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Introduction: The neuropeptide Y (NPY) is broadly distributed in the central nervous system (CNS), and it has been related to neuroprotective functions. NPY seems to be an important component to counteract brain damage and cognitive impairment mediated by drugs of abuse and neurodegenerative diseases, and both NPY and its Y 2 receptor (Y 2 R) are highly expressed in the hippocampus, critical for learning and memory. We have recently demonstrated its influence on cognitive functions; however, the specific mechanism and involved brain regions where NPY modulates spatial memory by acting on Y 2 R remain unclear., Methods: Here, we examined the involvement of the hippocampal NPY Y 2 R in spatial memory and associated changes in brain metabolism by bilateral administration of the selective antagonist BIIE0246 into the rat dorsal hippocampus. To further evaluate the relationship between memory functions and neuronal activity, we analysed the regional expression of the mitochondrial enzyme cytochrome c oxidase (CCO) as an index of oxidative metabolic capacity in limbic and non-limbic brain regions., Results: The acute blockade of NPY Y 2 R significantly improved spatial memory recall in rats trained in the Morris water maze that matched metabolic activity changes in spatial memory processing regions. Specifically, CCO activity changes were found in the dentate gyrus of the dorsal hippocampus and CA1 subfield of the ventral hippocampus, the infralimbic region of the PFC and the mammillary bodies., Conclusions: These findings suggest that the NPY hippocampal system, through its Y 2 R receptor, influences spatial memory recall (retrieval) and exerts control over patterns of brain activation that are relevant for associative learning, probably mediated by Y 2 R modulation of long-term potentiation and long-term depression., (Copyright © 2021. Published by Elsevier Inc.)

Mitochondrial dysfunction plays a central role in hepatic encephalopathy (HE), due to changes in enzyme cytochrome c-oxidase (CCO), causing a decline in brain metabolism. We used an HE animal model and applied intracranial administration of methylene blue (MB) and transcranial photobiomodulation (PBM), both targeting CCO, to determine their differential effects on recovering cognition. Five groups of rats were used: sham-operated group + saline (SHAM + SAL, n = 6), hepatic encephalopathy + SAL (HE + SAL, n = 7), SHAM + methylene blue (SHAM + MB, n = 7), HE + MB (n = 7), HE + PBM (n = 7). PBM animals were exposed transcranially to 670 +/- 10 nm LED light at a dose of 9 J/cm 2 once a day for 7 days, and the MB and SAL groups were injected with 2.2 μg/0.5 μL in the accumbens. Cognitive dysfunction was evaluated on a striatal stimulus-response task using the Morris water maze. Our results showed cognitive improvement in the HE group when treated with MB. This improvement was accompanied by a decrease in CCO activity in the prefrontal cortex, dorsal striatum, and dorsal hippocampus. When comparing MB and PBM, we found that, although both treatments effectively improved the HE-memory deficit, there was a differential effect on CCO. A general decrease in CCO activity was found in the prefrontal and entorhinal cortices, dorsal striatum, and hippocampus when PBM, compared to MB, was applied. Our results suggest that mitochondrial dysfunction and brain metabolic decline in HE might involve CCO alteration and can be improved by administering MB and PBM., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Memory involves a complex network system of interconnected brain areas in which labile trace memories are transformed into enduring ones and reorganized in a time-dependant manner. Although it has been observed that remote memories are less prone to destabilizing, they can become fragile and lead to behavioural decline. We explored the behavioural outcomes of male and female rats in response to the reactivation of a previously acquired allocentric spatial reference memory, under conditions in which animals have shown a retrieval decay. In addition, we assessed their brain metabolic activity through cytochrome c oxidase (CCO) histochemistry. Our results show that a spatial memory amnesia-like behaviour with a time interval of 45 days can be recovered after re-exposure to the environmental configuration with the reinforced contingencies. Moreover, we observed that, following reactivation, male rats reveal a decrease in metabolic activity in septal nuclei and thalamic structures, whereas female rats add a metabolic reduction in the hippocampus, amygdala, mPFC, and retrosplenial, parietal and rhinal cortices, suggesting that they efficiently employ these brain areas when reactivation a memory that has suffered a decay with time. Finally, although male and female rats perform the behavioural task equally, we found sex differences at the brain metabolism level, revealing the differential contribution of brain limbic system energy demands by sex, even when their performance is similar. In conclusion, our work provides behavioural and brain data about remote spatial retrieval and memory reactivation processes., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Neuropeptide Y (NPY) is highly abundant in the brain and is released as a co-transmitter with plasticity-related neurotransmitters such as glutamate, GABA and noradrenaline. Functionally, its release is associated with appetite, anxiety, and stress regulation. NPY acting on Y2 receptors (Y 2 R), facilitates fear extinction, suggesting a role in associative memory. Here, we explored to what extent NPY action at Y 2 R contributes to hippocampus-dependent spatial memory and found that dorsal intrahippocampal receptor antagonism improved spatial reference memory acquired in a water maze in rats, without affecting anxiety levels, or spontaneous motor activity. Water maze training resulted in an increase of Y 2 R, but not Y 1 R expression in the hippocampus. By contrast, in the prefrontal cortex there was a decrease in Y 2 R, and an increase of Y 1 R expression. Our results indicate that neuropeptide Y 2 R are significantly involved in hippocampus-dependent spatial memory and that receptor expression is dynamically regulated by this learning experience. Effects are consistent with a metaplastic contribution of NPY receptors to cumulative spatial learning., (Copyright © 2020. Published by Elsevier B.V.)

The teleost fish hippocampal pallium, like the hippocampus of tetrapods, is essential for relational map-like spatial memories. In mammals, these relational memories involve the dynamic interactions among different hippocampal subregions and between the hippocampus-neocortex network, which performs specialized operations such as memory encoding and retrieval. However, how the teleost hippocampal homologue operates to achieve comparably sophisticated spatial cognition capabilities is largely unknown. In the present study, the progressive changes in the metabolic activity of the pallial regions that have been proposed as possible homologues of the mammalian hippocampus were monitored in goldfish. Quantitative cytochrome oxidase histochemistry was used to measure the level of activation along the rostrocaudal axis of the ventral (Dlv) and dorsal parts of the dorsolateral division (Dld) and in the dorsoposterior division (Dp) of the goldfish telencephalic pallium throughout the time course of the learning process of a spatial memory task. The results revealed a significant increase in spatial memory-related metabolic activity in the Dlv, but not in the Dld, suggesting that the Dlv, but not the Dld, is comparable to the amniote hippocampus. Regarding the Dlv, the level of activation of the precommissural Dlv significantly increased at training onset but progressively declined to finally return to the basal pretraining level when the animals mastered the spatial task. In contrast, the commissural Dlv activation persisted even when the acquisition phase was completed and the animal's performance reached an asymptotic level. These results suggest that, like the dentate gyrus of mammals, the goldfish precommissural Dlv seems to respond nonlinearly to increments of change in sensory input, performing pattern separation under highly dissimilar input patterns. In addition, like the CA3 of mammals, the commissural Dlv likely operates in a continuum between two modes, a pattern separation or storage operation mode at early acquisition when the change in the sensory input is high, probably driven by the precommissural Dlv output, and a pattern completion or recall operation mode when the animals have mastered the task and the change in sensory input is small. Finally, an unexpected result of the present study is the persistent activation of the area Dp throughout the complete spatial task training period, which suggests that the Dp could be an important component of the pallial network involved in spatial memory in goldfish, and supports the hypothesis proposing that the Dp is a specialized part of the hippocampal pallium network., (© 2017 S. Karger AG, Basel.)

Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The importance context has been broadly studied in the management of phobias and in the drug addiction literature. The way in which changes to a context influence behavior after the simple acquisition of a passive avoidance task remains unclear. The hippocampus has long been implicated in the contextual and spatial processing required for contextual fear, but its role in encoding the aversive component of a contextual fear memory is still inconclusive. Our work tries to elucidate whether a change in context, represented as differences in the load of the stimuli, is critical for learning about the context-shock association and whether this manipulation of the context could be linked to any change in metabolic brain activity requirements. For this purpose, we used an avoidance conditioning task. Animals were divided into three different experimental conditions. In one group, acquisition was performed in an enriched stimuli environment and retention was performed in a typically lit chamber (the PA-ACQ-CONTX group). In another group, acquisition was performed in the typically lit chamber and retention was undertaken in the highly enriched chamber (the PA-RET-CONTX group). Finally, for the control group, PA-CN-CONTX, acquisition, and retention were performed in the enriched stimuli environment. Our results showed that the PA-ACQ-CONTX group had longer escape latencies and poorer retention than the PA-RET-CONTX and PA-CN-CONTX groups after 24 h of acquisition under contextual changes. To study metabolic brain activity, histochemical labelling of cytochrome c-oxidase (CO) was performed. CO results suggested a neural circuit including the hippocampus, amygdala, thalamus, parahippocampal cortices, and mammillary nuclei that is involved in the learning and memory processes that enable context-dependent behavior. These results highlight how dysfunction in this network may be involved in the contextualization of fear associations that underlie several forms of psychopathology, including post-traumatic stress disorder, schizophrenia, and substance abuse disorders., (© 2015 Wiley Periodicals, Inc.)

Contextual memory implies recognition based on the association between past and present events experienced. It is important for daily functioning and dysfunctional in many neuropsychological disturbances. The network related to this memory is still open for debate, even though it has been associated with medial temporal lobe regions, including the perirhinal, entorhinal and temporal association cortices, as well as the hippocampus and prefrontal cortex. Our work tries to elucidate whether a change in the context, such as differences in the amount of stimuli presented on the walls and floor of an open field during object exploration, affects the recognition of an object that has been experienced before, and whether this context manipulation could be linked to changes in c-Fos expression. For this purpose, we used a one-trial novel-object recognition task. The animals were divided into two different experimental conditions; in the OR-NORMAL group, the sample and probe test were performed in the same context. However, in the OR-CONTEXT group, the probe test was performed in a different context. Our results showed that the OR-NORMAL group presented a greater exploration of objects than the OR-CONTEXT group. However, both groups presented significant exploration of the novel object. To label the brain regions involved in novel-object recognition under these conditions, we marked the expression of c-Fos protein. Results suggest that a neural circuit that includes the hippocampus, entorhinal and temporal association cortices is involved in the recognition of the novel-object in a novel context., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The hippocampus has been established as a site of plasticity during the acquisition of spatial memory. The memory for spatial locations is impaired in patients who develop hepatic encephalopathy (HE). We wondered how the hippocampus can manage different hippocampal-dependent tasks in a type B model of the early evolutive phases of HE induced by triple portal vein ligation. We used a one-trial object-place recognition task that involves making judgements about whether a stimulus was encountered before in that location and a reversal learning task performed in the Morris water maze that involves reward-guided behavior and decision making. Our behavioral results showed impairments in the acquisition of both tasks by the portal hypertension group compared with the sham-operated group. To label brain areas related to these tasks, we marked the expression of the c-Fos protein and revealed high c-Fos immunoreactivity in cornu ammonis 1 (CA1), cornu ammonis 3 (CA3) and entorhinal (Ent) cortex of the PH group compared with the SHAM group in the object-place recognition task and a decrease in c-Fos-positive cells in the reversal task in the CA1, CA3, dentate gyrus (DG), cingulate (CG), prelimbic (PL), and infralimbic (IL) cortices in the PH group compared with the SHAM group. In conclusion, the study corroborated the pivotal role of the hippocampus in spatial memory deficits found in the early stages of type B HE and noted its differential contribution in each of the tasks., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

We have studied the performance of a spatial reference memory task, the navigation strategy and the changes in the cytochrome c oxidase activity (COx) in different brain regions in exercised (forced exercise, 10 consecutive days, 15min/day) and non-exercised adult Wistar rats. The spatial learning task was carried out in the radial-arm water maze (RAWM) for four days with six daily trials, and on the fifth day, a probe session was run, in which we rotated the position of the distal cues 90° in a clockwise direction. During the four days of training, the exercised group showed shorter latency and distance traveled to find the platform, as well as fewer memory errors and reduced use of non-appropriate navigation strategies according to the protocol of the task (egocentric). Interestingly, the rotation of the cues did not affect the performance of the exercised group, in contrast to the non-exercised group, which spent more time in the center of the maze and traveled longer distance to find the platform. Finally, higher COx activity in the cingulate and the retrosplenial cortices, as well as in the dorsal CA1 and CA3 was found in the exercised group. All in all, it seems that the exercise favored the configuration of an efficient and accurate cognitive map of the environment, which was supported by our finding that the rotation of the cues, without altering their overall configuration, did not affect performance. The brain regions with higher COx activity in the exercised group seem to be involved in this function., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Our aim was to assess the changes in the Synapsin I and glucocorticoid receptor (GR) expression induced by behavioral testing in the dorsal and ventral hippocampi of standard and enriched aged Wistar rats. The environmental enrichment (EE) was carried out 3h/day over a period of two months and then, the rats were tested in the elevated zero-maze (EZM) and radial-arm water maze (RAWM). Behavioral results showed that, even at an advanced age, EE was able to reduce anxiety-related behaviors and improve the performance in the RAWM. Regarding the neurobiological data, Synapsin I expression in the dorsal CA3, but not in the ventral, was enhanced both in enriched and standard rats when they performed the behavioral testing. Interestingly, the EE exposure was enough to increase Synapsin I in the ventral CA3. The analysis of GR in the dorsal hippocampus showed an increase of this receptor in the dDG both in enriched and standard rats when they performed the behavioral testing, whereas in the dCA1 and dCA3, the effect of the testing depended on the previous housing condition. In the ventral region, we found that the effects of EE were higher because on the one hand, the GR expression induced by the behavioral testing was enhanced in the dSUB, vCA1 and vCA3 when the rats were previously enriched and on the other hand, EE, regardless of the behavioral testing, increased the GR expression in the vDG and vSUB. Therefore, our results suggest that the effect of the behavioral testing on the neurobiological mechanisms studied is different depending on the previous housing condition of aged rats., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Environmental enrichment (EE) produces a remarkable degree of structural and functional plasticity in the hippocampus and possible mediators of these changes, such as glucocorticoid receptors (GRs), are of considerable interest. GRs are richly expressed in the hippocampus and they are involved in the adaptation to stressors and facilitate active coping in anxious situations. In this study, we assessed the effect of an EE protocol (24h/day during 69days) in adult Wistar rats on the activity in the elevated-zero maze (EZM), performance in the holeboard task (HB) and we also examined the changes in the glucocorticoid receptors (GRs) expression in the dorsal hippocampus (CA1, CA3 and DG). Our EE protocol reduced anxious behaviors in the EZM, so the animals spent more time and made more entries into the open sections. In the HB task, the enriched group showed more explorative behavior, a reduction of anxiety-related behaviors and a better cognitive performance compared to non-enriched animals. With regard to the GR expression, the EE condition produced an increase in the number of immunopositive cells for GRs in CA1, CA3 and DG. These results suggest that the better performance of enriched animals could be mediated in part by the increase of GRs in the dorsal hippocampus, which may alter the hippocampal neuronal function and accordingly, the anxiety levels, the spatial memory performance and the exploration levels in these animals., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions.

