Role Of Hippocampus Research Articles

A Brain System for Auditory Working Memory

The brain basis for auditory working memory, the process of actively maintaining sounds in memory over short periods of time, is controversial. Using functional magnetic resonance imaging in human participants, we demonstrate that the maintenance of single tones in memory is associated with activation in auditory cortex. In addition, sustained activation was observed in hippocampus and inferior frontal gyrus. Multivoxel pattern analysis showed that patterns of activity in auditory cortex and left inferior frontal gyrus distinguished the tone that was maintained in memory. Functional connectivity during maintenance was demonstrated between auditory cortex and both the hippocampus and inferior frontal cortex. The data support a system for auditory working memory based on the maintenance of sound-specific representations in auditory cortex by projections from higher-order areas, including the hippocampus and frontal cortex. In this work, we demonstrate a system for maintaining sound in working memory based on activity in auditory cortex, hippocampus, and frontal cortex, and functional connectivity among them. Specifically, our work makes three advances from the previous work. First, we robustly demonstrate hippocampal involvement in all phases of auditory working memory (encoding, maintenance, and retrieval): the role of hippocampus in working memory is controversial. Second, using a pattern classification technique, we show that activity in the auditory cortex and inferior frontal gyrus is specific to the maintained tones in working memory. Third, we show long-range connectivity of auditory cortex to hippocampus and frontal cortex, which may be responsible for keeping such representations active during working memory maintenance.

TRH modulates glutamatergic synaptic inputs on CA1 neurons of the mouse hippocampus in a biphasic manner

Thyrotropin Releasing Hormone (TRH) is a tripeptide that induces the release of Thyroid Stimulating Hormone (TSH) in the blood. Besides its role in the thyroid system, TRH has been shown to regulate several neuronal systems in the brain however its role in hippocampus remains controversial. Using electrophysiological recordings in acute mouse brain slices, we show that TRH depresses glutamate responses at the CA3-CA1 synapse through an action on NMDA receptors, which, as a consequence, decreases the ability of the synapse to establish a long term potentiation (LTP). TRH also induces a late increase in AMPA/kainate responses. Together, these results suggest that TRH plays an important role in the modulation of hippocampal neuronal activities, and they contribute to a better understanding of the mechanisms by which TRH impacts synaptic function underlying emotional states, learning and memory processes.

Inhibition of hippocampal plasticity in rats performing contrafreeloading for water under repeated administrations of pramipexole.

Compulsive symptoms develop in patients exposed to pramipexole (PPX), a dopaminergic agonist with high selectivity for the D3 receptor. Consistently, we demonstrated that PPX produces an exaggerated increase in contrafreeloading (CFL) for water, a repetitive and highly inflexible behavior that models core aspects of compulsive disorders. Given the role of the hippocampus in behavioral flexibility, motivational control, and visuospatial working memory, we investigated the role of hippocampus in the expression of PPX-induced CFL. To this aim, rats were subjected to CFL under chronic PPX, and then examined for the electrophysiological, structural, and molecular properties of their hippocampus. We measured long-term potentiation (LTP) at CA1 Schaffer collaterals, dendritic spine density in CA1 pyramidal neurons, and then glutamate release and expression of pre and postsynaptic proteins in hippocampal synaptosomes. The effects of PPX on hippocampal-dependent working memory were assessed through the novel object recognition (NOR) test. We found that PPX-treated rats showing CFL exhibited a significant decrease in hippocampal LTP and failed to exhibit the expected increase in hippocampal spine density. Glutamate release and PSD-95 expression were decreased, while pSYN expression was increased in hippocampal synaptosomes of PPX-treated rats showing CFL. Despite a general impairment of hippocampal synaptic function, working memory was unaffected by PPX treatment. Our findings demonstrate that chronic PPX affects synaptic function in the hippocampus, an area that is critically involved in the expression of flexible, goal-centered behaviors. We suggest that the hippocampus is a promising target in the pharmacotherapy of compulsive disorders.

