Rapid onset of squamous cell carcinoma in a thin skin graft donor site.

BACKGROUND: Squamous cell carcinomas are malignant tumours of epithelial origin that can appear on sites subjected to chronic inflammation after a period of several years. The rapid development of squamous cell carcinoma at the donor site for a thin skin graft is a rare and poorly understood situation. PATIENTS AND METHODS: We report the case of a patient undergoing thin skin grafting to cover the area of removal of a vertex squamous cell carcinoma and in whom squamous cell carcinoma appeared at the donor site within 9 weeks. DISCUSSION: In our case, we ruled out intraoperative contamination because two sets of surgical instruments were used. Given the number of cases reported in the literature, a chance event seems unlikely. The hypothesis of an acute inflammatory process caused by scarring of the thin skin graft site appears to us the most convincing. Development of cancer at the graft donor site may thus be added to the list of complications of thin skin grafting.

[External canthus reconstruction with tarso-conjunctival transposition flap and Hübner's graft]. / Reconstruction du canthus externe par lambeaux de transposition tarso-conjonctivaux et greffons de Hübner.

The external canthus defects with resection of the superior and inferior eyelids external portion remains difficult to treat. The reconstruction has to focus on both the reconstruction of the tarso-conjunctival plan and the musculo-cutaneous plan but has also to treat the disappearance of the external canthus. Usually the tarso-conjunctival plan is reconstructed by a septal transplant, conqual or of palatine mucous membrane. The technique presented here suggests to use two tarso-conjunctival transposition flaps to reconstruct the external canthus and the canthal external ligament. The palpebral defect is then pulled medialy, and is easily reconstructed by a Hübner's graft. The coverage of these tarso-conjunctival flaps and grafts is realized with local cutaneous or musculo-cutaneous flaps. The aim of this reconstruction is to allow a functional and aesthetic reconstruction with respected lid margins with eyelashes. Thanks to this technique, it is possible to reconstruct external canthus defects up to half of the superior and inferior eyelids.

[Cheek reconstruction]. / Reconstruction jugale.

We describe the different cheek reconstruction techniques with primary emphasis on the superficial layers. In addition to the clinical context, location and size of the lesion will be taken into account to choose the best method that will optimize the functional and aesthetic results while minimizing potential sequelae. Main evaluation criteria include absence of natural orifice deformation, scar location, skin cover quality and respect of volumes.

[Schmid-Meyer fronto-temporal flap for nasal reconstruction]. / Le lambeau fronto-temporal de Schmid-Meyer dans les reconstructions nasales.

INTRODUCTION: Many surgical techniques have already been described to repair full thickness defects of the inferior part of the nose. The Schmid-Meyer fronto-temporal flap procedure, a little known technique, is based on the old principle of autonomization of a cutaneous flap and uses a tailor-made composite cartilaginous graft placed in the temporal region. This graft is progressively detached and allows mucosal/cartilaginous/and cutaneous nasal repair. Can this technique still be used for nasal full-thickness reconstruction? PATIENTS AND METHOD: Nine cases of nasal reconstruction using this procedure were performed. The 4-steps of the operative technique were described and the results were analyzed retrospectively. RESULTS: This procedure allows, for some specific indications, excellent reconstruction of the ala, the columella or the nasal tip. In eight cases out of nine, the result was judged good or very good by both patients and physicians. In 78%, the reconstruction was performed under local anesthesia. DISCUSSION: The Schmid-Meyer flap procedure may still be used for full-thickness reconstruction of the lower third of the nose because it allows a high quality of nasal reconstruction and few scar sequels.

[The complete dorsum nasal island flap based on the superior alar artery]. / Lambeau total du dos du nez basé sur l'artère alaire supérieure.

The complete dorsal nasal aesthetic unit can be raised in a vascular island flap based on the superior alar artery, at the level of the nasalis muscle. This flap uses the vertical glabellar cutaneous laxity. It hides scars between the nasal aesthetics units and its distal rotation point allows a pure translation of the nasal skin without distortions encountered when using medial canthal rotation flaps. This local flap is reliable and had been successfully used for four patients without complications or secondary procedures. It allows large reconstructions for up to 25 mm defects leaving minimal scars. It represents an interesting alternative for the reconstruction of defects of the nasal tip or supra tip of the nose, and has also been used for alar reconstructions.

