Modulation of hippocampus-prefrontal cortex synaptic transmission and disruption of executive cognitive functions by MK-801.

Noncompetitive N-methyl-d-aspartate receptor antagonists such as phencyclidine and MK-801 are known to impair cognitive function in rodents and humans, and serve as a useful tool to study the cellular basis for pathogenesis of schizophrenia cognitive symptoms. In the present study, we tested in rats the effect of MK-801 on ventral hippocampus (HPC)-medial prefrontal cortex (mPFC) synaptic transmission and the performance in 2 cognitive tasks. We found that single injection of MK-801 (0.1 mg/kg) induced gradual and long-lasting increases of the HPC-mPFC response, which shares the common expression mechanisms with long-term potentiation (LTP). But unlike LTP, its induction required no enhanced or synchronized synaptic inputs, suggesting aberrant characteristics. In parallel, rats injected with MK-801 showed impairments of mPFC-dependent cognitive flexibility and HPC-mPFC pathway-dependent spatial working memory. The effects of MK-801 on HPC-mPFC responses and spatial working memory decayed in parallel within 24 h. Moreover, the therapeutically important subtype 2/3 metabotropic glutamate receptor agonist LY379268, which blocked MK-801-induced potentiation, ameliorated the MK-801-induced impairment of spatial working memory. Our results show a novel form of use-independent long-lasting potentiation in HPC-mPFC pathway induced by MK-801, which is associated with impairment of HPC-mPFC projection-dependent cognitive function.

Amygdala responses to quetiapine XR and citalopram treatment in major depression: the role of 5-HTTLPR-S/Lg polymorphisms.

OBJECTIVES: Genotype and drug pharmacology may contribute to variations in brain response to antidepressants. We examined the impact of two antidepressants with differential actions on serotonin transporter and the 5-HHTLPR-S/Lg polymorphisms on amygdala responses in major depressive disorder (MDD). METHODS: Caucasians with MDD were given either citalopram or quetiapine extended release for 8 weeks. Patients were genotyped for 5-HTTLPR. Clinical efficacy was assessed using the Hamilton Depression Rating Scale. fMRI responses to negative emotional faces were acquired at baseline, week 1 and week 8. The outcome measure was change in amygdala responses at week 8. RESULTS: Citalopram had no effect on amygdala responses in MDD patients with S/Lg alleles at weeks 1 and 8 compared with baseline, whereas it induced changes in amygdala responses in LL homozygotes. By contrast, quetiapine decreased amygdala responses at both time points in S/Lg carriers, and changes in amygdala responses at week 8 correlated with a reduction in depression scores. The small number of LL homozygotes in quetiapine group was a limitation. Efficacy of both treatments was comparable. CONCLUSIONS: These preliminary data suggest that pharmacological mechanisms and genetics need to be considered in the development of neuroimaging markers for the evaluation of antidepressant treatments.

Corpus callosal morphology in youth with bipolar depression.

OBJECTIVES: Recent evidence has demonstrated that corpus callosum maturation follows a similar developmental timeline to cognitive processes. Bipolar disorder (BD) has been associated with disruptions in error processing, response inhibition, and motor functioning, which are mediated by underlying white matter structures, including the corpus callosum. Disruptions in white matter integrity have been demonstrated in BD. However, it is unknown whether alterations in the developmental trajectory of the corpus callosum may contribute to cognitive impairments in the disorder. METHODS: We assessed the area of the corpus callosum and its subregions (the genu, rostral body, anterior and posterior bodies, isthmus, and splenium) in 14 treatment-naïve adolescents with BD (<21 years of age and in the depressed phase) and 18 healthy adolescent controls. RESULTS: In comparison with healthy controls, participants with BD demonstrated a significantly reduced overall corpus callosum area. We also noted smaller areas in the anterior and posterior mid-body of the corpus callosum in adolescents with BD. CONCLUSIONS: Our results suggest that commissural fibers of the corpus callosum are disrupted in early-onset BD. Specific decreases in the anterior and posterior mid-body callosal aspects may contribute to motor organization and inhibition deficits seen in BD. These findings are consistent with the involvement of inter-hemispheric tracts in early-onset BD, which may reflect an early deviation in white matter development.

Passive spatial perception facilitates the expression of persistent hippocampal long-term depression.