The hippocampus and the striatum have traditionally been considered as part of different and independent memory systems. However, there is evidence that supports a functional interaction between the hippocampus and the dorsal striatum at least in particular learning tasks. Here, we evaluated the functional contribution of both brain regions in a visual discrimination learning task using cytochrome c oxidase (CO) quantitative histochemistry. Compared with other brain metabolic mapping techniques, CO activity reflects steady-state neuronal energy demand. Rats were trained for 6 days in a water T-maze to find a hidden escape platform associated with an intramaze visual cue. A control group of animals swam for an equivalent amount of time compared as the trained group but without any escape platform available. After finishing the behavioral task, CO activity was measured in subdivisions of the dorsal hippocampus and the dorsal striatum in both groups. Results show significantly higher CO activity in the CA1 area and the dentate gyrus of the dorsal hippocampus in the trained rats compared with the control group. In addition, a significant negative functional cross-correlation between area CA1 of the dorsal hippocampus and the anterodorsal striatum was found. Our results support current theories on competitive interaction of different memory systems during visual discrimination learning., (Copyright © 2011 Wiley Periodicals, Inc.)

The hippocampus is probably the most studied brain structure regarding memory. Each brain hemisphere contains one hippocampus, and subjects with unilateral hippocampal lesions can perform adequately in several behavioral tasks. This property allows studying how both hippocampi interact. In this work, we show that the information acquired in a passive avoidance task with one hippocampus can be retrieved and used by the brain when the hippocampal side involved in the acquisition is blocked with TTX. The pre-exposition to the context is decisive. By combining behavioral tasks and cytochrome oxidase histochemistry we demonstrated that several brain structures, including the hippocampus, amygdala and other related regions, change their activity under the above-mentioned treatments., (Copyright © 2010 Wiley-Liss, Inc.)

The oxidative metabolism was assessed in the hippocampus and related regions in rats that were trained in a spatial short-term memory task in the water maze following distinct training schedules. The cytochrome oxidase (COx) histochemistry was evaluated in groups of rats that received a daily session made up of either two or three learning trials. An untreated group was added to determine baseline levels of COx. We found that the 3-Trials group exhibited a better performance concerning the differences in latency between trials 1 and 2. Trained groups showed higher COx activity than the untreated group in the medial prefrontal cortex, dentate gyrus, CA1, and the mammillary region. However, a decrease in COx activity was found in the dentate gyrus, CA1, and supramammillary region of the 3-Trials group. In addition, COx activity levels found in this group were similar to those of the untreated group in some thalamic nuclei. Most of the regions that presented significant correlations between COx activity and behavioral scores were found in the 3-Trials group. These findings suggest an influence of task difficulty in the oxidative metabolism of brain regions involved in spatial learning., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Patients with liver dysfunction often suffer from hepatic encephalopathy (HE), a neurological complication that affects attention and memory. Various experimental animal models have been used to study HE, the most frequently used being the portocaval shunt (PCS). In order to determine brain substrates of cognitive impairment in this model, we assessed reversal learning and c-Fos expression in a rat model of portosystemic derivation. PCS and sham-operated rats (SHAM) were tested for reversal learning. Brains were processed for c-Fos immunocytochemistry. The total number of c-Fos positive nuclei was quantified in the prefrontal cortex and hippocampus. The spatial reference memory task showed no differences between groups in escape latencies. The no-platform probe test showed that both the PCS and the SHAM learned the location of platform. However, the PCS group perseverated in the old target during reversal. The PCS group presented less c-Fos- positive cells in prelimbic cortex, CA1 and dentate gyrus of the dorsal hippocampus than SHAM. Overall, these results suggest that this specific model of portosystemic hepatic encephalopathy produces reversal learning impairment that could be linked to dysfunction in neuronal activity in the prefrontal cortex and hippocampus.

The oxidative metabolism was assessed in the septal, intermediate and temporal hippocampus in Wistar rats that were trained following a working memory schedule in the Morris water maze. The cytochrome oxidase histochemistry was measured at 90 min, 6, 24 and 48 h post-training. We found an increase in the septal dentate gyrus at 90 min, at 6h the increase was also found in CA3 and CA1 regions and returned to basal levels at 24h. In contrast, the intermediate region showed lower increase, limited to the dentate gyrus and CA3 at 24h post-training. No changes were found in the temporal hippocampus. These findings suggest that septal and intermediate hippocampal zones participate in this spatial learning and contribute at different moments to process this information.

Hepatic encephalopathy (HE) is a frequent neurological complication observed in patients with liver malfunction. Previous studies have shown memory impairment in these patients. In order to investigate brain substrates of spatial working memory impairment in chronic HE, neuronal expression of c-Fos protein was studied in an experimental model of cirrhosis. Control and cirrhotic rats were trained on a spatial working memory task in the Morris water maze (MWM). Differences between groups were found in the working memory task. Cirrhotic rats were unable to locate the platform in the retention trial. Neuronal activation, measured by c-Fos protein, was compared between groups. No differences were found in c-Fos expression of control and cirrhotic rats that were not tested in the MWM. Working memory task produced increase in c-Fos positive cells in dorsal hippocampus, CA1 and CA3, and prefrontal cortex in control group compared to thioacetamide group or naïve, which only swam in the maze during a similar time. These findings suggest that cirrhotic rats show spatial working memory impairment that could be linked to dysfunction in neuronal activity in prefrontal cortex and hippocampus.