Evidences of the role of the rodent hippocampus in the non-spatial recognition memory

The hippocampus is a key region responsible for processing spatial information. However, the role of the hippocampus in non-spatial recognition memory is still controversial. In the present study, we performed hippocampal lesioning to address this controversy. The hippocampi of mice were disrupted with bilateral cytotoxic lesions, and standard object recognition (non-spatial) and object location recognition (spatial) were tested. In the habituation period, mice with hippocampal lesions needed a significantly longer time to fully habituate to the test box. Interestingly, after 4 days of habituation (insufficient habituation), the recognition index was similar in the sham and hippocampal lesion groups. However, exploration time was significantly shorter in mice with hippocampal lesions compared with that in control mice. Interestingly, if mice were subjected to a 10-days-long period of habituation (full habituation), the recognition index was significantly lower in mice with hippocampal lesions compared with that in control mice; however, total exploration time was similar in both groups. Furthermore, the object recognition test after full habituation occluded hippocampal long-term potentiation, a cellular model of memory. These results indicate that sufficient habituation is required to observe the effects of hippocampal lesions on object recognition memory.

The hippocampus and executive functions in depression.

Background:The relationship between depression, hippocampus (HC), and executive dysfunctions seems complex and has been the focus of research. Recent evidence indicates a possible role of HC in executive dysfunction seen in depression. No such studies on Indian population have been done.Aim:To look for changes in HC and executive functions in depression.Settings and Design:A cross-sectional analytical controlled study. Sample size 50 (controls 50).Materials and Methods:Hippocampal volume and executive dysfunction was measured using structural magnetic resonance imaging (MRI) and Wisconsin Card Sorting Test (WCST), respectively. Findings on these two parameters were compared between depressives and healthy matched controls as well as between first episode (FE) and recurrent depressives and across the severity of depression (mild, moderate, and severe).Statistical Analysis:Statistical Package for Social Sciences (SPSS) version 17 was used for analysis. Normally distributed continuous variables were analyzed with independent t-tests. Analysis of variance (ANOVA) was used for multiple comparisons. Categorical data were compared with χ2 or Fisher's exact test. Clinical correlations were conducted using Pearson correlations.Result:Depressed patients had a smaller left (Lt) hippocampal volume as well as poor performance on several measures of executive functions. Smaller hippocampal volume was found even in FE. Those who had a past burden of depressive illness had an even smaller hippocampal volume. No direct correlation was found between the HC volume and cognitive dysfunction.Conclusion:Depressive illness appears to be toxic to the HC. The relationship between HC and executive dysfunction in depression may be indirect through its functional connections.

Predicting rapid response to cognitive-behavioural treatment for panic disorder: The role of hippocampus, insula, and dorsolateral prefrontal cortex

Although cognitive-behavioural therapy (CBT) is an effective first-line intervention for anxiety disorders, treatments remain long and cost-intensive, difficult to access, and a subgroup of patients fails to show any benefits at all. This study aimed to identify functional and structural brain markers that predict a rapid response to CBT. Such knowledge will be important to establish the mechanisms underlying successful treatment and to develop more effective, shorter interventions. Fourteen unmedicated patients with panic disorder underwent 3 T functional and structural magnetic resonance imaging (MRI) before receiving four sessions of exposure-based CBT. Symptom severity was measured before and after treatment. During functional MRI, patients performed an emotion regulation task, either viewing negative images naturally, or intentionally down-regulating negative affect by using previously taught strategies of cognitive reappraisal. Structural MRI images were analysed including left and right segmentation and volume estimation. Improved response to brief CBT was predicted by increased pre-treatment activation in bilateral insula and left dorsolateral prefrontal cortex (dlPFC) during threat processing, as well as increased right hippocampal gray matter volume. Previous work links these regions to improved threat processing and fear memory activation, suggesting that the activation of such mechanisms is crucial for exposure-based CBT to be effective.

传递性推理的神经机制研究

探讨高级认知过程(如推理、问题解决等)的神经机制已经成为目前心理学研究的热点，文章回顾并总结了近年来对传递性推理的神经机制的研究进展，具体内容涉及：1) 传递性推理与非传递性推理作用脑区的差异；2) 不同项数和材料激活脑区的差异；3) 海马在传递性推理中的作用；4) 传递性推理的神经环路。立足对研究现状的逐层深入思考，文章最后对传递性推理神经机制的未来研究方向和方法进行了展望。 Probing the neural mechanism of advanced cognitive progresses (such as inference, problem solving, etc.) has become the hot issue of current psychological research. This article reviewed the latest researches on the neural mechanisms of transitive inference: 1) transitive inference and non-transitive inference will result in different activation; 2) different material and number of item of transitive reasoning will result in different activation; 3) the role of hippocampus in the transitive inference; and 4) there is a neural circuitry of transitive inference. In the end, some frequently used methods were listed and some reflections were provided for the future.