Learning-facilitated plasticity describes the ability of hippocampal synapses to respond with synaptic plasticity when weak afferent stimulation is coupled with a spatial learning event. Qualitative differences appear to influence whether long-term potentiation or long-term depression (LTD) are facilitated by spatial learning. At many hippocampal synapses, LTD is facilitated when rats actively explore a novel spatial context. We investigated whether learning-facilitated plasticity is expressed when an unconstrained but stationary rat observes a computer-generated spatial environment. Visual fields were separated. Novel object configurations were presented to one field; familiar constellations were presented to the other field. LTD was facilitated in the CA1 region of the hemisphere to which novel object constellations were presented. Familiar constellations had no effect. LTD facilitation was prevented by treatment with the protein translation inhibitor, anisomycin. LTD in the dentate gyrus was not facilitated by novel object constellations, suggesting that effects are not common to all hippocampal subfields. These data support a unique association of LTD in the CA1 region with learning about spatial context and indicate that rats can passively perceive space.

Postpartum hypertensive disorders in the Emergency Department - A retrospective review of local practice in Calgary, Alberta.

Hypertensive disorders of pregnancy (HDP) commonly occur postpartum and are associated with preventable maternal morbidity and mortality. HDP is the most common reason for presentation to the Emergency Department (ED) after delivery. However, given the broad range of non-specific symptoms, recognition and management of postpartum HDP may be delayed leading to serious adverse clinical outcomes. OBJECTIVES: To describe: (1) the clinical presentation; (2) ED physician's diagnosis; and (3) current ED management of women with HDP in Calgary ED's. METHODS: A retrospective review of postpartum women (within 42 days of delivery) attending three Calgary EDs between 2011 and 2012 was performed. Administrative data was used to randomly select 119 women; 44 with diagnostic codes for any HDP (labeled "HDP") and 75 with diagnostic codes for related diagnoses (e.g., abdominal pain, headache) (labeled "non-HDP"). Charts were reviewed for: maternal demographics; obstetrical history; and ED clinical findings, investigations and management. RESULTS: Maternal characteristics were similar between groups. There was considerable overlap in clinical presentation between groups, with no significant difference for any presenting symptom. Only 52.3% (CI 40.0-64.3%) of women in the "HDP" group had HDP investigations (bloodwork and urinalysis) vs. 30.4% (CI 18.7-58.5%) of "non-HDP" (p = 0.072). HDP was diagnosed by the ED team in 42.9% (CI 31.1-55.5%) of the HDP group of whom only 40.3% (CI 28.7-53.1) received antihypertensive therapy. CONCLUSIONS: Postpartum HDP is commonly under-recognized and under-treated in the ED, highlighting opportunities for interventions to improve the recognition and management of postpartum HDP.

Perspectives of Patients and Professionals on Information and Education After Myocardial Infarction With Insight for Mixed Reality Implementation: Cross-Sectional Interview Study.

BACKGROUND: Patient education is crucial in the secondary prevention of cardiovascular disease. Novel technologies such as augmented reality or mixed reality expand the possibilities for providing visual support in this process. Mixed reality creates interactive digital three-dimensional (3D) projections overlaying virtual objects on the real-world environment. While augmented reality only overlays objects, mixed reality not just overlays but anchors virtual objects to the real world. However, research on this technology in the patient domain is scarce. OBJECTIVE: The aim of this study was to understand how patients perceive information provided after myocardial infarction and examine if mixed reality can be supportive in this process. METHODS: In total, 12 patients that experienced myocardial infarction and 6 health care professionals were enrolled in the study. Clinical, demographic, and qualitative data were obtained through semistructured interviews, with a main focus on patient experiences within the hospital and the knowledge they gained about their disease. These data were then used to map a susceptible timeframe to identify how mixed reality can contribute to patient information and education. RESULTS: Knowledge transfer after myocardial infarction was perceived by patients as too extensive, not personal, and inconsistent. Notably, knowledge on anatomy and medication was minimal and was not recognized as crucial by patients, whereas professionals stated the opposite. Patient journey analysis indicated the following four critical phases of knowledge transfer: at hospital discharge, at the first outpatient visit, during rehabilitation, and during all follow-up outpatient visits. Important patient goals were understanding the event in relation to daily life and its implications on resuming daily life. During follow-up, understanding physical limitations and coping with the condition and medication side effects in daily life emerged as the most important patient goals. The professionals' goals were to improve recovery, enhance medication adherence, and offer coping support. CONCLUSIONS: There is a remarkable difference between patients' and professionals' goals regarding information and education after myocardial infarction. Mixed reality may be a practical tool to unite perspectives of patients and professionals on the disease in a more even manner, and thus optimize knowledge transfer after myocardial infarction. Improving medication knowledge seems to be a feasible target for mixed reality. However, further research is needed to create durable methods for education on medication through mixed reality interventions.

