Oxytocin increases inhibitory synaptic transmission and blocks development of long-term potentiation in the lateral amygdala.

Oxytocin (OT) is a neuroactive peptide that influences the processing of fearful stimuli in the amygdala. In the central nucleus of the amygdala, the activation of OT receptors alters neural activity and ultimately suppresses the behavioral response to a fear conditioned stimulus. Receptors for OT are also found in the lateral amygdala (LA), and infusion of OT into the basolateral amygdala complex affects the formation and consolidation of fear memories. Yet, how OT receptor activation alters neurons and neural networks in the LA is unknown. In this study we used whole cell electrophysiological recordings to determine how OT-receptor activation changes synaptic transmission and synaptic plasticity in the LA of Sprague-Dawley rats. Our results demonstrate that OT-receptor activation results in a 200% increase in spontaneous inhibitory transmission in the LA that leads to the activation of presynaptic GABAB receptors. The activation of these receptors inhibits excitatory transmission in the LA, blocking long-term potentiation of cortical inputs onto LA neurons. Hence, this study provides the first demonstration that OT influences synaptic transmission and plasticity in the LA, revealing a mechanism that could explain how OT regulates the formation and consolidation of conditioned fear memories in the amygdala.NEW & NOTEWORTHY This study investigates modulation of synaptic transmission by oxytocin (OT) in the lateral amygdala (LA). We demonstrate that OT induces transient increases in spontaneous GABAergic transmission by activating interneurons in the basolateral amygdala. The resultant increase in GABA release in the LA activates presynaptic GABAB receptors on both inhibitory and excitatory inputs onto LA neurons, reducing release probability at these synapses. We subsequently demonstrate that OT modulates synaptic plasticity at cortical inputs to the LA.

The effect of standard laboratory diets on estrogen signaling and spatial memory in male and female rats.

Phytoestrogens are plant-derived compounds that can modulate estrogen activity in the brain and periphery. Laboratory rodent diets are typically high in soy-based phytoestrogens and therefore may influence neurophysiological and behavioural measures that are sensitive to estrogen signaling. Here we assessed such measures in rats (males and females) fed Australian made diets that varied in their soy levels. We found that a low-soy diet promoted greater weight, and lower levels of plasma estradiol, particularly in male rats. It also produced sex-specific effects on estrogen receptor gene expression in the brain, increasing ESR2 expression in the hippocampus and prefrontal cortex in female rats, and decreasing dopamine D1 receptor gene expression in the striatum of both male and female rats. We also found a dietary effect on short-term place recognition memory, but this was independent of soy levels in the diet. These results demonstrate that the choice of rodent laboratory diet can influence physiology, neurobiology and behavior, particularly on measures related to estrogen signaling.

Baclofen acts in the central amygdala to reduce synaptic transmission and impair context fear conditioning.

The two main sub-divisions of the Central amygdala (CeA), the lateral-capsular (CeA-LC) and the medial (CeA-M), contain extensive networks of inhibitory interneurons. We have previously shown that activation of GABAB-receptors reduces excitatory transmission between axons of the pontine parabrachial nucleus and neurons of the CeA-LC by inhibiting glutamate release from presynaptic terminals13. Here we have characterised GABAB-receptor activation on other excitatory and inhibitory projections within the CeA. Using whole-cell, patch-clamp recordings, we found that the GABAB-receptor agonist baclofen significantly reduced excitatory and inhibitory transmission from all tested inputs into the CeA-LC and CeA-M. In all but one of the inputs, reductions in transmission were accompanied by an increase in paired pulse ratio, indicating that presynaptic GABAB-receptors acted to reduce the release probability of synaptic vesicles. To examine the impact of GABAB-receptors in the CeA on contextual fear-conditioning, we infused baclofen into the CeA immediately prior to training. Compared to vehicle-infused rats, baclofen-infused rats displayed significantly less freezing both during the final stages of the training period and at test 24 hours later. The results of this study demonstrate that, by suppressing excitatory and inhibitory transmission, activation of presynaptic GABAB-receptors in the CeA inhibits the development of context conditioned fear.

α2-adrenoceptor-mediated inhibition in the central amygdala blocks fear-conditioning.

The central amygdala is critical for the acquisition and expression of fear memories. This region receives a dense innervation from brainstem noradrenergic cell groups and has a high level of α2-adrenoceptor expression. Using whole-cell electrophysiological recordings from rat brain slices, we characterise the role of pre-synaptic α2-adrenoceptor in modulating discrete inhibitory and excitatory connections within both the lateral and medial division of the central amygdala. The selective α2-adrenoceptor agonist clonidine blocked the excitatory input from the pontine parabrachial neurons onto neurons of the lateral central amygdala. In addition, clonidine blocked inhibitory connections from the medial paracapsular intercalated cell mass onto both lateral and medial central amygdala neurons. To examine the behavioural consequence of α2-adrenoceptor-mediated inhibition of these inputs, we infused clonidine into the central amygdala prior to contextual fear-conditioning. In contrast to vehicle-infused rats, clonidine-infused animals displayed reduced levels of freezing 24 hours after training, despite showing no difference in freezing during the training session. These results reveal a role for α2-adrenoceptors within the central amygdala in the modulation of synaptic transmission and the formation of fear-memories. In addition, they provide further evidence for a role of the central amygdala in fear-memory formation.