Hippocampal NMDA receptor blockade impairs CREB phosphorylation in amygdala after contextual fear conditioning

In contextual fear conditioning (CFC), hippocampus is thought to process environmental stimuli into a configural representation of the context and send it to amygdala nuclei, which current evidences point to be the site of CS-US association and fear memory storage. If it is true, hippocampus should influence learning-induced plasticity in the amygdala nuclei after CFC acquisition. To test this, we infused wistar rats with saline or AP5, a NMDA receptor antagonist, in the dorsal hippocampus just before a CFC session, in which they were conditioned to a single shock, exposed to the context with no shocks or received an immediate shock. The rats were perfused, their brains harvested and immunohistochemically stained for cAMP element binding protein (CREB) phosphorylation ratio (pCREB/CREB) in lateral (LA), basal (B) and central (CeA) amygdala nuclei. CFC showed a learning-specific increase in pCREB ratio in B and CeA, in conditioned-saline rats compared to context and immediate shocked ones. Further, conditioned rats that received AP5 showed a decrease in pCREB ratio in LA, B and CeA. Our results support the current ideas that the role of hippocampus in contextual fear conditioning occurs by sending contextual information to amygdala to serve as conditioned stimulus.

Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most prevalent form of focal epilepsy, and hippocampal sclerosis (HS) is considered the most frequent associated pathological finding. Recent connectivity studies have shown that abnormalities, either structural or functional, are not confined to the affected hippocampus, but can be found in other connected structures within the same hemisphere, or even in the contralesional hemisphere. Despite the role of hippocampus in memory functions, most of these studies have explored network properties at resting state, and in some cases compared connectivity values with neuropsychological memory scores. Here, we measured magnetoencephalographic responses during verbal working memory (WM) encoding in left mTLE patients and controls, and compared their effective connectivity within a frontotemporal network using dynamic causal modelling. Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal cortex (IFC), and the medial temporal lobe (MTL). Test for differences in effective connectivity revealed that patients exhibited decreased ipsilesional MTL-ITC backward connectivity, and increased bidirectional IFC-MTL connectivity in the contralesional hemisphere. Critically, a negative correlation was observed between these changes in patients, with decreases in ipsilesional coupling among temporal sources associated with increases contralesional frontotemporal interactions. Furthermore, contralesional frontotemporal interactions were inversely related to task performance and level of education. The results demonstrate that unilateral sclerosis induced local and remote changes in the dynamic organization of a distributed network supporting verbal WM. Crucially, pre-(peri) morbid factors (educational level) were reflected in both cognitive performance and (putative) compensatory changes in physiological coupling.

Hippocampal Adult Neurogenesis Is Maintained by Neil3-Dependent Repair of Oxidative DNA Lesions in Neural Progenitor Cells

Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance.

PtenDeletion in Adult Hippocampal Neural Stem/Progenitor Cells Causes Cellular Abnormalities and Alters Neurogenesis

Adult neurogenesis persists throughout life in restricted brain regions in mammals and is affected by various physiological and pathological conditions. The tumor suppressor gene Pten is involved in adult neurogenesis and is mutated in a subset of autism patients with macrocephaly; however, the link between the role of PTEN in adult neurogenesis and the etiology of autism has not been studied before. Moreover, the role of hippocampus, one of the brain regions where adult neurogenesis occurs, in development of autism is not clear. Here, we show that ablating Pten in adult neural stem cells in the subgranular zone of hippocampal dentate gyrus results in higher proliferation rate and accelerated differentiation of the stem/progenitor cells, leading to depletion of the neural stem cell pool and increased differentiation toward the astrocytic lineage at later stages. Pten-deleted stem/progenitor cells develop into hypertrophied neurons with abnormal polarity. Additionally, Pten mutant mice have macrocephaly and exhibit impairment in social interactions and seizure activity. Our data reveal a novel function for PTEN in adult hippocampal neurogenesis and indicate a role in the pathogenesis of abnormal social behaviors.