[Primitive neuroendocrine cancer of the breast. Post-traumatic discovery of a man]. / Tumeur neuroendocrine primitive du sein. Découverte post-traumatique chez un homme.

We report a primitive neuroendocrine breast tumor (NET) in a male. This situation is uncommon by its mode of discovery. We have treated a 74-year-old man with a lesion in the left areola initially considered as an organized hematoma due to a severe trauma. The ablation was performed by direct access under local anesthesia. The analysis of the piece has showed a NET of the breast due to the positivity of the neuroendocrine, cytokeratin and hormone markers. No other NET lesion was found, excluding the secondary origin of the breast tumor. Complementary therapies associated mastectomy, lymphadenectomy, hormonotherapy. Male breast cancer is rare. NET are exceptional, only a dozen of male NET is reported. These tumors affect a specific population and have a better prognosis than infiltrating ductal carcinoma. In our case, no causal link can be demonstrated between trauma and tumor microenvironment necessary for the growth of quiescent cancer cells.

[Moldable titanium mesh for chest wall reconstruction, an elegant solution about a case report]. / Reconstruction d'une pariétectomie thoracique transfixiante par grille de titane malléable, une solution élégante à propos d'un cas.

INTRODUCTION: Several surgical techniques are available for full thickness chest wall reconstruction. The choice has to be adapted to the size of the loss of tissue, its location, and must finally be accepted by the patient's. We propose a new and unpublished solution. CASE REPORT: We have in our care a 54 years-old patient suffering from a previous loss of chest wall tissue measuring 7 cm(2) due to surgical treatment of mediastinal Hodgkin's disease with sternal and costal invasion. Because of the sequelae, the goal focused on aesthetic reconstruction. Heartbeat was visible under the skin due to a loss of secondary left breast tissue from an initial treatment with absorbable Vicryl(©) mesh followed by a local skin, and glandular flap. Our choice of reconstruction consisted of inserting a moldable titanium mesh followed by 200 g implants in each breast during the same operation. We did not experience any complications and the patient is satisfied with the results. DISCUSSION: No example of reconstruction using only a moldable titanium mesh was found in the literature on chest wall reconstruction. Our elegant choice is innovative in our discipline. However, this reconstruction materiel is already part of therapy procedures in other specialized surgeries. CONCLUSION: This case report illustrates the various facets of our speciality: bring a solution at once repair, aesthetic and unique according to the request of the patient. The use of a moldable titanium mesh allows the reconstruction of stable chest wall. The small size does not present any functional difficulties, but rather unsightly sequel.

[Conchal flap with a superior pedicle to reconstruct the middle or upper third of the auricle]. / Le lambeau de conque à pédicule supérieur pour les reconstructions hélicéennes supérieures ou moyennes.

The middle or upper third of the auricle can be reconstructed with a composite chondro-cutaneous peninsular flap of the conchal part of the auricle. This peninsular flap is based on the anastomotic network between the posterior auricular and the superficial temporal artery. The authors report their experience about 24 clinical cases. Most of the cases were partial auricular amputations for squamous cell carcinoma. The surgical procedure allows a hidden cartilaginous donor site, the concha, allowing in a single operation a color- and texture-matched reconstruction. This flap represents an alternative to more complex surgical procedures, and can easily be realised under local anaesthesia.

Evaluation of Memantine in AAV-AD Rat: A Model of Late-Onset Alzheimer's Disease Predementia.

