The development of effective pharmacotherapy for major depression is important because it is such... more The development of effective pharmacotherapy for major depression is important because it is such a widespread and debilitating mental disorder. Here, we have reviewed preclinical and clinical studies on tianeptine, an atypical antidepressant which ameliorates the adverse effects of stress on brain and memory. In animal studies, tianeptine has been shown to prevent stress-induced morphological sequelae in the hippocampus and amygdala, as well as to prevent stress from impairing synaptic plasticity in the prefrontal cortex and hippocampus. Tianeptine also has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory. We have further extended the findings on stress, memory and tianeptine here with two novel observations: 1) stress impairs spatial memory in adrenalectomized (ADX), thereby corticosterone-depleted, rats; and 2) the stress-induced impairment of memory in ADX rats is blocked by tianeptine. These findings are consistent with previous research which indicates that tianeptine produces anti-stress and memory-protective properties without altering the response of the hypothalamic-pituitary-adrenal axis to stress. We conclude with a discussion of findings which indicate that tianeptine accomplishes its anti-stress effects by normalizing stress-induced increases in glutamate in the hippocampus and amygdala. This finding is potentially relevant to recent research which indicates that abnormalities in glutamatergic neurotransmission are involved in the pathogenesis of depression. Ultimately, tianeptine’s prevention of depression-induced sequelae in the brain is likely to be a primary factor in its effectiveness as a pharmacological treatment for depression.
OBJECTIVE To review a series of children with anterior urethral valves and diverticula, to elucid... more OBJECTIVE To review a series of children with anterior urethral valves and diverticula, to elucidate the pathophysiology and optimal management of this entity. PATIENTS AND METHODS Nine cases (all boys; 1963 to 2003) were reviewed retrospectively. RESULTS Seven of nine boys had bulbar diverticula. Continuity between Cowper's duct and the diverticulum was noted endoscopically in two and confirmed radiographically in one. Initially, open surgery was curative but more recently endoscopic management has been the procedure of choice. CONCLUSION This series indicates that the distal lip of a ruptured syringocele may function as a flap-valve, leading to anterior urethral obstruction. Advances in imaging and endoscopic instruments have altered the mode of presentation and management of this entity. Editorial Comment: The authors present 9 cases of congenital anterior urethral valves identified during a 40-year period at a busy center. They document a close anatomical association between the anterior valve and Cowper's duct in 3 of 9 patients. This finding leads to speculation that a potential source of anterior urethral diverticulum is rupture of a Cowper's syringocele. The authors admit that it is difficult to tell whether a valve or diverticulum is the primary lesion in patients with anterior urethral valve. Because two thirds of the valves in this series were not associated with Cowper's duct, it may be that more than one etiology is responsible and more than one explanation is needed to explain the development of an anterior urethral valve. However, this article is important, since it shows that most of these cases can be managed endoscopically and that only those with a severe spongiosal defect require open reconstruction. Douglas A. Canning, M.D.
OBJECTIVE. Radionuclide voiding cystognaphy is generally advocated for the reevaluation of proved... more OBJECTIVE. Radionuclide voiding cystognaphy is generally advocated for the reevaluation of proved vesicouretenal reflux. The purpose of this study was to assess the efficacy of tailored low-dose fluoroscopic voiding cystourethrography for this purpose. SUBJECTS AND METHODS. Forty-five girls (2 years 9 months to 19 years 7 months old; mean, 7.4 years) who had proved neflux were examined with tailored low-dose voiding cystourethrography. The technique used a low-dose fluoroscopic system and KLEINMAN ET AL.
Vaccinations with amyloid-peptide (AB) can dramatically reduce amyloid deposition in a transgenic... more Vaccinations with amyloid-peptide (AB) can dramatically reduce amyloid deposition in a transgenic mouse model of Alzheimer's disease 1 . To determine if the vaccinations had deleterious or beneficial functional consequences, we tested eight months of A vaccination in a different ...