Contextual learning increases dendrite complexity and EphrinB2 levels in hippocampal mouse neurons

Although the role of hippocampus in memory processing is well assessed, an association of experience-dependent behavioural modifications with hippocampal neuron morphological and biochemical changes deserves further characterisation. Here, we present evidence of dendritic alterations together with rapid accumulation of EphrinB2, a factor known to influence cell plasticity, in pyramidal neurons of the CA1 area of mouse hippocampus, during the formation of recent contextual fear memory. Male C57BL/6N mice exhibited a robust fear response 24 h after contextual and cued fear conditioning. At this time and in the absence of the memory test, conditioned mice showed morphological alterations in hippocampal and lateral amygdala neurons. Western blot analysis of extracts from conditioned but not pseudoconditioned or naive mice showed a specific increase in the amount of EphrinB2 in the hippocampus but not the cortex. However, levels of EphA4 receptor, known to interact trans-synaptically with EphrinB2, did not change upon conditioning in extracts from the same structures. Finally, immunohistochemical analysis of the hippocampus and amygdala of conditioned mice showed increased levels of EphrinB2 in pyramidal neurons of the CA1 area, when compared to pseudoconditioned and control mice. Such increase was not observed in other hippocampal areas or the amygdala. These results suggest that rapid accumulation of EphrinB2 in hippocampal CA1 neurons is involved in the behavioural and cellular modifications induced by contextual fear conditioning. A similar mechanism does not appear to occur in lateral amygdala neurons, in spite of the robust behavioural and cellular modifications induced in such structure by cued fear conditioning.

Increased hippocampal tau phosphorylation and axonal mitochondrial transport in a mouse model of chronic stress

Corticotropin-releasing hormone (CRH) is considered the driving force of the hypothalamo-pituitary-adrenal (HPA) axis and plays an important role in mood regulation. The HPA axis is reported to be closely related to acute stress-induced tau phosphorylation in the rodent hippocampus. However, the relationship between the hyperactive HPA axis and tau phosphorylation in the hippocampus and hence the functional implications for chronic stress are not fully understood. In this study, we aimed to examine tau phosphorylation and the effect on axonal transport of mitochondria in the hippocampus of a chronic stress model. A mouse model was created by neonatal isolation before weaning, followed by chronic mild stress by social isolation after weaning. Behavioural tests showed that the model had a typical depression/anxiety-like behaviour accompanied by increased plasma corticosterone level and hypothalamic CRH mRNA expression. Phosphorylated tau increased significantly, accompanied by increased synaptosomal mitochondrial levels in hippocampus of the chronic stress model. CRH receptor 1 antagonist (CP154,526) treatment, not glucocorticoid receptor antagonist (RU486) treatment, decreased tau phosphorylation and synaptosomal mitochondrial levels in the hippocampus of the mouse model. Consistent with an in-vivo model, when hyperphosphorylated tau was inhibited by lithium in cultured primary hippocampal neurons, mitochondrial transport monitored by live imaging was also decreased. We show here for the first time that phosphorylated tau in the hippocampus of a chronic stress model, accompanied by increased mitochondrial transport, was mediated by CRH receptor 1, not by glucocorticoid receptors, which suggests that centrally derived CRH may be involved in the process of mitochondrial axon transport and hence play an important role in hippocampus of a chronic stress model.