Hippocampal long-term depression: master or minion in declarative memory processes?

The neural mechanisms for the formation of declarative memory (memory for facts and events) are believed to be integrated from processes mediated by hippocampal long-term potentiation (LTP) and long-term depression (LTD). Traditionally, LTP has been designated as the main mediator of spatial memory storage in the hippocampus, whereas LTD has been assigned an auxiliary role in signal-to-noise regulation or in forgetting. It has recently become apparent, however, that LTD contributes directly to hippocampal information storage. In fact, LTD could dominate in the processing of precise spatial characteristics. Accumulating evidence supports the idea that LTP and LTD enable distinct and separate forms of information storage, which together facilitate the generation of a spatial cognitive map.

The hippocampal CA1 region and dentate gyrus differentiate between environmental and spatial feature encoding through long-term depression.

Novel spatial information is encoded in the hippocampus by plastic changes of synaptic properties. Novel space consists of several types of information that may evoke differential synaptic responses in individual hippocampal subregions. To examine this possibility, we recorded field potentials from the dentate gyrus (DG) and CA1 region in freely moving adult rats. Stimulation protocols that were marginally subthreshold for the induction of persistent long-term potentiation (LTP) or long-term depression (LTD) were implemented, concurrent with exposure to novel spatial information. We found that in both hippocampal subregions, exploration of a novel empty hole board facilitated LTP. However, LTD facilitation was subregion specific and dependent on the nature of the cues. In the CA1 region, partially concealed cues had a facilitatory effect on LTD. LTD in the DG was facilitated by large directional cues. Thus, although LTP was facilitated uniformly in both areas by the same novel environment, LTD was facilitated in a region-specific manner, based on the nature of the cue. This implies that spatial changes within an environment elicit local changes of synaptic weights dependent on the type of information and, hence, generate a complete cognitive map as a consequence of cooperation of synaptic plasticity in all participating subregions.

Beta-adrenoreceptors comprise a critical element in learning-facilitated long-term plasticity.

A novel spatial environment consists of several different types of information that may be encoded by cellular information storage mechanisms such as long-term potentiation (LTP) and long-term depression (LTD). Arousal, mediated, for example, by activation of the noradrenergic system, is a critical factor in information acquisition and may enhance the encoding of novel spatial information. Using electrophysiological recordings of hippocampal responses in freely moving rats during spatial learning, we investigated the role of the beta-adrenoreceptor in Schaeffer collateral-CA1 synaptic plasticity. We found that novel exploration of spatial context facilitates induction of LTD that is inhibited by intracerebroventricular application of the beta-adrenoreceptor antagonist, propranolol. Long-lasting homosynaptic LTD, that was electrically induced by low-frequency stimulation, was unaffected by the antagonist. Although application of a beta-adrenoreceptor agonist (isoproterenol) did not affect electrically induced LTD, agonist application facilitated short-term depression (STD) into LTD and mimicked the augmentation, through spatial exploration, of STD into LTD. Exploration of a novel empty environment facilitated LTP that was prevented by application of propranolol. These results suggest that beta-adrenoreceptors may facilitate encoding of spatial information through synaptic plasticity in the hippocampus and that noradrenaline is a key factor in effective information acquisition.

The impact of age of onset on amygdala intrinsic connectivity in major depression.