BACKGROUND: Though our understanding of Alzheimer's disease (AD) remains elusive, it is well known that the disease starts long before the first signs of dementia. This is supported by the large number of symptomatic drug failures in clinical trials and the increased trend to enroll patients at predementia stages with either mild or no cognitive symptoms. However, the design of pre-clinical studies does not follow this attitude, in particular regarding the choice of animal models, often irrelevant to mimic predementia Late Onset Alzheimer's Disease (LOAD). OBJECTIVES: We aimed to pharmacologically validate the AAV-AD rat model to evaluate preventive treatment of AD. METHODS: We evaluated an N-methyl-D-aspartate receptor antagonist, named memantine, in AAV-AD rats, an age-dependent amyloid rat model which closely mimics Alzheimer's pathology including asymptomatic and prodromal stages. Memantine was used at a clinically relevant dose (20 mg daily oral administration) from 4 (asymptomatic phase) to 10 (mild cognitive impairment phase) months of age. RESULTS: A 6-month treatment with memantine promoted a non-amyloidogenic cleavage of APP followed by a decrease in soluble Aß42. Consequently, both long-term potentiation and cognitive impairments were prevented. By contrast, the levels of hyperphosphorylated endogenous tau remained unchanged, indicating that a long-term memantine treatment is ineffective to restrain the APP processing-induced tauopathy. CONCLUSIONS: Together, our data confirm that relevant models to LOAD, such as the AAV-AD rat, can provide a framework for a better understanding of the disease and accurate assessment of preventive treatments.

[Optimized negative pressure therapy. Case report]. / Thérapie par pression négative optimisée. A propos d'un cas.

Our patient showed major abdominal cutaneous necrosis. Detersion removed the entire thickness of half of the right-hand wall of the abdomen. We are going to explain how, by combining well known procedures, we conducted this closure. This deals with a patient aged 53, with a long case history of dermatomyositis and highly debilitating sub-cutaneous calcinosis. This patient has been treated with Imurel and high doses of corticoids since 1997. In the face of the much debilitated terrain of the patient, it was not certain that a local flap or even a pediculated flap could be made to cover this loss of substance with a minimum of risk. A cutaneous extension was then envisaged using a system of Wisebands fillets. To protect the parietal plate, accelerate its growth and reduce the skin tension, we used in combination a system of foam dressing with negative pressure therapy (NPT). The optimized NPT was used for 2 weeks. The Wisebands were installed for 1 month. The treatment lasted for 50 days and required five short sessions of general anaesthesia. The histopathological interpretation revealed an EBV lymphoma. The assessment of the extension and the therapeutic treatment of the lymphoma contributed to the duration of hospitalisation and the number of general anaesthesia sessions. The synergy effect of these two associated procedures have allowed a faster skin closure; 18 months later, no complications have occurred. The wound has closed totally and the abdominal wall is solid in spite of not having resorted to a flap or separation.

A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory.

Age-associated deficits in learning and memory are closely correlated with impairments of synaptic plasticity. Analysis of N-methyl-D-aspartate receptor (NMDAr)-dependent long-term potentiation (LTP) in CA1 hippocampal slices indicates that the glial-derived neuromodulator D-serine is required for the induction of synaptic plasticity. During aging, the content of D-serine and the expression of its synthesizing enzyme serine racemase are significantly decreased in the hippocampus. Impaired LTP and NMDAr-mediated synaptic potentials in old rats are rescued by exogenous D-serine. These results highlight the critical role of glial cells and presumably astrocytes, through the availability of D-serine, in the deficits of synaptic mechanisms of learning and memory that occur in the course of aging.

Age-related alterations of GABAergic input to CA1 pyramidal neurons and its control by nicotinic acetylcholine receptors in rat hippocampus.

The aim of this study was to determine whether age-associated alterations in the GABAergic input to pyramidal neurons in the hippocampus are due to a dysfunction of GABAergic interneurons, and/or a decrease in their cholinergic control via nicotinic receptors (nAChRs). Electrophysiological recordings were obtained from pyramidal cells in the CA1 area of hippocampal slices from young (3-4 months old) and aged (25-30 months old) Sprague-Dawley rats. Synaptic GABA(A) receptor-mediated inhibitory postsynaptic currents and inhibitory postsynaptic potentials induced by stimulation of the stratum oriens were significantly smaller in aged rats. The frequency (but not amplitude) of spontaneous and miniature GABA inhibitory postsynaptic currents (IPSCs) was reduced in aged rats, suggesting a presynaptic alteration. Tetanic stimulation of cholinergic afferents to release endogenous acetylcholine, or an exogenous application of the nAChR agonist cytisine, increased the frequency of spontaneous IPSCs in young rats; however these effects were not evident in aged rats, indicating that the nicotinic control of GABA release is lowered during aging. None of these age-related alterations were reversed by a chronic treatment with donepezil, a cholinesterase inhibitor. Immunofluorescent labeling of GABA interneurons with somatostatin (SOM), parvalbumin (PV) or calbindin (CB), together with the vesicular acetylcholine transporter VAChT, revealed a selective loss of subpopulations of SOM and CB positive interneurons. This loss was associated with a general decrease in density of the cholinergic network in aged rats. Thus, the lower GABAergic inhibition observed in the aged rat hippocampus is due to a selective loss/dysfunction of subpopulations of GABAergic interneurons, associated with a widespread cholinergic deficit.