American Journal of Pharmacology and Toxicology, 2008
Over a century of behavioral research has shown that stress can exert both positive and negative ... more Over a century of behavioral research has shown that stress can exert both positive and negative effects on memory. We have explored the idea that the complex effects of stress on learning and memory can be characterized by hormetic-and non-hormetic dose-response functions, in which stress may either stimulate or impair brain memory mechanisms, depending, in part, on the timing and duration of the stress experience. Extensive work has shown that acute stress or corticosteroid administration has a biphasic effect specifically on hippocampus-dependent learning, memory and synaptic plasticity. We suggest that brief stress exerts a rapid enhancement of memory-related functions of the hippocampus, produced by the amygdala-induced activation of hippocampal synaptic plasticity in conjunction with excitatory effects of neuromodulators, including glucocorticoids, norepinephrine, corticotropin-releasing hormone, acetylcholine and dopamine. We propose that the rapid stress-induced activation of the amygdala-hippocampus brain memory system results in a linear (non-hormetic) dose-response relation between emotional strength and memory formation. In response to more prolonged stress, a delayed inhibition of hippocampal function develops, which can be attributed to compensatory cellular responses which protect hippocampal neurons from excitotoxicity. The inhibition of hippocampal functioning in response to prolonged stress is potentially relevant to the well-described curvilinear (hormetic) dose-response relationship between arousal and memory. In summary, our emphasis on the temporal features of stress-brain interactions addresses how stress can activate, as well as impair, hippocampal functioning to produce differently shaped (nonhormetic/hormetic) stress-memory dose response functions.
We review our surgical experience with the management of retrovesical cystic anomalies using robo... more We review our surgical experience with the management of retrovesical cystic anomalies using robot-assisted laparoscopic techniques. Materials and Methods: We retrospectively reviewed the presentation, diagnosis and treatment of 6 patients 28 months to 22 years old with retrovesical cystic anomalies who underwent robot-assisted laparoscopic excision at our hospital between January 2006 and November 2010. Results: Presenting signs and symptoms included urinary retention, lower urinary tract symptoms, abdominal pain and repeated epididymitis. Associated anomalies consisted of hypospadias, vesicoureteral reflux, renal agenesis, 5alphareductase deficiency, premature adrenarche and cryptorchidism. Cystic anomalies ranged from 3 to 6 cm long. The final diagnoses were prostatic utricular cyst, müllerian duct cyst and seminal vesicle cyst. Ectopic insertion of vas into the cyst was found in 4 cases, requiring ligation of the affected vas in 3. Mean Ϯ SD operative time including cystoscopy was 198 Ϯ 23.8 minutes, and estimated blood loss ranged from 5 to 10 ml. Mean Ϯ SD hospital stay was 1.33 Ϯ 0.52 days. All patients had resumed their regular activities within 2 weeks postoperatively. De novo contralateral epididymitis developed 2 months postoperatively in 1 patient. Otherwise, there was no recurrence of cystic mass or presenting signs or symptoms during followup of 3 to 56 months. Conclusions: In the management of retrovesical cystic anomalies robot-assisted laparoscopic excision affords a natural extension of conventional laparoscopy with the additional advantages of 3-dimensional vision and ease of instrument control.
Shockwave lithotripsy (SWL) is being used increasingly as a therapeutic modality for childhood ur... more Shockwave lithotripsy (SWL) is being used increasingly as a therapeutic modality for childhood urolithiasis. We reported our experience and results of SWL in the pediatric population. The 59 renal units (RU) of 54 patients were retrospectively reviewed. The mean patient age was 10+/-3.5 years. All patients were treated with the Lithostar lithotripter in outpatient settings. Those with positive culture results were treated under appropriate antibiotic coverage. Seven patients were treated under general anesthesia and the rest under sedoanalgesia. Shielding of the lung fields or gonads was not used. For the upper pole stones, protection of the lungs was accomplished by elevating the upper half of the body with supportive pillows, thus moving the kidney away from the lung fields. Six RUs were catheterized via double-pigtail ureteral catheters or by percutaneous nephrostomy tube prior to treatment. The average stone load was 1.8+/-2.5 cm2. Patients were treated with an average of 2.5 sessions. A total of 1000 to 2500 shockwaves were delivered between 14.5 and 17.8 kV. Routine spasmolytic treatment was not initiated. The stone-free rate was 64%, and clinically insignificant residual fragments (CIRF) were present in 29% of RUs; thus, the success rate was 93%. Fever that necessitated hospitalization occurred in one patient. No other complications were seen except skin bruising and early hematuria. Shockwave lithotripsy is a safe and effective treatment modality for childhood stones of appropriate size and radiologic characteristics.