BACKGROUND: Early-onset major depressive disorder (EO-MDD), beginning during childhood and adolescence, is associated with more illness burden and a worse prognosis than adult-onset MDD (AO-MDD), but little is known about the neural features distinguishing these subgroup phenotypes. Functional abnormalities of the amygdala are central to major depressive disorder (MDD) neurobiology; therefore, we examined whether amygdala intrinsic connectivity (IC) can differentiate EO-MDD from AO-MDD in a cohort of adult MDD patients. SUBJECTS AND METHODS: Twenty-one EO-MDD (age of onset ≤18 years), 31 AO-MDD patients (age of onset ≥19 years), and 19 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (7 minutes). Amygdala seed-based resting-state functional connectivity was compared between groups. RESULTS: AO-MDD patients showed loss of inverse left amygdala-left dorsolateral prefrontal cortex IC and increased inverse left amygdala-left inferior parietal IC, compared to both HCs and EO-MDD. EO-MDD showed a switch from inverse to positive IC with right dorsomedial prefrontal cortex, compared to HCs and AO-MDD. This effect was removed when we controlled for illness burden. CONCLUSION: Alterations in amygdala IC with the default-mode network were specifically related to EO-MDD, whereas amygdala IC with executive cognitive control regions was preferentially disrupted in AO-MDD. Increased illness burden, an important clinical marker of EO-MDD, accounted for its specific effects on amygdala IC. Brain imaging has the potential for validation of clinical subtypes and can provide markers of prognostic value in MDD patients.

Effect of phosphate functional groups on the calcification capacity of acrylic hydrogels.

The incorporation of negatively charged groups into the structure of synthetic polymers is frequently advocated as a method for enhancing their calcification capacity required in orthopedic and dental applications. However, the results reported by various research groups are rather contentious, since inhibitory effects have also been observed in some studies. In the present study, phosphate groups were introduced in poly(2-hydroxyethyl methacrylate) (PHEMA) by copolymerization with 10% mol of either mono(2-acryloyloxyethyl) phosphate (MAEP) or mono(2-methacryloyloxyethyl) phosphate (MMEP). Incubation of these hydrogels for determined durations (1-9 weeks) in a simulated body fluid (SBF) solution induced deposition of calcium phosphate (CaP) deposits of whitlockite type. After 9 weeks, the amount of calcium deposited on the phosphate-containing polymers was four times lower than that found on PHEMA, as determined by X-ray photoelectron spectroscopy (XPS). Samples of copolymer HEMA-MAEP were implanted subcutaneously in rats and evaluated after 9 weeks. No CaP deposits could be detected on the copolymer by XPS or energy dispersive X-ray spectroscopy, while PHEMA samples were massively calcified. It was concluded that the presence of phosphate groups decreased the calcification capacity of the hydrogels, and that in the conditions of this study, the phosphate groups had an inhibitory effect on the deposition of CaP phases on HEMA-based hydrogels.

High resolution transmission electron microscopy of developing enamel in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi).

The permanent tooth plates of the Australian lungfish, Neoceratodus forsteri, are covered by enamel that develops initially in a similar manner to that of other vertebrates. As the enamel layer matures, it acquires several unusual characteristics. It has radially oriented protoprismatic structures with the long axes of the protoprisms perpendicular to the enamel surface. Protoprisms can be defined as aggregations of hydroxyapatite crystals that lack the highly ordered arrangement of the rods of mammalian enamel but are not without a specific structure of their own. The protoprisms are arranged in layers of variable thickness that are deposited sequentially as the tooth plate grows. They may be confined to the separate layers, or may cross the boundary between each layer. Crystals within the protoprisms are long and thin with hydroxyapatite c-axis dimensions of between 30 and 350 nm, and with typical a-b axis dimensions of 5-10 nm. The hydroxyapatite crystals of lungfish enamel have no centre dark lines of octacalcium phosphate, an unusual character among vertebrates. As each crystal develops, arrays of atoms may change direction, and regions exist where dislocations and extra lattice planes are inserted into the long crystal. The resulting hydroxyapatite crystal is not straight, and has a rough surface. The crystals are arranged in tangled structures with their crystallographic c-axes closely aligned with the long axis of the protoprism. Lungfish enamel differs from the enamel of higher vertebrates in that the hydroxyapatite crystals are of different shape, and, in mature enamel, the protoprisms remain as protoprisms and do not develop into the conventional prismatic structures characteristic of mammalian enamel.

Inferring parrotfish (Teleostei: Scaridae) pharyngeal mill function from dental morphology, wear, and microstructure.

Morphology, occlusal surface topography, macrowear, and microwear features of parrotfish pharyngeal teeth were investigated to relate microstructural characteristics to the function of the pharyngeal mill using scanning electron microscopy of whole and sectioned pharyngeal jaws and teeth. Pharyngeal tooth migration is anterior in the lower jaw (fifth ceratobranchial) and posterior in the upper jaw (paired third pharyngobranchials), making the interaction of occlusal surfaces and wear-generating forces complex. The extent of wear can be used to define three regions through which teeth migrate: a region containing newly erupted teeth showing little or no wear; a midregion in which the apical enameloid is swiftly worn; and a region containing teeth with only basal enameloid remaining, which shows low to moderate wear. The shape of the occlusal surface alters as the teeth progress along the pharyngeal jaw, generating conditions that appear suited to the reduction of coral particles. It is likely that the interaction between these particles and algal cells during the process of the rendering of the former is responsible for the rupture of the latter, with the consequent liberation of cell contents from which parrotfish obtain their nutrients.