This study was aimed to determine the effect of unilateral hippocampal inactivation on spatial memory retrieval in male and female Wistar rats. Subjects were chronically implanted with a stainless-steel cannula that enabled unilateral intrahippocampal injections of tetrodotoxin, a sodium channel blocker. Rats were trained during eight consecutive days on the Morris water maze task. On day 1, subjects received a visible platform session. From day 2 to day 7 the hidden platform was located in North quadrant and on day 8 the hidden platform changed to the opposite location. Subjects were randomly distributed into four groups: male saline, male TTX, female saline, female TTX. Saline or TTX was applied 30min before training but only on days 7 and 8. Results showed that males outperform females during the initial training (days 2-6). After TTX injection, both male and female rats were impaired. However, a detailed analysis revealed that the impairment in females was more pronounced, both during the retrieval session (day 7) as well as during reversal (day 8). This data points to a different role of the hippocampus or a different distribution of memories in both sexes.

Consolidation processes were studied in the rat by using functional inactivation techniques. Previous results showed that unilateral hippocampal inactivation alters consolidation. It is not clear if bilateral treatments increase the impairment. Wistar rats were trained in the Morris water maze during 4 consecutive days. Subjects received saline or tetrodotoxin in the dorsal hippocampus 1 min after training. Results showed that bilateral as well as unilateral treatments impair consolidation to the same degree, as shown by the mean latency to reach the platform. In both cases, the impairment is only visible in the first trial of the session following the blockade.

The aim of the present study was to provide further evidence on the role of particular subdivisions of the mammillary bodies, anterior thalamus and dorsal hippocampus to contextual and auditory fear conditioning. We used c-Fos expression as a marker of neuronal activation to compare rats that received tone-footshock pairings in a distinctive context (conditioned group) to rats being exposed to both the context and the auditory CS without receiving footshocks (unconditioned group), and naïve rats that were only handled. Fos immunoreactivity was significantly increased only in the anterodorsal thalamic nucleus and the lateral mammillary nucleus of the conditioned group. However, the dorsal hippocampus showed the highest density of c-Fos positive nuclei in the naïve group as compared to the other groups. Together, our data support previous studies indicating a particular involvement of the mammillary bodies and anterior thalamus in fear conditioning.

Understanding hippocampal participation in memory processes is one of the goals in neuroscience research. By blocking the hippocampus unilaterally in Wistar rats, we assessed the contribution of this brain structure to memory in a passive avoidance task. Subjects were distributed into four groups. Group 1 received tetrodotoxin (TTX) in the right hippocampus during acquisition and retrieval phases. Group 2 had the same procedure as group 1, except that the contralateral hippocampus was blocked during retrieval. Subjects from group 3 acquired the task with saline (both hippocampi intact) and retrieved with the right hippocampus inactivated. Finally, group 4 received TTX unilaterally 2 min after acquisition to determine the hippocampal role in consolidation. Results showed that group 2 was impaired, compared with the other groups, during retrieval. These findings reveal that the hippocampal contribution to this task differs from that in other tasks considered to be hippocampus dependent., ((c) 2007 Wiley-Liss, Inc.)

Hippocampal and striatal systems are widely related to spatial tasks. Depending on the strategies used, different memory systems can be activated. In this study, the authors used the cytochrome c-oxidase technique as a functional marker of the hippocampal and dorsal striatum activity related to training in several water maze tasks. Current results show a differential participation of the hippocampal and striatal systems in navigation. When spatial information is relevant, participation of the hippocampal system is more important, and when the task is similar to a response learning one, the striatal system is more active. According to computational models, CA3 seems to be more active when the associative demand is higher, whereas CA1 and dentate gyrus activity are higher when spatial information processing is required., (Copyright 2006 APA, all rights reserved.)

Long-term memories seem to require protein synthesis to be established. This process can be related with synaptogenesis resulting in changes in the form or even in the number or proportion of synaptic contacts. Results from behavioral studies assessing quantitative changes associated with different learning tasks are controversial. The aim of our work was to assess whether the number of CA1 hippocampal synaptic contacts can be modified after training in different tasks in the Morris water maze (MWM). We found transient changes in the synaptic density of the symmetric synapses associated with place learning. A reduced synaptic density of the symmetric synapses in the stratum radiatum of CA1 was found at 48 h posttraining, returning to control levels 72 h posttraining. The same effect was observed 1 h after training in a nonspatial task. Synaptic changes found in the CA1 shortly after water maze training suggest a possible participation of the hippocampus in the acquisition of nonspatial tasks together with a role in the short-term consolidation of spatial memory. As no changes were found in the total number of synapses counted, it is likely that subtle changes in synaptic efficacy than new synapse generation may be sufficient to support the acquisition and maintenance of new memories., ((c) 2005 Wiley-Liss, Inc.)

The hippocampus is one of the more widely studied structures related with spatial memory. In this study, we assessed the effect of unilateral inactivation of the dorsal hippocampus with tetrodotoxin (TTX) on the performance displayed by Wistar rats in the spatial version of the Morris water maze. In experiment 1, we injected into the dorsal hippocampus in two different groups of rats 1 microl of saline solution or 5 ng of TTX in 1 microl of saline each day immediately after the training during four consecutive days. This procedure blocked consolidation and impaired spatial memory in the TTX group. In experiment 2, a new group of subjects was trained in the Morris water maze for 8 days and was administered 1 microl of saline on day 7 (saline session) and TTX on day 8 (TTX session) into the dorsal hippocampus 40 min before the training. Only the treatment with TTX altered the retrieval of memories. These experiments showed that unilateral interventions on the dorsal hippocampus can affect consolidation as well as retrieval of well-established spatial memories.

It is known that expression of glial fibrillary acidic protein (GFAP) as an astrocyte-specific marker can be regulated by levels of circulating gonadal steroids during postnatal development. In addition, astrocytes play an important role in the physiology of the hippocampus, a brain region considered sexually dimorphic at the neuronal level in rodents. To evaluate the contribution of glial cells to gender-related differences in the hippocampus, we estimated the number of GFAP-immunoreactive (GFAP-IR) astrocytes in the hippocampus (CA1 and CA3 areas, dorsal and ventral regions) of male and female rats aged 30 days. Groups of 30-day-old masculinized females (TP-females; injected with testosterone propionate at birth) and feminized males (FLU-males, castrated and treated with flutamide, an androgen receptor antagonist) were included to assess the effects of gonadal hormones on these hippocampal astrocytes. Using the optical fractionator method, the total number of GFAP-IR cells found in CA1 and CA3 areas was significantly higher in males compared to that in age-matched females. This numerical pattern was reversed in TP-females and FLU-males in both hippocampal areas. In addition, more GFAP-IR cells were found in dorsal hippocampus than in the ventral region in the CA1 area from all experimental groups, whereas this result was found in the CA3 area from males and TP-females. Our results suggest an essential contribution of gonadal hormones to gender differences found in the astrocyte population of the rat hippocampus during development., (Copyright (c) 2004 Wiley-Liss, Inc.)