Monoamine deficits in the brain of methyl-CpG binding protein 2 null mice suggest the involvement of the cerebral cortex in early stages of Rett syndrome

Rett syndrome is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 gene (MECP2). Several neural systems are affected in Rett, resulting in an autonomic dysfunction, a movement disorder with characteristic loss of locomotor abilities and profound cognitive impairments. A deregulation of monoamines has been detected in the brain and cerebrospinal fluid of both Rett patients and a Rett syndrome murine model, the Mecp2 knock-out mouse. Our goal was to characterize the onset and progression of motor dysfunction in Mecp2tm1.1Bird knock-out mice and the possible neurochemical alterations in different brain regions potentially playing a role in Rett-like pathophysiology, at two different time-points, at weaning (3 weeks old) and in young adults when overt symptoms are observed (8 weeks old). Our results revealed significant age- and region-dependent impairments in these modulatory neurotransmitter systems that correspond well with the motor phenotype observed in these mice. At 3 weeks of age, male Mecp2 knock-out mice exhibited ataxia and delayed motor initiation. At this stage, noradrenergic and serotonergic transmission was mainly altered in the prefrontal and motor cortices, whereas during disease progression the neurochemical changes were also observed in hippocampus and cerebellum. Our data suggest that the deregulation of norepinephrine and serotonin systems in brain regions that participate in motor control are involved in the pathophysiology of Rett syndrome motor phenotypes. Moreover, we highlight the contribution of cortical regions along with the brainstem to be in the origin of the pathology and the role of hippocampus and cerebellum in the progression of the disease rather than in its establishment.

Voluntary exercise and palatable high-fat diet both improve behavioural profile and stress responses in male rats exposed to early life stress: Role of hippocampus

Childhood trauma induced by adverse early life experience is associated with increased risk of psychological disorders in adulthood. Disruption of normal development has been shown to affect hippocampal morphology and function, influencing adaptations to stress. Here we investigated whether palatable food and/or exercise would ameliorate the behavioural responses following early life stress in rats. Rats were subjected to 15 (S15) or 180 (S180) minutes separation from dams on postnatal days 2-14. After weaning, rats were assigned to either receive chow (C), high-fat diet (HFD), voluntary exercise (running, R), or combined HFD and R for 11 weeks. In addition to anxiety- and depression-like behaviours, response to restraint stress was measured. Glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5HT1A) receptor mRNA in the hippocampus were measured. S180 rats had similar body weight to S15, however their plasma insulin concentrations were double those of S15 rats when consuming HFD; adding exercise reduced plasma insulin. Anxiety-like behaviour in S180 rats, measured using Light Dark test (LDT) and Elevated Plus Maze (EPM) were ameliorated by the provision of HFD, R or HFD+R. A similar effect was observed on depression-like behaviour assessed by forced swim test (FST), with less time being spent immobile. Exposure to early-life stress during development was associated with significant reductions in hippocampal GR, 5HT1A receptor and BDNF mRNA, and these changes were normalized in S180 rats provided with HFD or exercise. Prolonged maternal separation resulted in exacerbated hyperinsulinemia when consuming HFD suggesting that these rats are metabolically disadvantaged. In summary, voluntary exercise alone or in combination with HFD produced beneficial effects on both behaviour and metabolic outcomes in rats exposed to early life stress.

Impaired neurogenesis is an early event in the etiology of familial Alzheimer's disease in transgenic mice.

Formation of new neurons in the adult brain takes place in the subventricular zone and in the subgranule layer of the dentate gyrus throughout life. Neurogenesis is thought to play a role in hippocampus- and olfaction-dependent learning and memory. However, whether impairments in neurogenesis take place in learning and memory disorders, such as Alzheimer's disease, is yet to be established. Importantly, it remains to be elucidated whether neurogenic impairments play a role in the course of the disease or are the result of extensive neuropathology. We now report that transgenic mice harboring familial Alzheimer's disease-linked mutant APPswe/PS1DeltaE9 exhibit severe impairments in neurogenesis that are evident as early as 2 months of age. These mice exhibit a significant reduction in the proliferation of neural progenitor cells and their neuronal differentiation. Interestingly, levels of hyperphosphorylated tau, the cytotoxic precursor of the Alzheimer's disease hallmark neurofibrillary tangles, are particularly high in the neurogenic niches. Isolation of neural progenitor cells in culture reveals that APPswe/PS1DeltaE9-expressing neurospheres exhibit impaired proliferation and tau hyperphosphorylation compared with wildtype neurospheres isolated from nontransgenic littermates. This study suggests that impaired neurogenesis is an early critical event in the course of Alzheimer's disease that may underlie memory impairments, at least in part, and exacerbate neuronal vulnerability in the hippocampal formation and olfaction circuits. Furthermore, impaired neurogenesis is the result of both intrinsic pathology in neural progenitor cells and extrinsic neuropathology in the neurogenic niches. Finally, hyperphosphorylation of the microtubule-associated protein tau, a critical player in cell proliferation, neuronal maturation, and axonal transport, is a major contributor to impaired neurogenesis in Alzheimer's disease.

