Synaptic Plasticity 101: The Story of the AMPA Receptor for the Brain Stimulation Practitioner.

The fields of Neurobiology and Neuromodulation have never been closer. Consequently, the phrase "synaptic plasticity" has become very familiar to non-basic scientists, without actually being very familiar. We present the "Story of the AMPA receptor," an easy-to-understand "10,000 ft" narrative overview of synaptic plasticity, oriented toward the brain stimulation clinician or scientist without basic science training. Neuromodulation is unparalleled in its capacity to both modulate and probe plasticity, yet many are not comfortable with their grasp of the topic. Here, we describe the seminal discoveries that defined the canonical mechanisms of long-term potentiation (LTP), long-term depression (LTD), and homeostatic plasticity. We then provide a conceptual framework for how plasticity at the synapse is accomplished, describing the functional roles of N-methyl-d-aspartate (NMDA) receptors and calcium, their effect on calmodulin, phosphatases (ie, calcineurin), kinases (ie, calcium/calmodulin-dependent protein kinase [CaMKII]), and structural "scaffolding" proteins (ie, post-synaptic density protein [PSD-95]). Ultimately, we describe how these affect the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor. More specifically, AMPA receptor delivery to (LTP induction), removal from (LTD), or recycling within (LTP maintenance) the synapse is determined by the status of phosphorylation and protein binding at specific sites on the tails of AMPA receptor subunits: GluA1 and GluA2. Finally, we relate these to transcranial magnetic stimulation (TMS) treatment, highlighting evidences for LTP as the basis of high-frequency TMS therapy, and briefly touch on the role of plasticity for other brain stimulation modalities. In summary, we present Synaptic Plasticity 101 as a singular introductory reference for those less familiar with the mechanisms of synaptic plasticity.

Antibiotic prophylaxis for urinary tract infection after midurethral sling: a randomized controlled trial.

OBJECTIVE: Because of the reported high percentage of bladder infections after placement of a midurethral sling (8.9%-34%), this study was undertaken to determine if a 3-day postoperative course of a urinary antibiotic would significantly lower the incidence of urinary tract infection (UTI) among treated women. METHODS: Women who were planning outpatient vaginal surgery for stress incontinence were enrolled, after informed consent, and randomized to receive placebo or nitrofurantoin (100 mg 2 times a day) for 3 days after surgery. Research subjects and investigators were blinded to the randomization. Women were observed for signs and symptoms of UTI until 6 weeks after surgery. Sample size was calculated to have 80% power to detect a 15% difference in the primary outcome (α = 0.05). The primary outcome was analyzed using a χ analysis. RESULTS: Data were analyzed from 149 subjects (placebo, n = 75; drug, n = 74). Overall, 37 women (24.8%) were diagnosed with a UTI during the study period. The incidence of postoperative UTI was significantly lower in the treatment arm (17.6%) then in the placebo arm (32%; P = 0.04). CONCLUSIONS: A short (3-day) course of nitrofurantoin after outpatient sling surgery significantly reduces the incidence of postoperative bladder infection in the first 6 weeks after sling surgery.

A randomized comparison of bupivacaine versus saline during placement of tension-free vaginal tape.

OBJECTIVES: To compare postoperative urinary retention and pain control when bupivacaine versus saline for hydrodissection is used while placing tension-free vaginal tape midurethral slings. METHODS: A prospective, randomized, double-blind trial was performed after institutional review board approval. Sixty women were randomized to receive bupivacaine or saline for hydrodissection. Subjects and research team were blinded to subject assignments. Group characteristics were compared using the Student t test, the χ test, and the Mann-Whitney U test. Proportions of subjects with a successful postoperative voiding trial along with measurements of postoperative pain and analgesic use were compared using similar appropriate tests. The study was powered to detect differences in voiding trial success from an estimated 58% to greater than 90% with P < 0.05 and 0.8 power using 25 subjects per group. RESULTS: Thirty patients were allocated to each group. One subject in the saline-only group was excluded. Group characteristics were not different. After surgery, pain medication use (20/30 vs 25/29 for bupivacaine vs saline only; P = 0.08), pain scores (36 ± 22 vs 31 ± 24; P = 0.49), and successful voiding trials did not differ (14/30 vs 19/29; P = 0.14), whereas postvoid residuals did differ (225 ± 180 mL vs 140 ± 147 mL; P = 0.043). CONCLUSIONS: Bupivacaine was not seen to improve immediate postoperative pain after placement of a tension-free vaginal tape. It did not increase the risk of failing a postoperative voiding trial. Without an obvious benefit, the use of an additional medicine is not supported. We suggest saline alone be used for hydrodissection.

Effect of estrogen replacement on the histologic response to polypropylene mesh implanted in the rabbit vagina model.

OBJECTIVE: The aim of this study was to determine the effect of estrogen replacement after ovariectomy on the histologic response to polypropylene mesh implanted in rabbit vagina. STUDY DESIGN: Thirty rabbits were assigned to 5 groups: sham laparotomy, ovariectomy, ovariectomy-preoperative estrogen, ovariectomy-postoperative estrogen, or ovariectomy-preoperative and postoperative estrogen. Rabbits underwent sham surgery or ovariectomy and were infused with vehicle or 17beta-estradiol (200 microg/d) for 4 weeks ("preoperative" estrogen). Polypropylene mesh was implanted in the posterior vaginal wall, and rabbits were infused with vehicle or "postoperative" estrogen for an additional 8 weeks. Grafts were harvested and underwent histologic evaluation. RESULTS: Vaginal atrophy in ovariectomized rabbits was reversed by estrogen replacement. Scores for inflammation (P = .33) and neovascularization (P = .23) at the graft site were not different among estrogen replacement groups, but estrogen administration was associated with increased collagen deposition (P = .005). CONCLUSION: Estrogen replacement administered for 8 weeks postoperatively increases collagen deposition into polypropylene mesh.