Prismatic dentine in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi).

The Australian lungfish, Neoceratodus forsteri, has a dentition consisting of enamel, mantle dentine and bone, enclosing circumdenteonal, core and interdenteonal dentines. Branching processes from cells that produce interdenteonal dentine leave the cell surface at different angles, with collagen fibrils aligned parallel to the long axis of each process. In the interdenteonal dentine, crystals of calcium hydroxyapatite form within fibrils of collagen, and grow within a matrix of non-collagenous protein. Crystals are aligned parallel to the cell process, as are the original collagen fibrils. Because the processes are angled to the cell surface, the crystals within the core or interdenteonal dentine are arranged in bundles set at angles to each other. Apatite crystals in circumdenteonal dentine are finer and denser than those of the interdenteonal dentine, and form outside the fibrils of collagen. In mature circumdenteonal dentine the crystals of circumdenteonal dentine form a dense tangled mass, linked to interdenteonal dentine by isolated crystals. The functional lungfish tooth plate contains prisms of large apatite crystals in the interdenteonal dentine and masses of fine tangled crystals around each denteon. This confers mechanical strength on a structure with little enamel that is subjected to heavy wear.

Scale structure in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi).

Scales of the Australian lungfish, Neoceratodus forsteri, are secreted within the dermis by a capsule of scleroblasts, and enclosed in a pouch made of collagen fibers, in contact with the epidermis over the posterior third of the scale. Each scale grows from a focus, which represents the first formed part of the scale. On the internal surface of the scale is elasmodin, made of collagen fiber bundles arranged in layers. Elasmodin, unmineralized in N. forsteri, contains cells in the living animal, and the number of layers increases as the scales grow. Squamulin, on the thin external part of the scale, is also laid down in layers, and based on a matrix of fine collagen fibrils, mineralized with a poorly crystalline biogenic calcium hydroxylapatite. Squamulin is divided into separate sections called squamulae, and contains long tubules with cells applied to the wall of the tubule. The anterior and lateral surfaces of the squamulin are ornamented with pediculae, and the posterior surface has longitudinal ridges, from which collagen fibers extend to anchor the scale within the pouch. Elasmodin and squamulin are linked by unmineralized collagen fibrils. The layers, formed at irregular intervals, are connected around the margin of the scale, effectively converting the whole scale into a flat structure resembling a pearl, with the first formed tissues deeply embedded inside the scale, and the youngest on the outer surface. Incremental lines in the hard tissue, and the number of layers in the elasmodin, do not reflect the chronological age of the fish.

Differential effects of mGluR1 and mGlur5 antagonism on spatial learning in rats.

The effects of selective mGluR1 and mGluR5 antagonists on long-term acquisition were tested in a spatial three-choice reward-finding test. Bilateral prelimbic injections of the mGluR1 antagonist, (S)-4-carboxyphenylglycine (4-CPG), before training sessions blocked acquisition of correct performance between sessions. Similar injections given after full training of a control group significantly impaired correct performance without causing a complete block. Pretraining injections (intraperitoneal or intravenous) of the systemically active mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), had no effect on long-term acquisition in the reward-finding task. In an open-field test, bilateral prelimbic pretest application of 4-CPG prevented normal adaptation of spontaneous exploration as seen in control animals. MPEP, on the other hand, had no effect. In conclusion, the results confirmed that mGluR1 is involved in spatial long-term acquisition and suggested an additional role in recall of acquired skills. Furthermore, it was concluded that antagonism of mGluR1 or mGluR5 had different effects both in the appetitive spatial task and in the open-field test.

Ultrastructure of developing tooth plates in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi).