Age-related alterations in the properties of hippocampal pyramidal neurons among rat strains.

We compared age-related alterations in the electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons in three strains of rats (Sprague-Dawley, Fisher 344, and Wistar) at 3-4 and 25-32 months of age, using the in vitro slice preparation. The most consistent age-related alterations in the properties of rat hippocampal neurons were: a decrease in membrane excitability, a decrease in the amplitude and duration of inhibitory postsynaptic potentials and a decreased sensitivity to the effect of the cholinergic agonist carbachol. In contrast, no consistent alterations in calcium-dependent events were observed in these strains of rats. The age-related changes in the duration of the afterhyperpolarizations (AHPs) were different (and even opposite) depending on the strain studied. Our results show that age-related changes observed in a given strain are not necessarily present in all strains of the same species.

Loss of Calbindin-28K Immunoreactivity in Hippocampal Slices from Aged Rats: a Role for Calcium?

Calbindin-28K (CaBP) is a calcium-binding protein widely distributed in the brain. This protein appears to be involved in the sequestration and the translocation of intracellular free calcium. In this study, we have examined the distribution pattern of the structures immunoreactive for CaBP in the hippocampal formation from slices of young (4 months) and aged (24 - 27 months) rats previously submitted to electrophysiological measurements. We demonstrated a marked loss in the number of pyramidal cells immunoreactive for CaBP in aged rats as compared to young rats. A consistent decrease in the staining intensity was also revealed by optical density measurements. Some experiments have suggested that calcium homeostasis is modified in hippocampal neurons of aged rats. The loss of CaBP-like immunoreactivity (CaBP-LI) labelling could result from an increase in intracellular calcium concentrations. To support this hypothesis, we showed that in young rats (i) the CaBP-LI was enhanced in pyramidal neurons when the slice was preincubated in a calcium-free medium, and (ii) CaBP-LI was strongly decreased when the slice was preincubated in a high-calcium medium (5 mM) and when the entry of calcium into the cell was increased by a short application of an excitatory amino acid in the medium. Our results suggest that the loss of CaBP-LI in the hippocampus of aged rats could be due to an increase in intracellular calcium concentration. Preliminary observations of hippocampal slices at different times after induction of long-term potentiation (LTP) failed to show significant changes in CaBP immunoreactivity, suggesting that this calcium-binding protein is not directly involved in LTP processes.

Decrease in calbindin content significantly alters LTP but not NMDA receptor and calcium channel properties.

The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP) to the synaptic plasticity was investigated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-deficient mice. We showed that long-term potentiation (LTP) induced by tetanic stimulation in CaBP-deficient mice was impaired. The fundamental biophysical properties of NMDA receptors and their number were not modified in CaBP-deficient mice. We also demonstrated that the physiological properties of calcium channels were identical between genotypes. An insufficient Ca(2+) entry through NMDA receptors or calcium channels, or a decrease in NMDA receptor density are unlikely to explain this impairment of LTP. Interestingly, we showed that the loss of LTP was not prevented by glycine but was restored in the presence of a low concentration of the NMDA receptor antagonist D-APV (5 microM) and of the calcium chelator BAPTA-AM (5 microM). Moreover, we observed a loss of LTP in the wild-type mice when the postsynaptic tetanic-induced [Ca(2+)](i) rise is excessively increased. Conversely, a weaker tetanus stimulation allowed LTP induction and maintenance in CaBP-deficient mice. These results suggest that a higher cytosol [Ca(2+)](i), due to the decrease of CaBP expression may impair LTP induction and maintenance mechanisms without affecting the mechanisms of calcium entry. Thus, CaBP plays a critical role in long term synaptic plasticity by limiting the elevation of calcium rise in the cytosol to some appropriate spatio-temporal pattern.