The effects of classical fear conditioning in different regions of the limbic system were analysed using cytochrome oxidase (CO) histochemistry. Wistar rats were submitted to different conditions. Rats in the group Paired received tone-shock pairing, to elicit conditioned suppression of lever pressing (i.e., tone will evoke conditioned fear responses). The group Unpaired underwent random presentations of these stimuli and developed no conditioned fear. Untrained animals were also included as a control group. A significant decrease in CO activity was found in the medial septal area and the dorsal hippocampus (CA3 subfield and dentate gyrus) in the group Paired as compared with the group Unpaired. Furthermore there was greater metabolic activity in the control group as compared with the other two groups. No differences in CO labelling of the basolateral amygdala were detected among all groups. These findings suggest that the septohippocampal system plays an important role in controlling conditioned fear behaviour.

We quantified the number of glial fibrillary acidic protein immunoreactive (GFAP-IR) astrocytes in the CA1 and CA3 areas of the adult rat hippocampus. The dorsal and ventral regions of the hippocampus were taken into account to estimate the GFAP-IR cells using unbiased stereological techniques. Males had a higher number of GFAP-IR astrocytes in the CA3 area, whereas females had more in the CA1 area. No sex difference was found between dorsal and ventral regions, although most GFAP-IR astrocytes were located in the dorsal hippocampus.

Chronic alcohol consumption induces morphological changes in the central nervous system and withdrawal does not reverse these changes. It is well known that the hippocampal formation is one of the brain regions most sensitive to prolonged alcohol ingestion. The aim of our study was to evaluate the transcriptional neuronal activity by measuring the argyrophilic nucleolar organizer regions (AgNORs) in the dentate gyrus, CA3, and CA1 hippocampal areas from adult male rats receiving chronic administration of ethanol (ALC) and after withdrawal (WDL). The parameters evaluated were the number and area of AgNORs, together with the area of nucleus and the proportion between AgNOR and nuclear areas (ratio). The animals from ALC and WDL groups showed a reduction in the number of AgNOR per cell as compared to the control group. CA3 was the hippocampal area most affected by chronic alcohol intake. No improvement was observed in animals after withdrawal. Our data support the idea that the chronic intake of alcohol decreases protein synthesis in hippocampal neurons at an early age. This decrease may explain the memory impairment showed by rats receiving chronic treatment with alcohol because, both in humans and rats, it is associated with a reduction in the number of cholinergic neurons in the basal forebrain that would in turn affect the hippocampal function.

Introduction: Since publication of the book The hippocampus as a cognitive map by O'Keefe and Nadel in 1978, several theoretical and experimental works have supported the participation of the hippocampus in rodents in spatial processing. Since then, great advances have been made into understanding the potential role of the hippocampus in learning and memory processes, relegating a secondary role to the hypothesis that, in rodents, the hippocampus is restricted to the formation of a cognitive map., Development: In this work, different forms of spatial navigation are analyzed (taxis, cartographic and route integration-based navigation) on a psychological and neurobiological level. The spatial function of the hippocampus proposed by O'Keefe and Nadel is discussed but a more general model is chosen that explains the function of the hippocampus in mammals, i.e. a model of relational memory. Therefore, in the context of relational memory we attempt to explain the different forms of spatial memory in rodents and present the most relevant experimental data that support a critical role for the hippocampus in this kind of memory., Conclusions: The studies reviewed in this work support an important role for the hippocampus in spatial processing. However, this does not appear to be its sole function and it possibly operates more widely also participating in relational memory.

Stereological methods (neuron and glial cell numbers) and histochemical methods (cytochrome c oxidase) were used to study postnatal development and aging of the CA1 and CA3 hippocampal areas in male rats. No changes were observed in 10 microns sections in the neuronal population of areas CA1 and CA3 in any of the groups (14 days, 21 days, adult-90 days and elderly-22 months). Statistical differences were found in the number of glial cells in both the CA1 and CA3 areas. An increase was observed in cytochrome oxidase (CO) activity in the CA1 area in the 14 day old rats compared to the other groups while in area CA3 this parameter increased in the 14 and 21 day old groups and the group of adult rats. No significant changes in CO activity were found in the elderly rats in both areas. These results are discussed in the light of those recorded in other areas of the limbic system.

The silver staining of the nucleolar organizer regions (Ag-NORs) was used in order to estimate the biosynthetic activity of three hippocampal areas (dentate gyrus, CA1 and CA3) during postnatal development and ageing. 32 Wistar rats were used and 4 groups were formed according to the age of the animals (14, 21, 90 days and 23 months). Several Ag-NOR parameters such as mean Ag-NOR area and the ratio between Ag-NOR and nuclear areas per neuronal cell were quantified using an image analysis system. High values of these parameters are associated with a high rate of rRNA transcription. In this way, the neural biosynthetic activity in all regions studied decreased as the older ages are reached. Differences between areas are shown with the dentate gyrus and CA1 areas decreasing faster. The different activity among these areas is discussed, taking into account the particular affect on these areas of some injuries and the ageing process. Our results support the hypothesis of NOR loss as a main cause of ageing as reported by other authors.

Early-life adversity impairs neuronal plasticity of the developing brain. In rodents, brain maturation processes, including neuro- and synaptogenesis, myelination, microglial maturation, and hypothalamic-pituitary-adrenal (HPA) axis development continue in the postnatal period. In our study, two models of early-life stress were used: repeated maternal separation (MS) from postnatal day (PND) 2 to PND14 for 3 h daily and single maternal deprivation (MD) on PND9 for 24 h. Effects of each type of early-life stress on neuron density, neurogenesis, microglial morphology, and HPA axis programming were studied in 15-day-old male mice. Neither early-life stress paradigm affected the expression of stress-related genes (Crh, Avp, Crhr1, Crhr2, Nr3c1, and Nr3c2) and the serum level of corticosterone on PND15. Immunohistochemical analysis was performed on slices of the hippocampus and prefrontal cortex (PFC) with antibodies against a marker of mature neurons (NeuN), of microglia (Iba1), proliferating cells (Ki67), and immature neurons (DCX). We found higher density of ameboid microglia and intermediate microglia in the PFC in groups MS and MD, respectively, than in a control group. In both stressed groups, a higher number of Ki67-positive cells was noted in the dentate gyrus. Thus, in mice, the process of transformation of ameboid microglia into ramified ones as well as a neurogenesis reduction take place during the second postnatal week, whereas early-life stress can disturb these processes in a stress- and region-dependent manner.