While the lungfish dentition is partially understood as far as morphology and light microscopic structure is concerned, the ultrastructure is not. Each tooth plate is associated with a dental lamina that develops from the inner layer of endodermal cells that form the oral epithelium. Dentines, bone and cartilage of the jaws differentiate from mesenchyme cells aggregating beneath the oral endothelium. Enamel, in the developing and in the mature form, has similarities to that of other early vertebrates, but unusual characters appear as development proceeds. Ameloblasts are capable of secreting enamel, and, with mononuclear osteoclasts, of remodelling the bone below the tooth plate. The forms of dentine, all based largely on an extracellular matrix of collagen and mineralised with biological apatite, differ from each other and from the underlying bone in the ultrastructure of associated cells and in the mineralised extracellular matrices produced. Cell processes emerging from the odontoblasts and from the osteoblasts vary in length, degree of branching and of anastomoses between the processes, although all of the cell types have large amounts of rough endoplasmic reticulum. Mineralisation of the extracellular matrices varies among the enamel, dentines and bone in the tooth plate. In addition, the development of the hard tissues of the tooth plates indicates that many of the similarities in fine structure of the dentition in lungfish, to tissues in other fish and amphibia, apparent early in development, disappear as the dentition matures.

Anomalies in the developing neural and visceral head skeleton of the Australian lungfish, Neoceratodus forsteri.

Several anomalies occur in the developing neural and visceral head skeleton of young specimens of Neoceratodus forsteri that have been reared under laboratory conditions. These include anomalies of the basicranium and its derivatives, aberrations of the anterior mandible and hyoid apparatus, and abnormalities in the articulation of the jaws and the elements that produce them. Apart from the occasional absence of the basihyal, and failure of the quadrate processes to form, the anomalies are not deficiencies. Most involve malformations of parts of the neurocranium and visceral skeleton, inappropriate articulations or fusions between elements, disunity in structures that are normally fused and the appearance of supernumerary elements. The incidence of chondral anomalies, generally higher than aberrations that occur in the dermal skeleton in juvenile lungfish, ranges from 1-10% in laboratory reared individuals that have not been subjected to experimental interference. The anomalies differ from those found in many amphibian populations, in the field and in the laboratory, because they involve the cranium, and not the limbs, and the lungfish have not been exposed to the factors that cause anomalies in the amphibians. It is unlikely that the existence of those anomalies, if it is reflected in the wild population, places a selective pressure on the lungfish, because, in a normal season, less than 1% of the total number of eggs produced survive to be recruited into the adult population.

Cartilage, bone, and intermandibular connective tissue in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi).

The connective tissue that links the bones of the mandible in the Australian lungfish, Neoceratodus forsteri, has been described as an intermandibular cartilage, and as such has been considered important for phylogenetic analyses among lower vertebrates. However, light and electron microscopy of developing lungfish jaws demonstrates that the intermandibular tissue, like the connective tissue that links the bones of the upper jaw, contains fibroblasts and numerous bundles of collagen fibrils, extending from the trabeculae of the bones supporting the tooth plates. It differs significantly in structure and in staining reactions from the cartilage and the bone found in this species. In common with the cladistian Polypterus and with actinopterygians and some amphibians, lungfish have no intermandibular cartilage. The connective tissue linking the mandibular bones has no phylogenetic significance for systematic grouping of lungfish, as it is present in a range of different groups among lower vertebrates.

Learning-facilitated long-term depression requires activation of the immediate early gene, c-fos, and is transcription dependent.

De novo gene transcription is a prerequisite for long-term information storage in the brain. Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with long-lasting synaptic plasticity to the coupling of afferent stimulation with a spatial learning experience. Strikingly, long-term depression (LTD) is facilitated by context-dependent spatial learning experiences suggesting it may play a role in information storage to enable spatial memory. Here, we investigated if learning-facilitated LTD requires the transcription factor, c-Fos and is transcription-dependent. Novel spatial learning about object-place configurations coupled with weak low frequency afferent stimulation induced robust LTD in control animals that persisted for >24h and was associated with elevations in hippocampal expression of c-Fos. Intracerebral application of a c-fos antisense oligonucleotide prevented the facilitation of LTD by novel spatial learning, inhibited elevations of c-Fos triggered by LTD and impaired spatial learning. The expression of the transcription factor zif268 was unaffected by the c-fos antisense oligonucleotide. Learning-facilitated LTD was prevented by a transcription inhibitor. These data support that learning-facilitated LTD requires elevations in c-Fos and is transcription dependent. The observation that LTD shares key regulatory mechanisms with learning and memory processes argues strongly for a role for this form of synaptic plasticity in long-term information storage in the hippocampus.