This study provides a comprehensive behavioral characterization during aging of transgenic mice b... more This study provides a comprehensive behavioral characterization during aging of transgenic mice bearing both presenilin-1 (PS1) and amyloid precursor protein (APP) mutations. Doubly transgenic mice and non-transgenic controls were evaluated at ages wherein 670,671 b-amyloid (Ab) neuropathology in APP1PS1 mice is low (5-7 months) or very extensive (15-17 months). Progressive cognitive impairment was observed in transgenic mice for both water maze acquisition and radial arm water maze working memory. However, transgenicity did not affect Y-maze alternations, circular platform performance, standard water maze retention, or visible platform recognition at either age, nor did transgenicity affect anxiety levels in elevated plus-maze testing. In sensorimotor tasks, transgenic mice showed a progressive increase in open field activity, a progressive impairment in string agility, and an early-onset impairment in balance beam. None of these sensorimotor changes appeared to be contributory to any cognitive impairments observed, however. Non-transgenic mice showed no progressive behavioral change in any measure evaluated. Given the age-related cognitive impairments presently observed in APP1PS1 transgenic mice and their progressive Ab deposition / neuroinflammation, Ab neuropathology could be involved in these progressive cognitive impairments. As such, the APP1PS1 transgenic mouse offers unique opportunities to develop therapeutics to treat or prevent Alzheimer's Disease through modulation of Ab deposition / neuroinflammation.
The medial temporal lobe, including the entorhinal cortex, the amygdala and the hippocampus, has ... more The medial temporal lobe, including the entorhinal cortex, the amygdala and the hippocampus, has an important role in learning and memory, and its circuits exhibit synaptic plasticity (long-term potentiation [LTP]). The entorhinal cortex is positioned to exert a potent influence on the amygdala and the hippocampus given its extensive monosynaptic projections to both areas. We therefore studied the effects of activation of the entorhinal cortex with simultaneous recording of LTP in the hippocampus and amygdala in the anesthetized rat. Burst stimulation of the lateral entorhinal cortex induced LTP simultaneously in the basal amygdaloid nucleus and in the dentate gyrus. However, the mechanisms involved in the induction of LTP in the two areas differed. The Nmethyl-D-aspartate receptor antagonist 3-[(؎)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid delivered 1 h before LTP induction (10 mg/kg, i.p.), blocked LTP in the dentate gyrus but not in the amygdala. In addition we found that the basal amygdala as well as the dentate gyrus sustained latephase LTP (10 h) which may participate in memory encoding and/or modulation processes. Overall, the results suggest a coordinating role for the entorhinal cortex by simultaneously modulating activity and plasticity in these structures, albeit through different mechanisms. Interactive encoding of this sort is believed to endow memories with a different, more integrative, quality than when either pathway is activated alone.
Stress impairs hippocampal long-term potentiation (LTP), a model of synaptic plasticity that is a... more Stress impairs hippocampal long-term potentiation (LTP), a model of synaptic plasticity that is assumed to underlie memory formation. In the amygdala, little is known about the effects of stress on LTP, or about its longevity. Here we assessed the ability of entorhinal cortex (EC) stimulation to induce LTP simultaneously in the basal amygdaloid nucleus (B) and in the dentate gyrus (DG) of freely behaving Wistar rats. We also tested whether LTP persists over days. Once established, we investigated the effects of acute vs. repeated inescapable stressful experiences on LTP in both structures. Results show that B, like DG, sustained LTP for 7 days. Furthermore, a single exposure to moderate stress facilitated LTP in B but did not affect DG LTP. Stress re-exposure inhibited LTP in DG but only long-lasting LTP (>3 days) in B. Behaviourally, animals exhibited a higher immobility when re-exposed to the stressor than with a single/first exposure. These data support a role for B in memory storage. Furthermore, they support a differential involvement of the amygdala and hippocampus in memory formation and storage depending on the emotional characteristics of the experience.
Adult male rats were fed a low or high fat diet and given psychosocial stress (crowded and unstab... more Adult male rats were fed a low or high fat diet and given psychosocial stress (crowded and unstable housing with daily predator exposure) for 3 weeks. Neither stress nor high fat diet, alone, produced dendritic atrophy; only the group given the combination of stress and high fat diet ...
