and a recording electrode was inserted into the perirhinal cortex of urethane-anaesthetised Wistar rats. Rats (n=6 in each drug group) were administered with either saline (0.09%), MK-801 (NMDA antagonist; 0.1 mg/kg) or CNQX (AMPA/kainate antagonist; 1.5 mg/kg). Baseline recordings were made for 10 min by stimulating area CA1 (0.05 Hz stimulation protocol). High-frequency stimulation (HFS; 250 Hz) was performed and post-HFS fEPSP recordings were made for 1 h (0.05 Hz, as above). Baseline and post-HFS paired-pulse facilitation (PPF) recordings were performed across six different interpulse intervals. CA1 and perirhinal cortex tissue samples were taken from the stimulated and unstimulated hemispheres of each rat brain and analysed using a brain-derived neurotrophic factor (BDNF) ELISA. Results indicate that LTP was induced in the saline and MK-801 groups but not in the CNQX group; fEPSPs in the latter group rapidly returned to baseline levels following a short period of post-tetanic potentiation. Drug treatment and HFS had no effect on PPF levels. Drug treatment significantly reduced concentrations of both CA1 and perirhinal BDNF and prevented stimulation-induced increases in BDNF in CA1. This molecular and electrophysiological data suggests that LTP in the CA1-perirhinal cortex projection may require activation of postsynaptic AMPA/kainate receptors in order to sustain LTP.
Abstract: Several factors can influence allocentric navigation in the Morris water maze (MWM), including the number of available distal visual cues. Using in-depth analytical measures investigating platform-based and swimming behaviour, we examine and compare animals exposed to either one or three distal visual cues during MWM acquisition. We demonstrate that, although animals exposed to one cue can acquire the task as well as those in a multiple cue condition, several subtle differences between the groups' swimming behaviours are noted. Both groups actively use cues to guide them to the platform, but changing the number of cues alters the animals' patterns of behaviour, wherein exposure to a single cue leads to a simpler strategy in which the cue appears to act as a beacon for navigation.
Abstract: High-density event-related potentials (ERPs) were recorded during an object recognition task which involved task-irrelevant changes in the location of studied objects. Participants categorised objects as studied or novel while data were analysed to ascertain the effect of the location changes on performance and waveform topography. Our results indicate that humans can classify objects faster and more accurately when using implicit spatial memory. Individual differences observed in object recognition proficiency were absent if objects were presented in their 'correct' location. In a second experiment we replicated the behavioural findings while manipulating viewpoint to discount scene recognition as an underlying factor. We propose a model which includes activation of the right medial temporal lobe prior to P300 elicitation to account for the prophylactic effect of implicit processing on object recognition. Hemispheric differences in parietal componentry dependant on sex of participant were also observed and are discussed in relation to differential strategies.
Abstract: From insects to humans, successful navigation relies on retained representations of spatial relations. These representations are thought to depend on the hippocampal formation, particularly those that are independent of the navigator (allocentric representations). The Morris water maze is a simple and popular task often used to assess spatial navigation. But how animals navigate toward and retain information regarding the location of the goal in this task remains unclear. We provide a comprehensive account of how the water maze is accomplished behaviourally. Our findings suggest that animals solve the task using distal cues via an initial view-matching strategy that is supported by egocentric guidance. Through increased training, however, an emergence of an egocentric-guiding strategy combined with the animal's greater ability to infer the hidden platform's location (via allocentric extrapolation) emerges. We also demonstrate that behavioural changes, towards a more allocentric strategy, are reflected in increases in hippocampal brain-derived neurotrophic factor.
Abstract: Animals can use both allocentric and egocentric strategies to learn a spatial task. Our results suggest that allocentric cues are more dominant than idiothetic cues in guiding navigation. Animals do not necessarily learn an egocentric strategy automatically, instead they probably hold just one solution to any particular task at a time until forced to learn an alternative strategy. Further, with overtraining animals do not always switch from allocentric to an egocentric learning strategy perhaps challenging suggestions of a stored hierarchy of strategies.