Metabotropic glutamate receptors and calcium signalling in dendrites of hippocampal CA1 neurones.

We have combined patch-clamp recording with confocal microscopy to investigate how the synaptic activation of metabotropic glutamate receptors (mGluRs) may participate in the modulation of intracellular free calcium (Ca2+) in the dendrites of single CA1 pyramidal neurones, within hippocampal slices. Tetanic stimulation (100 Hz, 1 sec) of the Schaffer collateral-commissural pathway led to a transient rise in Ca2+ in the dendrites of neurones voltage- clamped at -35 mV, as determined using the fluorescent indicator fluo-3. The specific mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), applied at a concentration of 250 or 500 microM, reduced the size of the Ca2+ transient whilst either producing a small reduction or, more commonly, having no effect on the synaptic current evoked by the tetanus. These data suggest that the synaptic activation of mGluRs can contribute to Ca2+ signalling in hippocampal neurones.

Alterations in the properties of hippocampal pyramidal neurons in the aged rat.

The electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons were studied in slices from young (three to four months) and aged (25-32 months) Sprague-Dawley rats having previously performed two behavioral tasks. About 20% of the aged rats were impaired in either the spontaneous alternation task or the water maze task. Electrophysiological parameters were measured and compared in young and aged animals using intracellular recordings. No age-related differences were observed in membrane potential, input resistance, amplitude of action potentials or amplitude of calcium spikes. The amplitude and duration of individual afterhyperpolarizations following a single spike were unchanged. In contrast, the neuronal excitability was significantly decreased and the spike duration significantly enhanced in aged rats as compared to young rats. The comparison of afterhyperpolarizations (which follow a burst of spikes) between young and aged rats was more complex. An increase in the amplitude and duration of afterhyperpolarizations generally occurred in aged animals. However, this increase was not consistent among animals and was dependent on the holding potential of the neuron and on the number of action potentials used to trigger the afterhyperpolarization. The depolarizing effect of bath-applied carbachol, as well as the associated increase in membrane resistance were reduced in neurons from aged rats. In contrast, the effects of carbachol on the depression of synaptic events and the blockade of the afterhyperpolarizations were similar in young and aged animals. In addition, the amplitude of the slow cholinergic excitatory postsynaptic potential induced by stimulation of cholinergic afferents in the presence of physostigmine was also decreased in aged rats. Excitatory postsynaptic potentials and inhibitory postsynaptic potentials following electrical stimulation of stratum radiatum were compared. The amplitude and duration of excitatory postsynaptic potentials were increased in aged rats. The amplitude and duration of the fast inhibitory postsynaptic potential were not significantly affected in aged animals. In contrast, the duration of the slow inhibitory postsynaptic potential was decreased in aged rats. Since the mean baclofen-induced hyperpolarization was only slightly reduced in aged rats, the most likely explanation is a decrease in the release of GABA rather than an alteration in the postsynaptic response mediated by GABAB receptors. A statistically significant correlation was found between the degree of impairment in the spontaneous alternation task and the amplitude of the carbachol-induced depolarization.

Spatial learning and synaptic hippocampal plasticity in type 2 somatostatin receptor knock-out mice.

Somatostatin is implicated in a number of physiological functions in the CNS. These effects are elicited through the activation of at least five receptor subtypes. Among them, sst2 receptors appear the most widely expressed in the cortex and hippocampal region. However, the specific role of this somatostatin receptor subtype in these regions is largely undetermined. In this study, we investigated the role of the sst2 receptor in the hippocampus using mice invalidated for the sst2 gene (sst2 KO mice). Complementary experimental approaches were used. First, mice were tested in behavioral tests to explore the consequences of the gene deletion on learning and memory. Spatial discrimination learning in the radial maze was facilitated in sst2 KO mice, while operant learning of a bar-pressing task was slightly altered. Mice were then processed for electrophysiological study using the ex vivo hippocampal slice preparation. Extracellular recordings in the CA1 area showed an enhancement in glutamatergic (AMPA and NMDA) responses in sst2 KO mice which displayed an increase in the magnitude of the short-term potentiation and long-term depression. In contrast, long-term potentiation was not significantly altered. Taken together, these data demonstrate that somatostatin, acting via sst2 hippocampal receptors, may contribute to a global decrease in glutamate efficiency and consequently alter glutamate-dependent plasticity and spatial learning.

