Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memory

Lesions restricted to the dorsal, but not the ventral, hippocampus severely impair the formation of spatial memory. This dissociation was first demonstrated using the water maze task. The present study investigated whether the dorsal and the ventral hippocampus are involved differentially in spatial reference and spatial working memory using a four-baited/four-unbaited version of the eight-arm radial maze task. This test allows the concurrent evaluation of reference and working memory with respect to the same set of spatial cues, and thereby enables a within-subjects within-task comparison between the two forms of memory functions. Rats with N-methyl-d-aspartic acid-induced excitotoxic lesions of the dorsal hippocampus, ventral hippocampus or both were compared with sham and unoperated controls. We showed that dorsal lesions were as effective as complete lesions in severely disrupting both reference and working spatial memory, whereas rats with ventral lesions performed at a level comparable with controls. These results lend further support to the existence of a functional dissociation between the dorsal and the ventral hippocampus, with the former being preferentially involved in spatial learning.     

Small lesions of the dorsal or ventral hippocampus subregions are associated with distinct impairments in working memory and reference memory retrieval,and combining them attenuates the acquisition rate of spatial reference memory

The importance of the hippocampus in spatial learning is well established, but the precise relative contributions by the dorsal (septal) and ventral (temporal) subregions remain unresolved. One debate revolves around the extent to which the ventral hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal hippocampus or ventral hippocampus alone (destroying 18.9 and 28.5% of total hippocampal volume, respectively) spared reference memory acquisition in the water maze. By contrast, combining the two subtotal lesions significantly reduced the rate of acquisition across days. This constitutes evidence for synergistic integration between dorsal and ventral hippocampus in mice. Evidence that ventral hippocampus contributes to spatial/navigation learning also emerged early on during the retention probe test as search preference was reduced in mice with ventral lesions alone or combined lesions. The small ventral lesions also led to anxiolysis in the elevated plus maze and over‐generalization of the conditioned freezing response to a neutral context. Similar effects of comparable magnitudes were seen in mice with combined lesions, suggesting that they were largely due to the small ventral damage. By contrast, small dorsal lesions were uniquely associated with a severe spatial working memory deficit in the water maze. Taken together, both dorsal and ventral poles of the hippocampus contribute to efficient spatial navigation in mice: While the integrity of dorsal hippocampus is necessary for spatial working memory, the acquisition and retrieval of spatial reference memory are modulated by the ventral hippocampus. Although the impairments following ventral damage (alone or in combination with dorsal damage) were less substantial, a wider spectrum of spatial learning, including context conditioning, was implicated. Our results encourage the search for integrative mechanism between dorsal and ventral hippocampus in spatial learning. Candidate neural substrates may include dorsoventral longitudinal connections and reciprocal modulation via overlapping polysynaptic networks beyond hippocampus.     

Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks

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.     

Functional differentiation in the hippocampus

The hippocampus is critically involved in certain kinds of memory. During memory formation, it may operate as an integrated unit, or isolated parts may be responsible for different functions. Recent evidence suggests that the hippocampus is functionally differentiated along its dorsoventral (septotemporal) axis. The cortical and subcortical connections of the dorsal and ventral hippocampus are different, with information derived from the sensory cortices entering mainly in the dorsal two-thirds or three-quarters of the dentate gyrus. Rats can acquire a spatial navigation task if small tissue blocks are spared within this region, but equally large blocks at the ventral end are not capable of supporting spatial learning. In primates, the posterior hippocampus (corresponding to the dorsal hippocampus of rodents) appears to be more important than anterior areas for encoding of spatial memory and certain forms of nonspatial memory. The ventral (or anterior) hippocampal formation is to some extent disconnected from the rest of the structure both in terms of intrahippocampal and extrahippocampal connections and may be performing functions that are qualitatively different from, and independent of, those of the dorsal hippocampal formation. Hippocampus 1998;8:608–619. © 1998 Wiley-Liss, Inc.     