The responses of single neurons in the primary and secondary auditory cortex of cat were recorded... more The responses of single neurons in the primary and secondary auditory cortex of cat were recorded during the presentation of sequences consisting of five tones of different frequencies. Discharges to tones within these sequences usually (84%) exhibited a dependence on the 'direction' ...
Classical conditioning produces frequency-specific plasticity of receptive fields (RFs) of single... more Classical conditioning produces frequency-specific plasticity of receptive fields (RFs) of single neurons in cat auditory cortex (Diamond & Weinberger, 1986). In this article we show that although plasticity may be observed during both training trials and determination of RFs, it is ...
Stress-the International Journal on The Biology of Stress, 2010
The persistent intrusion of remote traumatic memories in people with post-traumatic stress disord... more The persistent intrusion of remote traumatic memories in people with post-traumatic stress disorder (PTSD) may contribute to the impairment of their ongoing hippocampal and prefrontal cortical functioning. In the current work, we have developed a rodent analogue of the intrusive memory phenomenon. We studied the influence of the activation of a remote traumatic memory in rats on their ability to retrieve a newly formed hippocampus-dependent memory. Adult male Sprague-Dawley rats were given inhibitory avoidance (IA) training, and then 24 h or 1, 6 or 12 months later, the same rats were trained to learn, and then remember across a 30-min delay period, the location of a hidden escape platform in the radial-arm water maze (RAWM). When IA-trained rats spent the 30-min delay period in the IA apparatus, they exhibited intact remote (1-year old) memory of the shock experience. More importantly, activation of the rats' memory of the shock experience profoundly impaired their ability to retrieve the newly formed spatial memory of the hidden platform location in the RAWM. Our finding that reactivation of a remote emotional memory exerted an intrusive effect on new spatial memory processing in rats provides a novel approach toward understanding how intrusive memories of traumatic experiences interfere with ongoing cognitive processing in people with PTSD.
ObjectiveTo determine the frequency of concordance of testicular anatomical location between both... more ObjectiveTo determine the frequency of concordance of testicular anatomical location between both undescended testes based on surgical findings.
The development of effective pharmacotherapy for major depression is important because it is such... more The development of effective pharmacotherapy for major depression is important because it is such a widespread and debilitating mental disorder. Here, we have reviewed preclinical and clinical studies on tianeptine, an atypical antidepressant which ameliorates the adverse effects of stress on brain and memory. In animal studies, tianeptine has been shown to prevent stress-induced morphological sequelae in the hippocampus and amygdala, as well as to prevent stress from impairing synaptic plasticity in the prefrontal cortex and hippocampus. Tianeptine also has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory. We have further extended the findings on stress, memory and tianeptine here with two novel observations: 1) stress impairs spatial memory in adrenalectomized (ADX), thereby corticosterone-depleted, rats; and 2) the stress-induced impairment of memory in ADX rats is blocked by tianeptine. These findings are consistent with previous research which indicates that tianeptine produces anti-stress and memory-protective properties without altering the response of the hypothalamic-pituitary-adrenal axis to stress. We conclude with a discussion of findings which indicate that tianeptine accomplishes its anti-stress effects by normalizing stress-induced increases in glutamate in the hippocampus and amygdala. This finding is potentially relevant to recent research which indicates that abnormalities in glutamatergic neurotransmission are involved in the pathogenesis of depression. Ultimately, tianeptine’s prevention of depression-induced sequelae in the brain is likely to be a primary factor in its effectiveness as a pharmacological treatment for depression.