Abstract: Hippocampal protein synthesis is dependent upon a number of different molecular and cellular mechanisms that act together to make previously labile memories more stable and resistant to disruption. Both brain-derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase (ERK) are known to play an important role in protein synthesis-dependent memory consolidation, via the mitogen-activated protein-kinase (MAP-K) signaling pathway during the transcription phase of protein synthesis. The current study investigates the influence of protein synthesis inhibition (PSI) by cycloheximide on spatial learning and memory. In an initial experiment, the authors utilized two doses of cycloheximide (0.5 mg/kg and 1.0 mg/kg, intraperitoneally) to determine the dose at which long-term (>24 hours) memories are impaired. A second experiment was designed to investigate the effect of PSI on the formation of cue-platform associations in the watermaze, and on BDNF and ERK expression in the hippocampus. At the higher dose (1.0 mg/kg) cycloheximide resulted in impaired retention of the water maze. BDNF and ERK expression was also down-regulated in animals injected with this dose of cycloheximide. Our results demonstrate a role of protein synthesis in spatial memory retention, along with a possible relationship between protein synthesis and hippocampal BDNF/ERK expression.
Abstract: The hippocampal formation (HF) is a brain structure critically involved in memory formation. Two major pathways have been identified in the rat; one projection targets the hippocampus via perirhinal cortex and lateral entorhinal cortex (LEC) while another targets the hippocampus via postrhinal cortex and medial entorhinal cortex (MEC). Areas CA1 and subiculum constitute major output structures of HF and target many cortical structures including EC. These return projections are also anatomically segregated with distinct regions of CA1 and subiculum projecting to either the LEC or MEC. We have previously demonstrated that the projections from CA1 and subiculum to the EC are capable of sustaining short- and long-term plastic changes. Here we detail a physiological topography that exists along the hippocampal output projections, equating well with the known anatomy. Specifically, field excitatory postsynaptic potential (fEPSP) responses in LEC are stronger following distal CA1 and proximal subiculum stimulation, compared to either proximal CA1 or distal subiculum stimulation. In addition, fEPSP responses in MEC are stronger following proximal CA1 stimulation compared to distal CA1. We also demonstrate that the distal CA1-LEC, proximal CA1-MEC and proximal subiculum-LEC projections are all capable of frequency-dependent plastic effects that shift the response from LTD to LTP. In addition, responses in distal CA1-LEC projection seem to show metaplastic capabilities. We discuss the possibility of dissociation between LEC and MEC projections, which may suggest two functional circuits from the HF to the cortex and may have implications in information processing, memory research and hippocampal seizure spread to the cortex.
Abstract: Visuomotor association learning involves learning to make a motor response to an arbitrary visual stimulus. This learning is essential for visual search and discrimination performance and is reliant upon a well-defined neural circuit in the brain that includes the prefrontal cortex and the hippocampal formation. In the present study, we investigated the possible role of attentional processes during such learning using dual-task interference. A motor, verbal, or perceptual concurrent task was performed during the learning/training block of a simple visual discrimination task. Contrary to expectation, the dual-task groups showed improved learning and learning-dependent performance compared with untrained control and non-dual-task trained groups. A second experiment revealed that this effect did not appear to be due to increased arousal level; the inclusion of alerting tones during learning did not result in facilitation. These findings suggest that the engagement of attention, but not arousal, during the acquisition of a visuomotor association can facilitate this learning and its expression.
Abstract: Lipopolysaccharide (LPS) is a potent endotoxin, which produces "sickness behaviours" including loss of weight, loss of interest in food and decreased exploration. LPS has also been shown in some studies to cause deficits in various learning and memory abilities, while in others these LPS-induced learning impairments have been attributed to performance-related deficits rather than learning deficits per se. Here, we use the novelty-preference paradigm, a task that minimises performance-related factors such as motivation, in an attempt to extract and examine the effects of LPS on spatial learning. In addition, some studies have indicated that the anti-inflammatory cytokine Interleukin-10 (IL-10) can alleviate some of the symptoms induced by LPS. Here, we also examine the effect of IL-10 on feeding, motor and learning behaviours. We demonstrate that a single injection of LPS does produce a lack of interest in food and weight loss; LPS, however, does not impair habituation in the novelty-preference paradigm. Furthermore, co-injection of IL-10 with LPS does not attenuate the LPS-induced effects of weight loss and lack of food intake. Interestingly, a single injection of IL-10 produces abnormal patterns of exploration, a general increase in activity and abnormal patterns of habituation.