Dissociating space and trace in dorsal and ventral hippocampus

Emerging evidence suggests that the hippocampus can be anatomically and functionally dissociated along its septotemporal axis into dorsal and ventral subregions. With respect to function, we have recently demonstrated that pre-training excitotoxic lesions of ventral, but not dorsal, hippocampus impair the acquisition of trace fear conditioning, whereas post-training lesions of either dorsal or ventral hippocampus impair the subsequent expression of trace fear conditioning (Yoon and Otto (2007) Neurobiol Learn Mem 87:464-475). In addition to trace fear conditioning, dorsal and ventral hippocampus appear to be differentially involved in a number of spatial memory tasks. The present study examined the effects of temporary inactivation of dorsal or ventral hippocampus on the acquisition and expression of trace fear conditioning and on performance of a spatial delayed reinforced alternation task. The findings demonstrate a double dissociation of dorsal and ventral hippocampal function: inactivation of ventral, but not dorsal, hippocampus attenuated the acquisition and expression of trace fear conditioning, whereas inactivation of dorsal, but not ventral, hippocampus dramatically impaired performance in the delayed reinforced alternation task. These data further support the notion that dorsal and ventral hippocampus contribute differentially to performance in a variety of paradigms.     

Reduced thyroid hormones with increased hippocampal SNAP-25 and Munc18-1 might involve cognitive impairment during aging

The mechanism underlying the decline of age-related learning and memory remains unclear. Brain-region-specific changes of synaptic proteins and decreased thyroid hormones (THs) have been implied involving this decline. During normal aging, however, the relationships among synaptic proteins, THs and abilities of learning and memory remain to be elucidated. In this study, the age-related spatial learning and memory ability of 41 Kunming mice (KM) (14 mice aged 6 months, 13 mice aged 11 months, 14 mice aged 22 months) was measured with radial six-arm water maze. The levels of SNAP-25 and Munc18-1 in brain regions were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay. Our results showed the old Kunming mice had marked impairment of spatial learning and memory, with decreased serum free triiodothyronine (FT3) and increased SNAP-25 and Munc18-1 in dorsal hippocampus (DH), ventral hippocampus (VH) and frontal lobe (F). The Pearson's correlation test showed the impairment of spatial learning ability positively correlated with SNAP-25 in DH and Munc18-1 in DH and VH. While, the levels of SNAP-25 (DH, VH and F) and Munc18-1 (DH) negatively correlated with the serum FT3 level, and the spatial memory decline marginal negatively correlate with serum THs. These results suggested that increased hippocampal SNAP-25 and Munc18-1 which seemingly result from decreased serum THs might involve the age-related impairment of spatial learning and memory.     

Acute stress-induced impairment of spatial memory is associated with decreased expression of neural cell adhesion molecule in the hippocampus and prefrontal cortex.

BACKGROUND: There is an extensive literature describing how stress disturbs cognitive processing and can exacerbate psychiatric disorders. There is, however, an insufficient understanding of the molecular mechanisms involved in stress effects on brain and behavior. METHODS: Rats were given spatial memory training in a hippocampus-dependent water maze task. We investigated how a fear-provoking experience (predator exposure) would affect their spatial memory and neural cell adhesion molecule (NCAM) levels in the hippocampus, prefrontal cortex (PFC), amygdala, and cerebellum. RESULTS: Whereas the control (nonstress) group exhibited excellent memory for the hidden platform location in the water maze, the cat-exposed (stress) group exhibited a profound impairment of memory and a marked suppression of levels of the NCAM-180 isoform in the hippocampus. Predator stress produced a more global reduction of NCAM levels in the PFC but had no effect on NCAM levels in the amygdala and cerebellum. CONCLUSIONS: This work provides a novel perspective into dynamic and structure-specific changes in the molecular events involved in learning, memory, and stress. The selective suppression of NCAM-180 in the hippocampus and the more general suppression of NCAM in the PFC provide insight into the mechanisms underlying the great sensitivity of these two structures to be disturbed by stress.     