Role of the hippocampus in goal-oriented tasks requiring retrieval of spatial versus non-spatial information

The role of the hippocampus in non-spatial memory has been issue of some controversy. To investigate the nature of dorsal hippocampus engagement in spatial and non-spatial memory we performed discrete excitotoxic lesions of this region before mice (C57/BL6) were trained in one of two tasks that required the animals to retrieve a hidden food reward. In the visuospatial task animals had to remember a particular spatial location, independent of odor cues. In contrast, in a non-spatial olfactory task animals had to remember a particular odor, independent of spatial location. The mice were trained in one of these tasks over a period of three days. We found that lesions restricted to the dorsal hippocampus affected performance only in the spatial task. In contrast, lesions that also encompassed a larger portion of the ventral hippocampus caused a moderate deficit in the olfactory task. These results are consistent with the role of the dorsal hippocampus in long-term spatial episodic memory, and support the involvement of larger portions of the hippocampus on the encoding of non-spatial olfactory representations.

The role of the hippocampus in mnemonic integration and retrieval: complementary evidence from lesion and inactivation studies

Two forms of account have been proposed for how animals form integrated memories for patterns of stimulation: the elemental account holds that the elements that make up the pattern become directly linked to one another, whereas the configural account holds that these elements become bound together through their capacity to activate a separate, shared configural memory. The hippocampus and perirhinal cortex have been linked to both elemental and configural processes. Here, we assessed the role of the rat hippocampus and perirhinal cortex in these distinct ways of processing patterns of sensory stimulation involving auditory, visual context and temporal information. Using selective lesions and inactivation techniques we identified a specific role for the hippocampus in the retrieval of configural memories but not of those that could be encoded elementally; we also identified a role for the rat perirhinal cortex in visual contextual learning. These results, using a novel combination of behavioural assays, provide clear support for the view that patterns of stimulation can be encoded either elementally or configurally, and that disruption of hippocampal function leaves rats reliant on elemental processes.

S.23.02 Role of hippocampus in the cognitive control of anxiety

S.23.02 Role of hippocampus in the cognitive control of anxiety

Motivated exploratory behaviour in the rat: The role of hippocampus and the histaminergic neurotransmission

Exploration is one of most basic adaptive behavioural responses, giving the animal an important evolutionary advantage to survive in a changing environment. Inspection of novel environments might be come with motivated exploratory behaviour. In spite that this type of exploration in the rat is known for many years, little attention has been given to the intrinsic mechanisms or the brain structures that are involved in. In the present work the hippocampus, the neurotransmitter histamine, and the geometrical features of novel objects were examined in a model of conflictive and non-conflictive exploration in the rat which evaluates incentive-motivated exploration. Young adult intact rats were tested in a neutral non-conflictive behavioural activity detector (OVM), with (eOVM) or without (sOVM) novel objects. Three different objects were used: a box, a toy duck, and a tower. Results show that animals decrease its general motor activity (horizontal, ambulatory and non-ambulatory activity) in favor to exploration of the objects. Motivated exploration was not the same for all three objects. Rats explored significantly more the Tower and the Box objects than the Duck item. Behavioral patterns of hippocampus-implanted rats showed decreased scores in motor activity but maintained the difference in the relation of “without/with objects” exploration. When hippocampus-implanted rats were tested in a conflictive exploration device (the elevated asymmetric plus-maze), exploration of the No Wall arm, considered the most fear-inducing environment, was significantly more explored by the animal when the tower object was positioned at its end than when it was absent. Microinjection into the ventral hippocampus of histamine abolished this motivated exploratory response. Pre-treatment with pyrilamine, and not with ranitidine, was effective to block the inhibitory effect of histamine on the object motivated exploration. Results confirm that the hippocampus is involved on incentive motivated exploration, and suggest that histamine is part of an analyzing neuronal circuit of novelty incentivating behavioural responses in rats.