Abstract: The hippocampus communicates with the neocortex via the entorhinal cortex. These areas are thought to be critically involved in the consolidation of memories. The hippocampus is considered to be the site of association of sensory information, which is then laid down for long-term storage in the neocortex. We examined the projection from the subiculum to the entorhinal cortex to determine whether it could function to transfer this hippocampally-processed information to the neocortex. Following stimulation in the subiculum we demonstrate a negative-going deflection followed by a positive-going deflection in the entorhinal cortex. This projection is capable of short-term plastic changes in the form of PPF. FIn addition, we demonstrate that long-term synaptic changes in the form of LTP and LTD could be sustained for at least 30min on this pathway. Finally we show that PPF changes after LTP and LTD, suggesting that a presynaptic mechanism may be involved in both of these pathways.
Abstract: Peripheral administration of lipopolysaccharide (LPS), a potent bacterial endotoxin, can cause a variety of central effects, including production of cytokines and cyclooxygenases in the brain, as well as peripheral increases in corticosterone. These, in turn, may contribute to neuroimmune-induced neurocognitive deficits. We show here LPS causes deficits in hippocampal-dependent spatial learning in the water maze but that treatment with ibuprofen, a broad-spectrum cyclooxygenase inhibitor, reverses the deficits induced in spatial learning by LPS. We also show that LPS causes an impairment in the induction of long-term potentiation in the dentate gyrus in vivo, a major contemporary model of learning and memory. No differences were found in corticosterone levels in trunk blood but we find a decrease in brain-derived neurotrophic factor (BDNF) expression in LPS group compared to saline controls. Paradoxically compared to the behavioral findings treatment with ibuprofen does not attenuate the LPS-induced impairment in LTP or BDNF concentration in tetanized tissue.
Abstract: The object displacement task is a popular tool used to investigate spatial learning and memory. However, little attention has previously been given to long-term retention of spatial information following habituation to this task. Furthermore, the role of both proximal and distal cues in this type of passive retention of spatial information is controversial. In Study 1, we examined habituation in the object displacement task across 4 days and examined reactivity to spatial change 7 days post-acquisition. We found that rats habituated rapidly to the environment and retained this environment for the 7 days. Furthermore, this experiment shows that both proximal and distal spatial cues are important in the encoding of the environment during object displacement learning task. In Study 2, we examined the effect of overshadowing and demonstrate that proximal visual spatial cues can overshadow distal spatial cues if a conflict arises between both set.
Abstract: Spatial learning in the water maze is thought to rely both on distal cues and vestibular information [Aggleton JP, Vann SD, Oswald CJP, Good M. Identifying cortical inputs to the rat hippocampus that subserves allocentric spatial processes: a simple problem with a complex answer. Hippocampus 2000;10:466-74; Pearce JM. Animal learning and cognition: an introduction. UK: Psychology Press; 1997]. Experiment 1 demonstrates that while water maze retention relies primarily on cue-platform based associations, this strategy is not precise, as animals tend to focus at the side of the pool. In experiment 2, we demonstrate that vestibular rotation eliminates this inaccuracy. These experiments highlight the importance of both cue and vestibular information for accurate retention of the water maze.
Abstract: The hippocampus communicates with the neocortex via the entorhinal cortex and is thought to be critically involved in the consolidation of memories. This paper contains in vivo evidence of a projection from the hippocampal area CA1 to the entorhinal cortex. Current theories of memory formation suggest that the backprojections from the hippocampus to the neocortex should undergo some form of plastic change in order that memories become consolidated. Paired-pulse facilitation (PPF) and long-term potentiation (LTP) are forms of short- and long-term plasticity, respectively. We show that the CA1 to entorhinal cortex projection is capable of sustaining PPF over a wide range of stimulus intervals. In addition we demonstrate that following high frequency stimulation of this pathway the evoked response in the entorhinal cortex remains potentiated for at least 30 min. Finally, we demonstrate that PPF changes following LTP depending on the initial ratio of PPF, suggesting that LTP expression on this pathway may contain a presynaptic component. These findings should provide insight into the hippocampal function in memory formation.
Abstract: The current study aimed to test a Relational Frame Theory (RFT) model of analogical reasoning based on the relating of derived same and derived difference relations. Experiment 1 recorded reaction time measures of similar-similar (e.g., "apple is to orange as dog is to cat") versus different-different (e.g., "he is to his brother as chalk is to cheese") derived relational responding, in both speed-contingent and speed-noncontingent conditions. Experiment 2 examined the event-related potentials (ERPs) associated with these two response patterns. Both experiments showed similar-similar responding to be significantly faster than different-different responding. Experiment 2 revealed significant differences between the waveforms of the two response patterns in the left-hemispheric prefrontal regions; different-different waveforms were significantly more negative than similar-similar waveforms. The behavioral and neurophysiological data support the RFT prediction that, all things being equal, similar-similar responding is relationally "simpler" than, and functionally distinct from, different-different analogical responding. The ERP data were fully consistent with findings in the neurocognitive literature on analogy. These findings strengthen the validity of the RFT model of analogical reasoning and supplement the behavior-analytic approach to analogy based on the relating of derived relations.