Influence of differential housing on emotional behaviour and neurotrophin levels in mice

Environmental enrichment condition (EC) induces profound behavioural, neurochemical and neuroanatomical changes. Increasing evidence has shown that the hippocampus, which is implicated in a range of cognitive functions, including learning and memory, is one of the most susceptible brain areas to the effects of enriched rearing. Recent work also suggests that the hippocampus is functionally segregated; lesion studies have shown that the dorsal hippocampus is important for spatial learning, whereas the ventral part is critical in emotional behaviour in rats. We investigated the effects of differential housing environments on anxiety-related behaviour and neurotrophin levels in dorsal and ventral hippocampus, and other brain regions. Ninety-six male and female C57BL/6 mice were reared in EC or standard housing condition (SC) for 4 months after weaning. Thereafter sixty-four animals were tested in the elevated plus-maze, open-field, novel-objects exploration and food neophobia. Thirty-two animals remained as untested. Subsequently, brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were analysed in selected brain regions of the tested and non-tested animals. Differential housing influenced anxiety-related behaviour in the plus-maze and brain neurotrophins. Baseline levels of BDNF and NGF protein were differently distributed in dorsal and ventral parts of hippocampus in both male and female mice, with levels in the dorsal hippocampal being consistently higher than those in ventral hippocampus. Exposure to behavioural testing induced complex changes on neurotrophin levels in selected brain regions. This study demonstrates for the first time the differential distribution of normal levels of neurotrophin protein in dorsal and ventral hippocampus in mice, and these levels can be affected by environmental enrichment and have an impact on emotional behaviour.     

Brain system size and adult-adult play in primates: a comparative analysis of the roles of the non-visual neocortex and the amygdala

We investigated the relationship between the degree of spatial memory impairment in an 8-arm radial maze and the changes in the contents of acetylcholine (ACh) and noradrenaline (NA) in the dorsal and ventral hippocampus and the frontal cortex, along with histological changes in kaolin-induced hydrocephalic rats. Kaolin-induced hydrocephalic rats were divided into three groups (non-impaired, impaired and severely impaired) according to the degree of impairment in a radial maze. Thirty percent of the hydrocephalic rats could not solve a radial maze (severely impaired group), while the remaining hydrocephalic rats could (non-impaired rats in the standard task). Forty percent of the non-impaired rats in the standard task failed to solve the delayed-response task (impaired group), whereas the remaining rats were able to solve it (non-impaired group). A positive correlation was observed between the impairment of spatial memory and ventricular dilatation. The ACh content in the dorsal and ventral hippocampus, and the NA content in the ventral hippocampus were decreased in the severely impaired group. Moreover, the NA content in the ventral hippocampus was decreased in the impaired group. These results suggest that the impairment of spatial memory in kaolin-induced hydrocephalic rats is associated with dysfunction of the hippocampal cholinergic and noradrenergic systems.     

A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum

The objectives of this research were to further delineate the neural circuits subserving proposed memory-based behavioural subsystems in the hippocampal formation. These studies were guided by anatomical evidence showing a topographical organization of the hippocampal formation. Briefly, perpendicular to the medial/lateral entorhinal cortex division there is a second system of parallel circuits that separates the dorsal and ventral hippocampus. Recent work from this laboratory has provided evidence that the hippocampus incidentally encodes a context-specific inhibitory association during acquisition of a visual discrimination task. One question that emerges from this dataset is whether the dorsal or ventral hippocampus makes a unique contribution to this newly described function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were assessed on the acquisition of the visual discrimination task. Following asymptotic performance they were given reversal training in either the same or a different context from the original training. The results showed that the context-specific inhibition effect is mediated by a circuit that includes the ventral but not the dorsal hippocampus. Results from a control procedure showed that rats with either dorso-lateral striatum damage or dorsal hippocampal lesions were impaired on a tactile/spatial discrimination. Taken together, the results represent a double dissociation of learning and memory function between the ventral and dorsal hippocampus. The formation of an incidental inhibitory association was dependent on ventral but not dorsal hippocampal circuitry, and the opposite dependence was found for the spatial component of a tactile/spatial discrimination.     

Decreased glutamate release correlates with elevated dynorphin content in the hippocampus of aged rats with spatial learning deficits.