OBJECTIVE To review a series of children with anterior urethral valves and diverticula, to elucid... more OBJECTIVE To review a series of children with anterior urethral valves and diverticula, to elucidate the pathophysiology and optimal management of this entity. PATIENTS AND METHODS Nine cases (all boys; 1963 to 2003) were reviewed retrospectively. RESULTS Seven of nine boys had bulbar diverticula. Continuity between Cowper's duct and the diverticulum was noted endoscopically in two and confirmed radiographically in one. Initially, open surgery was curative but more recently endoscopic management has been the procedure of choice. CONCLUSION This series indicates that the distal lip of a ruptured syringocele may function as a flap-valve, leading to anterior urethral obstruction. Advances in imaging and endoscopic instruments have altered the mode of presentation and management of this entity. Editorial Comment: The authors present 9 cases of congenital anterior urethral valves identified during a 40-year period at a busy center. They document a close anatomical association between the anterior valve and Cowper's duct in 3 of 9 patients. This finding leads to speculation that a potential source of anterior urethral diverticulum is rupture of a Cowper's syringocele. The authors admit that it is difficult to tell whether a valve or diverticulum is the primary lesion in patients with anterior urethral valve. Because two thirds of the valves in this series were not associated with Cowper's duct, it may be that more than one etiology is responsible and more than one explanation is needed to explain the development of an anterior urethral valve. However, this article is important, since it shows that most of these cases can be managed endoscopically and that only those with a severe spongiosal defect require open reconstruction. Douglas A. Canning, M.D.
OBJECTIVE. Radionuclide voiding cystognaphy is generally advocated for the reevaluation of proved... more OBJECTIVE. Radionuclide voiding cystognaphy is generally advocated for the reevaluation of proved vesicouretenal reflux. The purpose of this study was to assess the efficacy of tailored low-dose fluoroscopic voiding cystourethrography for this purpose. SUBJECTS AND METHODS. Forty-five girls (2 years 9 months to 19 years 7 months old; mean, 7.4 years) who had proved neflux were examined with tailored low-dose voiding cystourethrography. The technique used a low-dose fluoroscopic system and KLEINMAN ET AL.
Vaccinations with amyloid-peptide (AB) can dramatically reduce amyloid deposition in a transgenic... more Vaccinations with amyloid-peptide (AB) can dramatically reduce amyloid deposition in a transgenic mouse model of Alzheimer's disease 1 . To determine if the vaccinations had deleterious or beneficial functional consequences, we tested eight months of A vaccination in a different ...
American Journal of Pharmacology and Toxicology, 2008
Over a century of behavioral research has shown that stress can exert both positive and negative ... more Over a century of behavioral research has shown that stress can exert both positive and negative effects on memory. We have explored the idea that the complex effects of stress on learning and memory can be characterized by hormetic-and non-hormetic dose-response functions, in which stress may either stimulate or impair brain memory mechanisms, depending, in part, on the timing and duration of the stress experience. Extensive work has shown that acute stress or corticosteroid administration has a biphasic effect specifically on hippocampus-dependent learning, memory and synaptic plasticity. We suggest that brief stress exerts a rapid enhancement of memory-related functions of the hippocampus, produced by the amygdala-induced activation of hippocampal synaptic plasticity in conjunction with excitatory effects of neuromodulators, including glucocorticoids, norepinephrine, corticotropin-releasing hormone, acetylcholine and dopamine. We propose that the rapid stress-induced activation of the amygdala-hippocampus brain memory system results in a linear (non-hormetic) dose-response relation between emotional strength and memory formation. In response to more prolonged stress, a delayed inhibition of hippocampal function develops, which can be attributed to compensatory cellular responses which protect hippocampal neurons from excitotoxicity. The inhibition of hippocampal functioning in response to prolonged stress is potentially relevant to the well-described curvilinear (hormetic) dose-response relationship between arousal and memory. In summary, our emphasis on the temporal features of stress-brain interactions addresses how stress can activate, as well as impair, hippocampal functioning to produce differently shaped (nonhormetic/hormetic) stress-memory dose response functions.
We review our surgical experience with the management of retrovesical cystic anomalies using robo... more We review our surgical experience with the management of retrovesical cystic anomalies using robot-assisted laparoscopic techniques. Materials and Methods: We retrospectively reviewed the presentation, diagnosis and treatment of 6 patients 28 months to 22 years old with retrovesical cystic anomalies who underwent robot-assisted laparoscopic excision at our hospital between January 2006 and November 2010. Results: Presenting signs and symptoms included urinary retention, lower urinary tract symptoms, abdominal pain and repeated epididymitis. Associated anomalies consisted of hypospadias, vesicoureteral reflux, renal agenesis, 5alphareductase deficiency, premature adrenarche and cryptorchidism. Cystic anomalies ranged from 3 to 6 cm long. The final diagnoses were prostatic utricular cyst, müllerian duct cyst and seminal vesicle cyst. Ectopic insertion of vas into the cyst was found in 4 cases, requiring ligation of the affected vas in 3. Mean Ϯ SD operative time including cystoscopy was 198 Ϯ 23.8 minutes, and estimated blood loss ranged from 5 to 10 ml. Mean Ϯ SD hospital stay was 1.33 Ϯ 0.52 days. All patients had resumed their regular activities within 2 weeks postoperatively. De novo contralateral epididymitis developed 2 months postoperatively in 1 patient. Otherwise, there was no recurrence of cystic mass or presenting signs or symptoms during followup of 3 to 56 months. Conclusions: In the management of retrovesical cystic anomalies robot-assisted laparoscopic excision affords a natural extension of conventional laparoscopy with the additional advantages of 3-dimensional vision and ease of instrument control.