Abstract: Derived equivalence relations, it has been argued, provide a behavioral model of semantic or symbolic meaning in natural language, and thus equivalence relations should possess properties that are typically associated with semantic relations. The present study sought to test this basic postulate using semantic priming. Across three experiments, participants were trained and tested in two 4-member equivalence relations using word-like nonsense words. Participants also were exposed to a single- or two-word lexical decision task, and both direct (Experiment 1) and mediated (Experiments 2 and 3) priming effects for reaction times and event-related potentials were observed within but not across equivalence relations. The findings support the argument that derived equivalence relations provides a useful preliminary model of semantic relations.
Abstract: The ability of an organism to develop, maintain, and act upon an abstracted internal representation of spatially extensive environments can provide an increased chance in ensuring that organism's survival. Here, we propose a neurocognitive model of spatial representation describing how several different processes interact and segregate the differing types of information used to produce a unified cognitive map. This model proposes that view-based egocentric and vestibulomotor translational information are functionally and anatomically separate, and that these parallel systems result in independent, but interacting, models within a neurocognitive map of space. In this context, we selectively review relevant portions of the large literature, addressing the establishment and operation of such spatial constructs in humans and the brain systems that underpin them, with particular reference to the hippocampal formation (HF). We present a reinterpretation of the types of knowledge used in the formation of this spatial construct, the processes that act upon this information, the nature of the final spatial representation, and describe how these universal concepts relate to the proposed model of spatial processing. The relevant experimental paradigms used to examine the neural basis of spatial representation and the main findings from previous research are also briefly presented. Finally, we detail a series of testable theoretical, behavioral, and anatomical predictions made by the model.
Abstract: Research has focused mainly on the acquisition phase of spatial tasks, while retention has been relatively ignored. In three experiments, we determine the type of information that is retained in spatial memory using the water maze task. In experiment 1, we demonstrate that by rotating the distal cues 180 degrees post-acquisition Wistar rats search in the opposite area to where the platform should be. This search continues for a maximum of 30 s. We then demonstrate (experiment 2) that by rotating the starting position (180 degrees post-acquisition) animals remain at the starting-point for 10 s. They then commence searching in the platform area. In experiment 3, we demonstrate that rotations of distal cues and starting position post-acquisition impair retention of the platform's location. We suggest that the association between the configuration of distal cues and platform location is retained in memory but the association is fragile and sensitive to disruption.
Abstract: Cyclooxygenase (COX), which is present in two isoforms (COX1 and 2), synthesizes prostaglandins from arachidonic acid; it plays a crucial role in inflammation in both central and peripheral tissues. Here, we describe its role in synaptic plasticity and spatial learning in vivo via an effect on brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2; both measured by Elisa). We found that broad-spectrum COX inhibition (BSCI) inhibits the induction of long-term potentiation (LTP; the major contemporary model of synaptic plasticity), and causes substantial and sustained deficits in spatial learning in the watermaze. Increases in BDNF and PGE2 following spatial learning and LTP were also blocked. Importantly, 4 days of prior exercise in a running wheel increased endogenous BDNF levels sufficiently to reverse the BSCI of LTP and spatial learning, and restored a parallel increase in LTP and learning-related BDNF and PGE2. In control experiments, we found that BSCI had no effect on baseline synaptic transmission or on the nonhippocampal visible-platform task; there was no evidence of gastric ulceration from BSCI. COX2 is inhibited by glucorticoids; there was no difference in blood corticosterone levels as measured by radioimmunoassay in any condition. Thus, COX plays a previously undescribed, permissive role in synaptic plasticity and spatial learning via a BDNF-associated mechanism.
Abstract: The Morris water maze and the object displacement task are two popular tools used to investigate spatial learning and memory. Research has focused mainly on the acquisition of spatial tasks while little attention has been given to the retention phase. We examined the effects of different training procedures on retention of the water maze and also reactivity to spatial change in the object displacement task 7 days post-acquisition. We found that massed-trained animals were impaired on retention of the water maze compared to those animals that had received spaced-training. We also found that the massed-trained animals habituated readily to their environment in the object displacement task while the spaced-trained group did not. Furthermore the massed-trained group did not react to spatial change 7 days post-habituation compared to the increased reactivity displayed by the spaced-trained group. Results are discussed in terms of poor encoding of the environment leading to poor retention.