The effects of aging on extracellular glutamate and tissue dynorphin content in the hippocampus were examined in Fischer-344 rats. Young adult (4-month-old) and aged (24-month-old) rats were trained to find a hidden platform in the Morris water task. Aged rats were unable to acquire the spatial learning task as rapidly as young controls. Following behavioral testing, an in vivo microdialysis perfusion method was used to determine extracellular glutamate levels in the hippocampus. There was a 25-35% reduction in extracellular glutamate concentration in both dorsal and ventral hippocampus of aged rats compared to young rats, in the absence of any change in tissue glutamate levels. Radioimmunoassay showed an increase in dynorphin A(1-8)-like immunoreactivity [DYN-A(1-8)LI] in both dorsal and ventral hippocampus, but not striatum, of aged rats. Immunocytochemistry indicated that this increase was localized to the dentate granule cells and mossy fibers. Furthermore, among the aged rats the increase in DYN-A(1-8)LI was inversely correlated with the decrease in extracellular glutamate. These results suggest that the disregulation of dynorphin observed in cognitively impaired aged rats is related to reduced excitatory transmission within the hippocampal formation.     

Post‐training,intrahippocampal HDAC inhibition differentially impacts neural circuits underlying spatial memory in adult and aged mice

Converging evidence indicates that pharmacologically elevating histone acetylation using post‐training, systemic or intrahippocampal, administration of histone deacetylase inhibitor (HDACi) can enhance memory consolidation processes in young rodents but it is not yet clear, whether such treatment is sufficient to prevent memory impairments associated with aging. To address this question, we used a 1‐day massed spatial learning task in the water maze to investigate the effects of immediate post‐training injection of the HDACi trichostatin A (TSA) into the dorsal hippocampus on long‐term memory consolidation in 3–4 and 18–20 month‐old mice. We show that TSA improved the 24 h‐memory retention for the hidden platform location in young‐adults, but failed to rescue memory impairments in older mice. The results further indicate that Young‐TSA mice sacrificed 1 h after training had a robust increase in histone H4 acetylation in the dorsal hippocampal CA1 region (dCA1) and the dorsomedial part of the striatum (DMS), a structure important for spatial information processing. Importantly, TSA infusion in aged mice completely rescued altered H4 acetylation in the dCA1 but failed to alleviate age‐associated decreased H4 acetylation in the DMS. Moreover, intrahippocampal TSA infusion produced concomitant decreases (in adults) or increases (in older mice) of acetylated histone levels in the ventral hippocampus (vCA1 and vCA3) and the lateral amygdala, two structures critically involved in stress and emotional responses. These data suggest that the failure of post‐training, intrahippocampal TSA injection to reverse age‐associated memory impairments may be related to an inability to recruit appropriate circuit‐specific epigenetic patterns during early consolidation processes. © 2014 Wiley Periodicals, Inc.     

快速老化痴呆模型小鼠SAMP8学习记忆能力的增龄性变化

目的对快速老化痴呆模型小鼠SAMP8学习记忆能力的增龄性变化进行较系统的研究,为利用该模型进行其他研究提供实验依据。方法此实验选用1、4、8、12月龄的快速老化痴呆模型小鼠SAMP8,与同龄的正常老化小鼠SAMR1作对照,从老化度评分、避暗实验、Morris水迷宫实验和自主活动实验等方面观察了SAMP8小鼠学习记忆能力的增龄性变化。结果与对照组SAMR1相比,SAMP8小鼠随月龄增加老化度评分呈增高趋势,在8、12月龄的老化度评分值显著高于同龄对照组(P<0.05);避暗实验中,8、12月龄的SAMP8小鼠在电击24h后进入暗箱的潜伏期比同龄SAMR1小鼠显著缩短(P<0.05);Morris水迷宫实验中,1、4月龄SAMP8小鼠找到暗台的潜伏时间与同龄SAMR1小鼠相比差异无显著性,而8、12月龄SAMP8小鼠与同龄对照组相比,潜伏时间显著延长(P<0.05);从自主活动实验看,1、4、8月龄SAMP8小鼠单位时间内自主活动次数与同龄SAMR1小鼠相比无显著变化,而12月龄SAMP8小鼠与同龄对照组相比单位时间内自主活动次数显著减少(P<0.05)。结论SAMP8小鼠随月龄增长学习记忆能力逐渐减退;与同龄对照组相比,8、12月龄SAMP8小鼠出现明显衰老特征,表现出学习记忆能力明显低下,故可作为老化痴呆的动物模型用于痴呆有关研究。     

Region‐ and age‐specific patterns of histone acetylation related to spatial and cued learning in the water maze