The Maier 3-table task comprises three phases conducted each day. During the exploration phase, rats explore the entire apparatus. During the information phase, the rats are placed on one of the three tables where food is found. During the test phase, the animals are placed at the starting point on one of the two remaining tables and must enter the goal table where they previously ate. The acquisition of the Maier 3-table task was slowed down after lesions of the septum, fornix, hippocampus, medial prefrontal cortex, or posterior parietal cortex. Because of its time-consuming nature, the Maier 3-table task has more recently been superseded by appetitive matching-to-place in Y- or T-mazes or the circular water maze, because experimenters skip over the exploration phase. Nevertheless, like the Maier 3-table task, the acquisition of the Y- or T-maze matching-to-place task was retarded after lesions of the medial septum or medial prefrontal cortex, more particularly its prelimbic-infralimbic part. Like the previous task, the water-maze version is sensitive to lesions of the medial septum or retrosplenial cortex. Despite methodological differences between the three procedures, these results indicate common neurobiological bases of matching-to-place learning. [ABSTRACT FROM AUTHOR]

Brain networks involved in working and spatial memory are closely intertwined, outlining a potential relation between these processes, which are also affected in non-pathological aging. Working memory is a pre-requisite for other complex cognitive processes. The main aim of this study is to explore how working memory capacity (WMC) can influence the asymmetrical decline in spatial orientation strategies in an older segment of population compared to young participants. Forty-eight older adults and twelve young students took part in the study. Working memory and spatial memory were assessed using the Change Localization Task and The Boxes Room Task, respectively. In The Boxes Room Task, two different configurations assessed the use of egocentric and allocentric reference frames. Results showed that older adults with better WMC outperformed those with lower WMC in several tasks. Independently of WMC capacity, older participants performed better in the allocentric condition of The Boxes Room. In addition, young participants outscored low WMC older participants, but did not differ from high WMC older adults. Overly, these findings support the important relationship between working memory capacity and spatial orientations abilities. Thus, basic cognitive mechanisms engaged in information processing could inform about other brain processes more complex in nature, like spatial orientation skills. [ABSTRACT FROM AUTHOR]

Environmental enrichment (EE) is an environmental paradigm encompassing sensory, cognitive, and physical stimulation at a heightened level. Previous studies have reported the beneficial effects of EE in the brain, particularly in the hippocampus. EE improves cognitive function as well as ameliorates depressive and anxiety-like behaviors, making it a potentially effective neuroprotective strategy against neurodegenerative diseases such as Alzheimer's disease (AD). Here, we summarize the current evidence for EE as a neuroprotective strategy as well as the potential molecular pathways that can explain the effects of EE from a biochemical perspective using animal models. The effectiveness of EE in enhancing brain activity against neurodegeneration is explored with a view to differences present in early and late life EE exposure, with its potential application in human being discussed. We discuss EE as one of the non pharmacological approaches in preventing or delaying the onset of AD for future research. [ABSTRACT FROM AUTHOR]

Depression is a leading cause of disability which at its worst leads to suicide. Its treatment relies on psychotherapy in combination with certain antidepressants (AD(s)) from various classes such as tricyclics, selective serotonin reuptake inhibitors, or serotonin and norepinephrine reuptake inhibitors (SNRIs). Among SNRIs, venlafaxine (VEN) is one such most commonly prescribed AD which is recently reported to be in the top 50 most prescribed drugs in the USA. Depression during pregnancy is a common condition, where prescribing an AD becomes necessary as untreated depression during pregnancy has its own complications for both mother and the child. This, probably, is why an incredible rise has been reported in prescribing ADs like VEN to pregnant women in the recent past, despite some studies, including the one from our own group, having reported the in-utero VEN-induced apoptotic neurodegeneration in the fetal neocortex and the consequent neurobehavioral anomalies in adulthood. However, there still exists a lack of insight into the effects of intrauterine exposures of VEN on other fetal brain regions like the hippocampus (HPC) and striatum (STR) and the consequent effects on their cognitive and emotional wellbeing in later life. Hence, this study has been conducted where pregnant Charles-Foster (CF) rats were oral gavaged with VEN (25, 40, and 50 mg/kg bw) from gestation day (GD) 05–19. On GD-19, half of the control and treated dams were euthanized to collect their fetuses. Fetal brains were dissected and processed for reactive oxygen species (ROS) estimation neurohistopathology and confocal microscopic studies. The remaining dams were allowed to deliver naturally, and litters were reared for up to 8 weeks then tested for their cognitive abilities by the Morris water maze test and for their emotionality by the Forced swimming test. Our results showed substantial neurocytoarchitectural deficits in both HPC and STR, along with enhanced ROS levels and apoptotic neurodegenerations. Furthermore, VEN-treated young rat offsprings displayed cognitive impairments and depressive behavior as the long-lasting impact of VEN in a dose-dependent manner. So it may be inferred that prenatal VEN-induced oxidative stress causes apoptotic neurodegeneration leading to neuronal loss in HPC and STR which consequently affects the development of the said brain areas resulting in impaired cognitive and emotional abilities of young adult offsprings. Therefore, extrapolating these findings in animal models, caution may be taken before prescribing VEN to pregnant women, especially during the sensitive phase of pregnancy. [ABSTRACT FROM AUTHOR]

Cholestasis is a bile flow reduction that is induced following Bile Duct Ligation (BDL). Cholestasis impairs memory and induces apoptosis. Apoptosis consists of two pathways: intrinsic and extrinsic. The intrinsic pathway is modulated by BCL-2 (B cell lymphoma-2) family proteins. BCL-2 (a pro-survival BCL-2 protein) has anti-apoptotic effect, while BAD (BCL-2-associated death) and BAX (BCL-2-associated X), the other members of BCL-2 family have pro-apoptotic effect. Furthermore, TFAM (mitochondrial transcriptional factor A) is involved in transcription and maintenance of mitochondrial DNA and PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) is a master regulator of mitochondrial biogenesis. On the other hand, NeuroAid is a Traditional Chinese Medicine with neuroprotective and anti-apoptosis effects. In this study, we evaluated the effect of cholestasis on spatial memory and expression of BCL-2, BAD, BAX, TFAM, and PGC-1α in the hippocampus of rats. Additionally, we assessed the effect of NeuroAid on cholestasis-induced cognitive and genetic alterations. Cholestasis was induced by BDL surgery and NeuroAid was injected intraperitoneal at the dose of 0.4 mg/kg. Furthermore, spatial memory was evaluated using Morris Water Maze (MWM) apparatus. The results showed cholestasis impaired spatial memory, increased the expression of BAD and BAX, decreased the expression of TFAM and PGC-1α, and did not alter the expression of BCL-2. Also, NeuroAid decreased the expression of BAD and BAX and increased the expression of TFAM, PGC-1α, and BCL-2. In conclusion, cholestasis impaired spatial memory and increased the expression of pro-apoptotic genes. Also, cholestasis decreased the expression of TFAM and PGC-1α. Interestingly, NeuroAid restored the effects of cholestasis. [ABSTRACT FROM AUTHOR]