Abstract: The substantial forward projection from hippocampal area CA1 to the subiculum has been comprehensively described, both anatomically and neurophysiologically. There are few data, however, regarding the existence of a backward projection from the subiculum to area CA1. We present here new electrophysiological evidence for the existence of this projection. We demonstrate a positive-going deflection in the evoked synaptic response in area CA1 following stimulation in dorsal subiculum. We also found a small, but significant, paired-pulse facilitatory effect at a 100-ms interstimulus interval. We were unable to induce long-term potentiation following high-frequency stimulation, but were able to induce short-term potentiation.
Abstract: Lipopolysaccharide is derived from the cell wall of gram-negative bacteria and is a potent endotoxin which causes the release of cytokines in the CNS. We examined the effect of lipopolysaccharide on synaptic transmission and synaptic plasticity in the hippocampal area CA1-subicular pathway in vivo. We found that lipopolysaccharide did not affect baseline synaptic transmission in this pathway; it did, however, reduce the magnitude of paired-pulse facilitation, a form of short-term plasticity thought to be primarily presynaptic in origin. We then examined the interaction between lipopolysaccharide and two common models for the biological basis of memory: high-frequency stimulation induced long-term potentiation and low-frequency stimulation induced long-term depression of synaptic transmission. We found that lipopolysaccharide blocked long-term potentiation following high-frequency stimulation and also induced potentiation of synaptic transmission after low-frequency stimulation. Lipolysaccharide blocked paired-pulse facilitation selectively at short rather than longer interstimulus intervals. Thus, lipopolysaccharide has different effects on synaptic transmission in this pathway depending on the frequency and length of stimulation. These results provide new insights into the action of lipopolysaccharide on various forms of plasticity in the hippocampus, an area known to play a vital role in learning and memory.
Abstract: We investigated the effects of a single injection and a daily injection of lipopolysaccharide (LPS) on spatial learning and brain-derived neurotrophic factor (BDNF) expression in the rat dentate gyrus. LPS is derived from the cell wall of Gram-negative bacteria and is a potent endotoxin that causes the release of cytokines such as interleukin-1 and tumour necrosis factor. LPS is thought to activate both the neuroimmune and neuroendocrine systems; it also blocks long-term potentiation in the hippocampus. Here, we examined the effects of LPS on a form of hippocampal-dependent learning-spatial learning in the water maze. Rats were injected with LPS intraperitoneally (100 microg/kg) and trained in the water maze. The first group of rats were injected on day 1 of training, 4 h prior to learning the water maze task. Groups 2 and 3 were injected daily, again 4 h prior to the water-maze task; group 2 with LPS and group 3 with saline. A number of behavioural variables were recorded by a computerised tracking system for each trial. The behavioural results showed a single injection of LPS (group 1) impaired escape latency in both the acquisition and retention phases of the study, whereas a daily injection of LPS did not significantly impair acquisition or retention. BDNF expression was analysed in the dentate gyrus of all animals. No significant differences in BDNF expression were found between the three groups.
Abstract: We review the neuroanatomical, neurophysiological and functional properties of the mammalian subiculum in this paper. The subiculum is a pivotal structure positioned between the hippocampus proper and entorhinal and other cortices, as well as a range of subcortical structures. It is an under-investigated region that plays a key role in the mediation of hippocampal-cortical interaction. We argue that on neuroanatomical, physiological and functional grounds, the subiculum is properly part of the hippocampal formation, given its pivotal role in the hippocampal circuit. We suggest that the term "subicular complex" embraces a heterogenous range of distinct structures and this phrase does not connote a functionally or anatomically meaningful grouping of structures. The subiculum has a range of electrophysiological and functional properties which are quite distinct from its input areas; given the widespread set of cortical and subcortical areas with which it interacts, it is able to influence activity in quite disparate brain regions. The rules which govern the plasticity of synaptic transmission are not well-specified; it shares some properties in common with the hippocampus proper, but behaves quite differently in other respects. Equally, its functional properties are not well-understood, it plays an important but ill-defined role both in spatial navigation and in mnemonic processing. The important challenges for the future revolve around the theoretical specification of its unique contribution to hippocampal formation processing on the one hand, and the experimental investigation of the many open questions (anatomical, physiological, pharmacological, functional) regarding its properties, on the other.