Effects of memantine and MK-801 on NMDA-induced currents in cultured neurones and on synaptic transmission and LTP in area CA1 of rat hippocampal slices.

The effects of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, memantine (1-amino-3,5-dimethyladamantane) and MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzocyclo-hepten-5,10-imin e maleate) were compared on synaptic transmission and long-term potentiation (LTP) in hippocampal slices and on NMDA-induced currents in cultured superior collicular neurones. 2. Memantine (10-100 microM) reversibly reduced, but did not abolish, NMDA receptor-mediated secondary population spikes recorded in area CA1 of hippocampal slices bathed in Mg(2+)-free artificial cerebrospinal fluid. 3. Memantine (100 microM) antagonized NMDA receptor-mediated excitatory postsynaptic currents recorded in area CA1 in a strongly voltage-dependent manner i.e. depressed to 11 +/- 4% of control at -35 mV and 95 +/- 5% of control at +40 mV (n = 9), with no apparent effect on response kinetics. 4. The effects of MK-801 and memantine on the induction of LTP were assessed after prolonged pre-incubations with these antagonists. When present for 6.6 +/- 0.4 h prior to tetanic stimulation, memantine blocked the induction of LTP with an IC50 of 11.6 +/- 0.53 microM. By comparison, similar long pre-incubations with MK-801 (6.4 +/- 0.4 h) blocked the induction of LTP with an IC50 of 0.13 +/- 0.02 microM. 5. Memantine and MK-801 reduced NMDA-induced currents in cultured superior colliculus neurones recorded at -70 mV with IC50s of 2.2 +/- 0.2 microM and 0.14 +/- 0.04 microM respectively. The effects of memantine were highly voltage-dependent and behaved as though the affinity decreased epsilon fold per 50 mV of depolarization (apparent delta = 0.71). In contrast, under the conditions used, MK-801 appeared to be much less voltage-dependent i.e. affinity decreased epsilon fold per 329 mV of depolarization (apparent delta = 0.15). 6. Depolarizing steps from -70 mV to +50 mV in the continuous presence of memantine (10 microM) caused a rapid relief of blockade of NMDA-induced currents from 83.7 +/- 1.9% to 21.8 +/- 1.8% (n = 5). This relief was best fitted by a double exponential function (17.2 +/- 11.7 and 698 +/- 204 ms), the faster component of which was most pronounced. 7. In conclusion, whereas MK-801 is equipotent in blocking NMDA-induced currents (at - 70 mV) and the induction of LTP, memantine is relatively less potent in blocking the induction of LTP. This is due to its rapid relief of blockade upon depolarization; a property which might explain its promising clinical profile in the treatment of chronic neurodegenerative diseases.

NMDA receptor activation in the aged rat hippocampus.

Age-related alterations of N-methyl-D-aspartate receptor (NMDAr) activation were investigated in the CA1 field of hippocampal slices from young (3-6 months old) and aged (25-33 months old) Sprague-Dawley rats by using ex vivo extracellular electrophysiological recording techniques. NMDAr-mediated field excitatory postsynaptic potentials (fEPSPs) were induced by electrical stimulation of glutamatergic fibers in a magnesium (Mg(2+))-free medium supplemented with the non-NMDAr antagonist CNQX. The fEPSPs were significantly smaller in aged rats, whereas the response of presynaptic afferent fibers remained unaffected. No significant age-related differences were found in the ability of Mg(2+) to depress the magnitude of NMDAr-mediated fEPSPs. The responsiveness of postsynaptic NMDAr to the agonist was assessed in both groups of animals. No age-related differences were recorded either in the depolarizing effect of bath-applied NMDA or in the magnitude of the depolarization after altering extracellular Mg(2+) concentration. Finally, short-term potentiation (STP) of excitatory transmission was studied in young and aged rats considering the pivotal role of NMDAr in synaptic plasticity. No age-related alterations of the magnitude and the time course of STP in response to 10 or 30Hz conditioning stimulation were found. Because of the decrease in the magnitude of NMDAr-mediated synaptic transmission in aged animals, the absence of obvious modifications of synaptic plasticity suggests the occurrence of compensatory mechanisms that are discussed.