Shockwave lithotripsy (SWL) is being used increasingly as a therapeutic modality for childhood ur... more Shockwave lithotripsy (SWL) is being used increasingly as a therapeutic modality for childhood urolithiasis. We reported our experience and results of SWL in the pediatric population. The 59 renal units (RU) of 54 patients were retrospectively reviewed. The mean patient age was 10+/-3.5 years. All patients were treated with the Lithostar lithotripter in outpatient settings. Those with positive culture results were treated under appropriate antibiotic coverage. Seven patients were treated under general anesthesia and the rest under sedoanalgesia. Shielding of the lung fields or gonads was not used. For the upper pole stones, protection of the lungs was accomplished by elevating the upper half of the body with supportive pillows, thus moving the kidney away from the lung fields. Six RUs were catheterized via double-pigtail ureteral catheters or by percutaneous nephrostomy tube prior to treatment. The average stone load was 1.8+/-2.5 cm2. Patients were treated with an average of 2.5 sessions. A total of 1000 to 2500 shockwaves were delivered between 14.5 and 17.8 kV. Routine spasmolytic treatment was not initiated. The stone-free rate was 64%, and clinically insignificant residual fragments (CIRF) were present in 29% of RUs; thus, the success rate was 93%. Fever that necessitated hospitalization occurred in one patient. No other complications were seen except skin bruising and early hematuria. Shockwave lithotripsy is a safe and effective treatment modality for childhood stones of appropriate size and radiologic characteristics.
This study provides a comprehensive behavioral characterization during aging of transgenic mice b... more This study provides a comprehensive behavioral characterization during aging of transgenic mice bearing both presenilin-1 (PS1) and amyloid precursor protein (APP) mutations. Doubly transgenic mice and non-transgenic controls were evaluated at ages wherein 670,671 b-amyloid (Ab) neuropathology in APP1PS1 mice is low (5-7 months) or very extensive (15-17 months). Progressive cognitive impairment was observed in transgenic mice for both water maze acquisition and radial arm water maze working memory. However, transgenicity did not affect Y-maze alternations, circular platform performance, standard water maze retention, or visible platform recognition at either age, nor did transgenicity affect anxiety levels in elevated plus-maze testing. In sensorimotor tasks, transgenic mice showed a progressive increase in open field activity, a progressive impairment in string agility, and an early-onset impairment in balance beam. None of these sensorimotor changes appeared to be contributory to any cognitive impairments observed, however. Non-transgenic mice showed no progressive behavioral change in any measure evaluated. Given the age-related cognitive impairments presently observed in APP1PS1 transgenic mice and their progressive Ab deposition / neuroinflammation, Ab neuropathology could be involved in these progressive cognitive impairments. As such, the APP1PS1 transgenic mouse offers unique opportunities to develop therapeutics to treat or prevent Alzheimer's Disease through modulation of Ab deposition / neuroinflammation.
The medial temporal lobe, including the entorhinal cortex, the amygdala and the hippocampus, has ... more The medial temporal lobe, including the entorhinal cortex, the amygdala and the hippocampus, has an important role in learning and memory, and its circuits exhibit synaptic plasticity (long-term potentiation [LTP]). The entorhinal cortex is positioned to exert a potent influence on the amygdala and the hippocampus given its extensive monosynaptic projections to both areas. We therefore studied the effects of activation of the entorhinal cortex with simultaneous recording of LTP in the hippocampus and amygdala in the anesthetized rat. Burst stimulation of the lateral entorhinal cortex induced LTP simultaneously in the basal amygdaloid nucleus and in the dentate gyrus. However, the mechanisms involved in the induction of LTP in the two areas differed. The Nmethyl-D-aspartate receptor antagonist 3-[(؎)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid delivered 1 h before LTP induction (10 mg/kg, i.p.), blocked LTP in the dentate gyrus but not in the amygdala. In addition we found that the basal amygdala as well as the dentate gyrus sustained latephase LTP (10 h) which may participate in memory encoding and/or modulation processes. Overall, the results suggest a coordinating role for the entorhinal cortex by simultaneously modulating activity and plasticity in these structures, albeit through different mechanisms. Interactive encoding of this sort is believed to endow memories with a different, more integrative, quality than when either pathway is activated alone.