Abstract: This paper reviews investigations of synaptic plasticity in the major, and underexplored, pathway from hippocampal area CA1 to the subiculum. This brain area is the major synaptic relay for the majority of hippocampal area CA1 neurons, making the subiculum the last relay of the hippocampal formation prior to the cortex. The subiculum thus has a very major role in mediating hippocampal-cortical interactions. We demonstrate that the projection from hippocampal area CA1 to the subiculum sustains plasticity on a number of levels. We show that this pathway is capable of undergoing both long-term potentiation (LTP) and paired-pulse facilitation (PPF, a short-term plastic effect). Although we failed to induce long-term depression (LTD) of this pathway with low-frequency stimulation (LFS) and two-pulse stimulation (TPS), both protocols can induce a "late-developing" potentiation of synaptic transmission. We further demonstrate that baseline synaptic transmission can be dissociated from paired-pulse stimulation of the same pathway; we also show that it is possible, using appropriate protocols, to change PPF to paired-pulse depression, thus revealing subtle and previously undescribed mechanisms which regulate short-term synaptic plasticity. Finally, we successfully recorded from individual subicular units in the freely-moving animal, and provide a description of the characteristics of such neurons in a pellet-chasing task. We discuss the implications of these findings in relation to theories of the biological consolidation of memory.
Abstract: The downregulation of synaptic efficacy is referred to as long-term depression (LTD). Recent work has shown that a two-pulse stimulation (TPS) protocol is successful at inducing LTD in vivo in area CA1 of the hippocampus. Here, we examine the ability of two TPS protocols and two low-frequency stimulation (LFS) protocols to induce LTD in the projection from hippocampal area CA1 to the subiculum in the anaesthetized rat. We find no evidence of LTD induction with TPS or LFS protocols. Instead, with three of the protocols (both TPS protocols and 1 Hz LFS), a late-developing potentiation is observed.
Abstract: The navigational abilities of rats were examined using the water maze after disorientation induced by rotation and/or swimming in darkness. Control and light-disoriented groups performed similarly, whereas the dark group and the dark-disoriented groups were initially much slower but improved to control levels. After receiving bilateral parietal lesions, multiple start position tests showed that both rotation groups were severely impaired in finding the hidden platform. The effects of disorientation induced by darkness and by rotation are therefore separable.
Abstract: Long-term potentiation (LTP) is a popular model for the synaptic changes that may occur during learning and memory; it involves a strengthening of synaptic response and is readily induced in the hippocampus, an area of the brain implicated in learning and memory. Previous research on LTP has focused on 'early' components of the hippocampal circuitry, that is, the dentate gyrus and areas CA1 and CA3. This paper examines the plasticity of the CA1-subiculum pathway; we extend our previous work in this area demonstrating that the projection from area CA1 to subiculum sustains theta-patterned stimulus-induced LTP in vivo. We show that this pathway remains potentiated over a long period (3 h). Furthermore, once this projection is potentiated, it seems resistant to further episodes of high-frequency stimulation. We discuss the implications of these findings for theories of hippocampal-cortical interaction during the biological consolidation of memory.
Abstract: Long-term potentiation (LTP) is a popular model of the synaptic plasticity which may be engaged by the biological processes underlying learning and memory. Most available studies of LTP have concentrated on the analysis of LTP occurring in 'early' components of the hippocampal circuit (for example, dentate gyrus and area CA1). We examine here, for the first time, LTP as it occurs in the massive, unidirectional projection from CA1 to the subiculum in vivo. We show that this projection sustains high-frequency stimulus-induced LTP (10 trains of 20 stimuli at 200 Hz; intertrain interval 2 s; LTP 181 +/- 9% at 30 min post-LTP induction). In addition, input-output (I/O) curves show a leftward shift for all stimulation values.
Abstract: Studies of the interaction between long-term potentiation (LTP) and paired-pulse facilitation (PPF) may throw light on the role of presynaptic factors in LTP. We examine here, for the first time, the nature of PPF in the CA1-subiculum projection. PPF peaks at a 50 ms interstimulus interval (ISI) and is evident at ISIs from 10 to 500 ms. There is no PPF effect at a 1000 ms ISI. PPF decreases in magnitude post-LTP induction across the middle range of ISI values tested (30, 50 and 100 ms). There is a positive correlation between initial PPF values and LTP; this correlation increases as the ISI increases. Initial values and the change in PPF post-LTP are also negatively correlated.