Several studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to characterize the anatomical, neurochemical and electrophysiological properties of the SuML-DG projection neurons and to determine how they control DG oscillations and neuronal activation during PS and other vigilance states. For this purpose, we combine structural connectivity techniques using neurotropic viral vectors (rabies virus, AAV), neurochemical anatomy (immunohistochemistry, in situ hybridization) and imaging (light, electron and confocal microscopy) with in vitro (patch clamp) and in vivo (LFP, EEG) optogenetic and electrophysiological recordings performed in transgenic VGLUT2-cre male mice. At the cellular level, we show that the SuML-DG neurons co-release GABA and glutamate on dentate granule cells and increase the activity of a subset of DG granule cells. At the network level, we show that activation of the SuML-DG pathway increases theta power and frequency during PS as well as gamma power during PS and waking in the DG. At the behavioral level, we show that the activation of this pathway does not change animal behavior during PS, induces awakening during slow wave sleep and increases motor activity during waking. These results suggest that the SuML-DG pathway is capable of supporting the increase of theta and gamma power in the DG observed during PS and plays an important modulatory role of DG network activity during this state. [ABSTRACT FROM AUTHOR]

Increasing evidence points to the engagement of the lateral habenula (LHb) in the selection of appropriate behavioral responses in aversive situations. However, very few data have been gathered with respect to its role in fear memory formation, especially in learning paradigms in which brain areas involved in cognitive processes like the hippocampus (HPC) and the medial prefrontal cortex (mPFC) are required. A paradigm of this sort is trace fear conditioning, in which an aversive event is preceded by a discrete stimulus, generally a tone, but without the close temporal contiguity allowing for their association based on amygdala-dependent information processing. In a first experiment, we analyzed cellular activations (c–Fos expression) induced by trace fear conditioning in subregions of the habenular complex, HPC, mPFC and amygdala using a factorial analysis to unravel functional networks through correlational analysis of data. This analysis suggested that distinct LHb subregions engaged in different aspects of conditioning, e.g. associative processes and onset of fear responses. In a second experiment, we performed chemogenetic LHb inactivation during the conditioning phase of the trace fear conditioning paradigm and subsequently assessed contextual and tone fear memories. Whereas LHb inactivation did not modify rat's behavior during conditioning, it induced contextual memory deficits and enhanced fear to the tone. These results demonstrate the involvement of the LHb in fear memory. They further suggest that the LHb is engaged in learning about threatening environments through the selection of relevant information predictive of a danger. [ABSTRACT FROM AUTHOR]

Effect of age and ladostigil treatment (1 mg/kg/day), given for 6 months to 16 month old rats, was investigated on microglial morphology in brain regions associated with control of spatial learning. This was assessed in the Morris water maze (MWM). Microglial morphology was assessed with diaminobenzidine and fluorescent staining with Iba1 and CD11b in these brain regions. Aging did not change the number of microglia in the parietal cortex (PC) or hippocampal CA1 region (CA1-HC), but decreased microglial process tips in the CA1-HC, increased the area fraction stained by CD11b and number of bulbs on processes in PC and CA1-HC and thickness of microglial processes in corpus callosum (CC) and fornix (Fx). Performance in MWM (distance swam to escape platform) was negatively correlated with number of bulbs in PC and thickness of process in CC, and positively correlated with number of process tips in CA1-HC. Aging increased expression of MHC class II genes and others associated with motility and membrane adhesion in the PC and hippocampus, but Adora2a (Adenosine A2a receptor), only in hippocampus. Age-related increase in the number of bulbs and expression of inflammatory genes was prevented by ladostigil in PC. In the CA1-HC, ladostigil increased the number of process tips and prevented the increase in expression of Adora2a and genes regulating ion channels. Ladostigil also decreased thickening of the processes in CC and Fx. The data show brain region-specific relations induced by age in spatial learning, microglial morphology and associated genes and their response to ladostigil treatment. [ABSTRACT FROM AUTHOR]

While chronic stress induces dendritic atrophy in the hippocampus and impairs learning and memory, supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) is known to improve learning and memory of control rats. Whether n-3 PUFA supplementation improves dendritic morphology, synaptic transmission, and memory of chronically stressed rats remains unknown. In this work, we randomly assigned male Sprague-Dawley rats in four experimental groups: two unsupplemented groups, control and stress, and two supplemented groups with n-3 PUFA (DHA and EPA mix), control + n-3 PUFA and stress + n-3 PUFA. Dendritic morphology and synaptic transmission in the hippocampus were evaluated by Golgi stain and patch-clamp tools, respectively. The Y-maze and Morris water maze were used to analyze the effects of chronic stress on memory. Supplementation with n-3 PUFA improved dendritic architecture and restored the frequency of inhibitory post-synaptic currents of hippocampal pyramidal neurons of rats from stress group. In addition, n-3 PUFA supplementation improved spatial memory. Our results demonstrate that n-3 PUFA supplementation had three beneficial effects on stressed rats: prevented or compensated dendritic atrophy in CA3; restored the probability of GABA release in CA1; and improved spatial memory. We argue that n-3 PUFA supplementation can be used in treating stress-related psychiatric disorders such as depression and anxiety. [ABSTRACT FROM AUTHOR]

Aims: The aim of the study was to investigate the effects of exposure to enriched environment (EE) on passive avoidance learning and hippocampal cellular morphology in rats exposed to chronic restraint stress. Materials and Methods: Adult male albino Wistar rats were assigned into the following groups: normal control (NC) remained undisturbed in their home cages; stressed group (S) subjected to restrained stress (6 h/day) followed by housing in standard housing for 21 days; And stressed + EE (S + EE) subjected to restrained stress followed by housing in EE for 21 days. On 22nd day, six animals from each of the three groups were exposed to passive avoidance test. The remaining animals were sacrificed. Hippocampus was isolated and processed for cellular morphology using cresyl violet staining. Statistical Analysis Used: Data were analyzed using one-way analysis of variance followed by Tukey's multiple comparison test (post hoc). Results: Stressed rats exposed to EE showed significant improvement in passive avoidance learning test compared to NC. Quantification of the surviving neurons in the hippocampal subfields and their cellular morphology revealed significant neuroprotection in S + EE in cornu ammonis-2 (CA2) neurons and CA3 hippocampal neurons. No significant changes were found in CA1 hippocampal subfield. Conclusions: The outcome of this study makes us to think the possibilities of adopting EE as an alternative strategy in brain diseases where there is chronic stress and to minimize the impairment in learning and memory. [ABSTRACT FROM AUTHOR]