Epigenetic processes, such as histone acetylation, are critical regulators of learning and memory processes. In the present study, we investigated whether training in either a spatial or a cued water maze task undergoes selective changes of histone H3 and H4 acetylation within the hippocampus and the dorsal striatum of C57BL/6 mice. We also attempted to provide new insights into the relationships between deregulation in histone acetylation and age‐associated memory deficits. In young mice, spatial training increased acetylation of histones H3 and H4 selectively in the dorsal hippocampal CA1 region and the dentate gyrus (DG) whereas cued training significantly enhanced acetylation of both histones selectively in the dorsal striatum. Our data also revealed age‐related differences in histone acetylation within the hippocampus and striatum according to task demands. Specifically, age‐related spatial memory deficits were associated with opposite changes of H3 (increase) and H4 (decrease) acetylation in CA1 and DG. After cued learning, both histone acetylation levels were reduced in the striatum of aged mice compared with corresponding young‐adults but remained well above those of cage‐controls. Collectively, our findings suggest an important role for histone acetylation in regulating the relative contributions of the hippocampus and striatum to learning spatial and cued memory tasks. © 2013 Wiley Periodicals, Inc.     

Changes in expressions of proinflammatory cytokines IL-1beta, TNF-alpha and IL-6 in the brain of senescence accelerated mouse (SAM) P8

The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. The SAMP8 strain shows age-related deterioration of learning and memory at an earlier age than control mice (SAMR1). In the present study, we investigated the changes in expressions of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the brain of SAMP8. In the hippocampus of 10 months old SAMP8, the expression of IL-1 mRNA was significantly elevated in comparison with that of SAMR1. In both strains of SAMs, increases in IL-1beta protein in the brain were observed at 10 months of age compared with 2 and 5 months. The only differences found between the strain in protein levels were at 10 months and were elevations in IL-1beta in the hippocampus and hypothalamus, and in TNF-alpha and IL-6 in the cerebral cortex and the hippocampus in SAMP8 as compared with SAMR1. However, lipopolysaccharide-induced increases in the expression of these cytokines in brain did not differ between SAMP8 and SAMR1. Increases in expression of proinflammatory cytokines in the brain may be involved in the age-related neural dysfunction and/or learning deficiency in SAMP8.     

The role of the ventral dentate gyrus in olfactory pattern separation

Dorsoventral lesion studies of the hippocampus have indicated that the dorsal axis of the hippocampus is important for spatial processing and the ventral axis of the hippocampus is important for olfactory learning and memory and anxiety. There is some evidence to suggest that the ventral CA3 and ventral CA1 conduct parallel processes for pattern completion and temporal processing, respectively. Studies have indicated that the dorsal dentate gyrus (DG) is importantly involved in processes reflecting underlying pattern separation activity for spatial information. However, the ventral DG is less understood. The current study investigated the less‐understood role of the ventral DG in olfactory pattern separation. A series of odor stimuli that varied on only one level, number of carbon chains (methyl groups), was used in a matching‐to‐sample paradigm in order to investigate ventral DG involvement in working memory for similar and less similar odors. Rats with ventral DG lesions were impaired at delays of 60 sec, but not at delays of 15 sec. A memory‐based pattern separation effect was observed performance was poorest with only one carbon chain separation between trial odors and was highest for trials with four separations. The present study indicates that the ventral DG plays an important role in olfactory learning and memory processes for highly similar odors. The results also indicate a role for the ventral DG in pattern separation for odor information, which may have further implications for parallel processing across the dorsoventral axis for the DG in spatial (dorsal) and olfactory (ventral) pattern separation. © 2014 Wiley Periodicals, Inc.     

Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats

Substantial information is available concerning the influence of global hippocampal lesions on spatial learning and memory, however the contributions of discrete subregions within the hippocampus to these functions is less well understood. The present investigation utilized kainic acid to bilaterally lesion specific areas of the rat hippocampus. These animals were subsequently tested on a spatial orientation task using a circular water maze, and on an associative/contextual task using passive avoidance conditioning. The results indicate that both the dorsal CA1 and the ventral CA3 subregions play important roles in learning. Specifically, CA1 lesions produced a deficit in the acquisition of the water maze task and a significant memory impairment on the passive avoidance task. CA3 lesions also caused learning deficits in the acquisition of the water maze task, and produced even greater impairments in performance on the passive avoidance task. We conclude that CA1 and CA3 hippocampal subregions each play significant roles in the overall integration of information concerning spatial and associative learning.     