Fetal intervention for myelomeningocele: effect on postnatal bladder function.

PURPOSE: Myelomeningocele is the most common congenital malformation of the central nervous system noted on prenatal ultrasound. Due to its significant postnatal sequelae, treatment in utero could potentially have a profound impact on the newborn. Others have reported fetal surgical techniques for in utero repair of myelomeningocele and its potential benefits on motor and neurological function. We report our urodynamic findings in the newborn after in utero repair of spina bifida in an effort to characterize postnatal bladder function. MATERIALS AND METHODS: A retrospective review of the fetal surgery database at University of California San Francisco was performed identifying patients with a diagnosis of myelomeningocele. Prenatal surgical repair of myelomeningocele was considered if a normal karyotype was present, no other significant congenital anomalies were evident and gestational age was less than 24 weeks. The spinal defects were in the lumbar or lumbosacral region. All surgery was performed before 24 weeks of gestations. RESULTS: Fetal surgery to correct myelomeningocele was performed in 6 patients. All patients were born premature at 32 weeks of gestation or less. Videourodynamics performed at age 1 month in 4 patients indicated decreased bladder capacity for weight, increased detrusor storage pressures and significant post-void residual. Hydronephrosis was demonstrated in 4 patients on renal/bladder ultrasound, and moderate vesicoureteral reflux was seen in 3. CONCLUSIONS: Patients with spinal bifida treated in utero appear to have the same changes in urodynamic parameters and anatomical abnormalities in the urinary tract as other children with spinal defects who have undergone standard postnatal care. In utero treatment of spinal bifida may expose the newborn to the effects of prematurity. The long-term effects on bladder function in the fetus after in utero repair of myelomeningocele remain unknown. A randomized controlled trial is necessary to evaluate long-term bladder function as well as other outcome variables in this experimental approach to patients with myelomeningocele.

Placement of artificial urinary sphincter in children and simultaneous gastrocystoplasty.

PURPOSE: Previous studies have described placement of an artificial urinary sphincter and simultaneous augmentation cystoplasty with a segment of bowel. Conclusions from these studies indicated that infection rates were higher and a staged approach should be undertaken. Others have suggested that concurrent urinary reconstruction with stomach and sphincter placement can be performed safely. Results comparing infection rates of simultaneous sphincter placement and gastrocystoplasty versus staged sphincter placement and augmentation cystoplasty using a segment of ileum or stomach versus sphincter placement alone in a pediatric population have not been previously described to our knowledge. We reviewed these various groups of patients to determine if the difference in infectious complications were clinically and statistically significant. MATERIALS AND METHODS: A retrospective review of medical records from 1986 to 1999 identified 28 pediatric patients (age 18 years or less) who had undergone placement of an AS800dagger artificial urinary sphincter. Data points were collected focusing on etiology of the neurogenic bladder, age at time of surgery, types of surgery performed, length of followup and complication rates. RESULTS: Complete data were available for 27 of the 28 patients. Neurogenic bladder was secondary to myelomeningocele in 25 cases, transverse myelitis in 1 and spinal cord injury in 2. Mean patient age at surgery was 12.7 years (range 6.1 to 18.2) and mean followup was 4.3 years (range 1 month to 13 years). Simultaneous gastrocystoplasty was performed in 7 cases (group 1), staged sphincter placement followed by augmentation cystoplasty with a segment of ileum or stomach was done in 8 (group 2) and 12 did not require bladder augmentation (group 3). Urethral device erosion requiring explantation was the most common complication, occurring in 3 patients in group 1 and 2 in group 3 (p = 0.101). Mean time to erosion was 22.1 months (range 2 to 46.4). Previous surgery (bladder neck or hernia repair) was a common factor in each group with complications. Urine cultures and culture of the explanted device were positive in 2 patients in group 1. CONCLUSIONS: Simultaneous placement of artificial urinary sphincter at the time of gastrocystoplasty can be performed in carefully selected patients, although those undergoing staged procedures did well without complications. Prior bladder neck surgery seems to be a significant risk for infection. A staged approach to lower urinary tract reconstruction would be more advantageous due to the absence of infection and erosion in those undergoing staged sphincter placement and augmentation cystoplasty.

Renal imaging with spiral CT scan: clinical applications.

Spiral computed tomography (CT) is an imaging modality that utilizes the rapid acquisition of cross-sectional data that can be reconstructed in a number of useful ways. We briefly describe the technology of spiral CT and recent advancements that have made spiral CT feasible. The advantages over conventional CT and angiography are reviewed. Urologic clinical applications are discussed including: detection of a crossing vessel prior to endopyelotomy for ureteropelvic junction (UPJ) obstruction, evaluating renal vascular anomalies preoperatively, and assistance in preoperative planning prior to partial nephrectomy in benign and malignant disease. Spiral CT has numerous advantages over conventional CT and angiography, and will likely have a notable role in future renal imaging.