Stress impairs hippocampal long-term potentiation (LTP), a model of synaptic plasticity that is a... more Stress impairs hippocampal long-term potentiation (LTP), a model of synaptic plasticity that is assumed to underlie memory formation. In the amygdala, little is known about the effects of stress on LTP, or about its longevity. Here we assessed the ability of entorhinal cortex (EC) stimulation to induce LTP simultaneously in the basal amygdaloid nucleus (B) and in the dentate gyrus (DG) of freely behaving Wistar rats. We also tested whether LTP persists over days. Once established, we investigated the effects of acute vs. repeated inescapable stressful experiences on LTP in both structures. Results show that B, like DG, sustained LTP for 7 days. Furthermore, a single exposure to moderate stress facilitated LTP in B but did not affect DG LTP. Stress re-exposure inhibited LTP in DG but only long-lasting LTP (>3 days) in B. Behaviourally, animals exhibited a higher immobility when re-exposed to the stressor than with a single/first exposure. These data support a role for B in memory storage. Furthermore, they support a differential involvement of the amygdala and hippocampus in memory formation and storage depending on the emotional characteristics of the experience.
Adult male rats were fed a low or high fat diet and given psychosocial stress (crowded and unstab... more Adult male rats were fed a low or high fat diet and given psychosocial stress (crowded and unstable housing with daily predator exposure) for 3 weeks. Neither stress nor high fat diet, alone, produced dendritic atrophy; only the group given the combination of stress and high fat diet ...
The responses of single neurons in the primary and secondary auditory cortex of cat were recorded... more The responses of single neurons in the primary and secondary auditory cortex of cat were recorded during the presentation of sequences consisting of five tones of different frequencies. Discharges to tones within these sequences usually (84%) exhibited a dependence on the 'direction' ...
Classical conditioning produces frequency-specific plasticity of receptive fields (RFs) of single... more Classical conditioning produces frequency-specific plasticity of receptive fields (RFs) of single neurons in cat auditory cortex (Diamond & Weinberger, 1986). In this article we show that although plasticity may be observed during both training trials and determination of RFs, it is ...
Stress-the International Journal on The Biology of Stress, 2010
The persistent intrusion of remote traumatic memories in people with post-traumatic stress disord... more The persistent intrusion of remote traumatic memories in people with post-traumatic stress disorder (PTSD) may contribute to the impairment of their ongoing hippocampal and prefrontal cortical functioning. In the current work, we have developed a rodent analogue of the intrusive memory phenomenon. We studied the influence of the activation of a remote traumatic memory in rats on their ability to retrieve a newly formed hippocampus-dependent memory. Adult male Sprague-Dawley rats were given inhibitory avoidance (IA) training, and then 24 h or 1, 6 or 12 months later, the same rats were trained to learn, and then remember across a 30-min delay period, the location of a hidden escape platform in the radial-arm water maze (RAWM). When IA-trained rats spent the 30-min delay period in the IA apparatus, they exhibited intact remote (1-year old) memory of the shock experience. More importantly, activation of the rats' memory of the shock experience profoundly impaired their ability to retrieve the newly formed spatial memory of the hidden platform location in the RAWM. Our finding that reactivation of a remote emotional memory exerted an intrusive effect on new spatial memory processing in rats provides a novel approach toward understanding how intrusive memories of traumatic experiences interfere with ongoing cognitive processing in people with PTSD.
ObjectiveTo determine the frequency of concordance of testicular anatomical location between both... more ObjectiveTo determine the frequency of concordance of testicular anatomical location between both undescended testes based on surgical findings.
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Papers by DAVID DIAMOND