The hippocampus was first named in mammals based on the appearance of its gross morphological features, one end of it being fancied to resemble the head of a horse and the rest of it a silkworm, or caterpillar. A hippocampus, occupying the most medial part of the telencephalic pallium, has subsequently been identified in diverse nonmammalian taxa, but in which the "horse-caterpillar" morphology is lacking. While some strikingly similar functional similarities have been identified, questions of its homology ("sameness") across these taxa and about the very fundamental relationship of structure to function in central nervous system structures remain open. The hippocampal formation of amniotes participates in allocentric (external landmark) spatial navigation, memory, and attention to novel stimuli, and these functions generally are shared across amniotes despite variation in its morphological features. Substantially greater deviation in its morphology occurs in anamniotes, including amphibians and ray-finned fishes (actinopterygians), but its functions of allocentric spatial navigation and/or memory have been found to be preserved by studies in these taxa. Its shared functional roles cannot be used as evidence of structural homology, but given that other criteria indicate homology of the medial pallial derivative across these clades, the similar functions themselves may be regarded as homologous functions if they are based on the same cellular mechanisms and connections. The question arises as to whether the similar functions are performed by as yet undiscovered, shared morphological features or by different features that accomplish the same results via different mechanisms of neural function. [ABSTRACT FROM AUTHOR]

In mesial temporal lobe epilepsy (MTLE), spontaneous seizures likely originate from a multi-structural epileptogenic zone, including several regions of the limbic system connected to the hippocampal formation. In this study, we investigate the structural connectivity between the supramammillary nucleus (SuM) and the dentate gyrus (DG) in the model of MTLE induced by pilocarpine in the rat. This hypothalamic nucleus, which provides major extracortical projections to the hippocampal formation, plays a key role in the regulation of several hippocampus-dependent activities, including theta rhythms, memory function and emotional behavior, such as stress and anxiety, functions that are known to be altered in MTLE. Our findings demonstrate a marked reorganization of DG afferents originating from the SuM in pilocarpine-treated rats. This reorganization, which starts during the latent period, is massive when animals become epileptic and continue to evolve during epilepsy. It is characterized by an aberrant distribution and an increased number of axon terminals from neurons of both lateral and medial regions of the SuM, invading the entire inner molecular layer of the DG. This reorganization, which reflects an axon terminal sprouting from SuM neurons, could contribute to trigger spontaneous seizures within an altered hippocampal intrinsic circuitry. [ABSTRACT FROM AUTHOR]

Background: HIV-1 is a global catastrophe, and is exceedingly prevalent in Sub-Saharan Africa. HIV-associated neurocognitive disorder is characterized by symptoms such as motor impairments, a decline in cognition, and behavioural irregularities. The aim of this study was to provide insight into the fundamental behavioural and histopathological mechanisms underlying the development and progression of HIV-1 neuropathology. Methods: Using stereotaxic techniques, Tat protein Clade B (1 µg/µl, 10 µl) was injected bilaterally into the dorsal hippocampus of male Sprague-Dawley rats. The Morris water maze (MWM) and novel object recognition test (NORT) were used to assess spatial learning and recognition memory, respectively. Haematoxylin and eosin staining was used to identify the histopathological changes. Results: A highly significant increase in latency to reach the hidden platform in the MWM implied that noteworthy hippocampal damage had occurred. Severe behavioural deficits were also observed in the NORT where the Tat-injected group showed a greater preference for a familiar object over a novel one. This damage was confirmed by the histopathological changes (increased astrogliosis, cells becoming eosinophilic and a significant reduction in the pyramidal cell layer) observed in the hippocampus. Additionally, increases in the hippocampal mass and protein were observed, consistent with the structural alterations. Conclusion: This study highlights the relationship between hippocampal-associated behavioural changes and histologic alterations following stereotaxic intra-hippocampal administration of Tat protein in rats. The implications of this study may positively impact the fields of immunology and neuroscience by encouraging future researchers to consider novel strategies to understand the complexities of the pathogenesis of HIV-associated neurocognitive disorder. [ABSTRACT FROM AUTHOR]

ABSTRACT Injury to the anterior thalamic nuclei (ATN) may affect both hippocampus and retrosplenial cortex thus explaining some parallels between diencephalic and medial temporal lobe amnesias. We found that standard-housed rats with ATN lesions, compared with standard-housed controls, showed reduced spine density in hippocampal CA1 neurons (basal dendrites, −11.2%; apical dendrites, −9.6%) and in retrospenial granular b cortex (Rgb) neurons (apical dendrites, −20.1%) together with spatial memory deficits on cross maze and radial-arm maze tasks. Additional rats with ATN lesions were also shown to display a severe deficit on spatial working memory in the cross-maze, but subsequent enriched housing ameliorated their performance on both this task and the radial-arm maze. These enriched rats with ATN lesions also showed recovery of both basal and apical CA1 spine density to levels comparable to that of the standard-housed controls, but no recovery of Rgb spine density. Inspection of spine types in the CA1 neurons showed that ATN lesions reduced the density of thin spines and mushroom spines, but not stubby spines; while enrichment promoted recovery of thin spines. Comparison with enriched rats that received pseudo-training, which provided comparable task-related experience, but no explicit spatial memory training, suggested that basal CA1 spine density in particular was associated with spatial learning and memory performance. Distal pathology in terms of reduced integrity of hippocampal and retrosplenial microstructure provides clear support for the influence of the ATN lesions on the extended hippocampal system. The reversal by postoperative enrichment of this deficit in the hippocampus but not the retrosplenial cortex may indicate region-specific mechanisms of recovery after ATN injury. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A wide variety of species, including vertebrate and invertebrates, consume food in bouts (i.e., meals). Decades of research suggest that different mechanisms regulate meal initiation (when to start eating) versus meal termination (how much to eat in a meal, also known as satiety). There is a very limited understanding of the mechanisms that regulate meal onset and the duration of the postprandial intermeal interval (ppIMI). In the present review, we examine issues involved in measuring meal onset and some of the limited available evidence regarding how it is regulated. Then, we describe our recent work indicating that dorsal hippocampal neurons inhibit meal onset during the ppIMI and describe the processes that may be involved in this. We also synthesize recent evidence, including evidence from our laboratory, suggesting that overeating impairs hippocampal functioning and that impaired hippocampal functioning, in turn, contributes to the development and/or maintenance of diet-induced obesity. Finally, we identify critical questions and challenges for future research investigating neural controls of meal onset. [ABSTRACT FROM AUTHOR]

Episodic memory incorporates information about specific events or occasions including spatial locations and the contextual features of the environment in which the event took place. It has been modeled in rats using spontaneous exploration of novel configurations of objects, their locations, and the contexts in which they are presented. While we have a detailed understanding of how spatial location is processed in the brain relatively little is known about where the nonspatial contextual components of episodic memory are processed. Initial experiments measured c-fos expression during an object-context recognition (OCR) task to examine which networks within the brain process contextual features of an event. Increased c-fos expression was found in the lateral entorhinal cortex (LEC; a major hippocampal afferent) during OCR relative to control conditions. In a subsequent experiment it was demonstrated that rats with lesions of LEC were unable to recognize object-context associations yet showed normal object recognition and normal context recognition. These data suggest that contextual features of the environment are integrated with object identity in LEC and demonstrate that recognition of such object-context associations requires the LEC. This is consistent with the suggestion that contextual features of an event are processed in LEC and that this information is combined with spatial information from medial entorhinal cortex to form episodic memory in the hippocampus. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]