Nicotinic receptors in the dorsal and ventral hippocampus differentially modulate contextual fear conditioning

Nicotine administration alters various forms of hippocampus‐dependent learning and memory. Increasing work has found that the dorsal and ventral hippocampus differentially contribute to multiple behaviors. Thus, the present study examined whether the effects of nicotine in the dorsal and ventral hippocampus have distinct influences on contextual fear learning in male C57BL/6J mice. Direct infusion of nicotine into the dorsal hippocampus resulted in an enhancement of contextual fear learning, whereas nicotine infused into the ventral hippocampus resulted in deficits. Nicotine infusions into the ventral hippocampus did not alter hippocampus‐independent cued fear conditioning or time spent in the open arm of the elevated plus maze, a measure of anxiety, suggesting that the effects are due to alterations in contextual learning and not other general processes. Finally, results from using direct infusions of MLA, a low‐affinity α7 nicotinic acetylcholine receptor (nAChR) antagonist, in conjunction with systemic nicotine, provide evidence that α7‐nAChRs in the ventral hippocampus mediate the detrimental effect of ventral hippocampal nicotine on contextual fear learning. These results suggest that with systemic nicotine administration, competition exists between the dorsal and ventral hippocampus for behavioral control over contextual learning. © 2012 Wiley Periodicals, Inc.     

Changes in expressions of proinflammatory cytokines IL-1β, TNF-α and IL-6 in the brain of senescence accelerated mouse (SAM) P8

The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. The SAMP8 strain shows age-related deterioration of learning and memory at an earlier age than control mice (SAMR1). In the present study, we investigated the changes in expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the brain of SAMP8. In the hippocampus of 10 months old SAMP8, the expression of IL-1 mRNA was significantly elevated in comparison with that of SAMR1. In both strains of SAMs, increases in IL-1β protein in the brain were observed at 10 months of age compared with 2 and 5 months. The only differences found between the strain in protein levels were at 10 months and were elevations in IL-1β in the hippocampus and hypothalamus, and in TNF-α and IL-6 in the cerebral cortex and the hippocampus in SAMP8 as compared with SAMR1. However, lipopolysaccharide-induced increases in the expression of these cytokines in brain did not differ between SAMP8 and SAMR1. Increases in expression of proinflammatory cytokines in the brain may be involved in the age-related neural dysfunction and/or learning deficiency in SAMP8.     

Behavioral effects of arginine8-vasopressin in the Hebb-Williams maze

Arginine(8)-vasopressin (AVP) has been shown to improve memory consolidation in various mnemonic tasks. Our previous studies have pointed out the involvement of the hippocampus (with higher sensitivity of its ventral part) in memory consolidation and retrieval processes during discriminative learning in mice. The present study was designed to extend our knowledge, firstly, of the range of tasks and consequently the types of information for which the peptide improves consolidation processes, and secondly, the effects of AVP on information treatment processes such an information transfer. To this end, the effects of AVP were analyzed in the Hebb-Williams closed-field maze. Mice were initially trained on one of the mazes in the Hebb-Williams series (Maze 7) and subsequently tested on either that maze or another maze in the series (Maze 11). The effects of the peptide on both memory consolidation and information transfer processes were analyzed in relation to the route of administration: peripheral (subcutaneous, s.c.), central (intracerebroventricular, i.c.v.), and in situ (dorsal or ventral hippocampus). The results showed that AVP facilitated spatial memory consolidation following s.c., i.c.v, and dorsal, but not ventral hippocampal administration. This differential effect of AVP following injection into the hippocampus can be interpreted in regards to this structure's functions. In line with the involvement of the dorsal hippocampus in spatial memory, the effectiveness of the peptide in the Hebb-Williams maze, which contains spatial components, was better when the treatment was performed in this part of the structure. In contrast, whatever the route of administration, AVP had no effect on processes related to the transfer from one learning situation to another.