Mechanisms and plasticity of chemogenically induced interneuronal suppression of principal cells.

How do firing patterns in a cortical circuit change when inhibitory neurons are excited? We virally expressed an excitatory designer receptor exclusively activated by a designer drug (Gq-DREADD) in all inhibitory interneuron types of the CA1 region of the hippocampus in the rat. While clozapine N-oxide (CNO) activation of interneurons suppressed firing of pyramidal cells, unexpectedly the majority of interneurons also decreased their activity. CNO-induced inhibition decreased over repeated sessions, which we attribute to long-term synaptic plasticity between interneurons and pyramidal cells. Individual interneurons did not display sustained firing but instead transiently enhanced their activity, interleaved with suppression of others. The power of the local fields in the theta band was unaffected, while power at higher frequencies was attenuated, likely reflecting reduced pyramidal neuron spiking. The incidence of sharp wave ripples decreased but the surviving ripples were associated with stronger population firing compared with the control condition. These findings demonstrate that DREADD activation of interneurons brings about both short-term and long-term circuit reorganization, which should be taken into account in the interpretation of chemogenic effects on behavior.

Venous Duplex Ultrasound Surveillance in the Neurosurgical Population: A Single-Center Quality Improvement Initiative.

BACKGROUND: Venous thromboembolism (VTE) represents a significant source of morbidity and mortality in the inpatient population and is considered a leading preventable cause of death among inpatients. Neurosurgical inpatients are of particular interest because of the greater rates of immobility, steroid use, and potential consequences of postoperative hemorrhage. A consensus protocol for VTE screening in this population has not yet been developed, and institutional protocols vary widely. METHODS: We performed a retrospective review of lower extremity venous duplex ultrasonography (VDUS) usage at our institution and applied this information to the development of a neurosurgery department protocol, with consideration of high-risk patient risk factors and indications for VDUS ordering. We then implemented this protocol, which consisted of preoperative screening of patients at high risk of VTE and limited postoperative surveillance, for a 6-month period and compared VDUS usage and VTE occurrence. RESULTS: Preoperative VDUS screening before nonemergent neurosurgical procedures in high-risk patients with active cancer, an inability to ambulate, or a history of deep vein thrombosis (DVT) identified proximal DVTs that were then treated. Postoperative routine surveillance VDUS scans only diagnosed incidental isolated calf DVT for which no clinically relevant sequelae occurred. Overall, postoperative surveillance VDUS usage decreased significantly (66.9% vs. 13.5%; P = 0.001). CONCLUSIONS: Our findings lend support to preoperative screening of high-risk patients and suggest that routine postoperative VDUS surveillance of asymptomatic patients is unnecessary.

Intraosseous Petrous Apex Schwannoma: Case Report and Review of Literature.

BACKGROUND: Intraosseous petrous apex schwannomas are an exceedingly rare entity; little is known about their epidemiology, natural history, and postoperative outcomes. CASE DESCRIPTION: Here, we present the fourth known case of a primary intraosseous schwannoma of the petrous apex: a 68-year-old woman presenting with diplopia, facial numbness, progressive intermittent vertigo, tinnitus, diminished hearing, and ataxia. She underwent a transtemporal approach for subtotal resection of the tumor with subsequent stereotactic radiosurgery. CONCLUSIONS: Our 2-year follow-up demonstrates slow growth and success of multimodal management in the treatment of these tumors. We review the 3 prior reports of petrous apex schwannomas and identify unifying radiographic and clinical characteristics to aid future diagnostic considerations of lesions of the petrous apex.

Vascularized Fibular Strut Autografts in Spinal Reconstruction after Resection of Vertebral Chordoma or Chondrosarcoma: A Retrospective Series.

BACKGROUND: Margin-free en bloc resection is the best medical practice for primary vertebral chordoma and chondrosarcoma. Spinal reconstruction following total spondylectomy requires reconstructive interbody graft (allograft, devascularized autograft, vascularized autograft, or cage constructs) and instrumentation. An important consideration when choosing grafts and instrumentation is the durability and the long-term success of the fusion without subsidence. OBJECTIVE: To evaluate the potential use of vascularized fibular autograft as a reconstructive strategy after en bloc resection. METHODS: We present a series of 16 patients who underwent spondylectomy for primary vertebral chordoma or chondrosarcoma with reconstruction using a vascularized fibular autograft and anterior/posterior instrumentation between January 2011 and April 2014. We report postoperative neurological outcome, 6-mo rates of fusion and graft subsidence, and other complications. RESULTS: Two patients passed away prior to 6-mo follow-up, and 1 patient was lost to follow-up. The mean follow-up time for the remaining 13 patients was 32 mo. Of these patients, 9 (69%) had evidence of fusion on the 6-mo follow-up computed tomography (CT) scan. Of the 4 patients who did not fuse, 2 had undergone surgery for new tumor diagnoses, 1 for hardware failure, and 1 for graft nonunion. Two patients (15%) had eventual graft subsidence along with hardware failure. CONCLUSIONS: Vascularized fibular strut grafts are a viable method for reconstruction following spondylectomy. We present the largest series of patients to date utilizing this technique. Further comparative studies examining vascularized grafts vs nonvascularized grafts or metallic cage constructs will be important in choosing the best reconstructive strategy.

Voltage-dependent intrinsic bursting in olfactory bulb Golgi cells.

In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods identified many other, nongranule cell types in the OB whose function remains mysterious. Within just the granule cell layer (GCL), Ramón y Cajal described multiple morphologically distinct subtypes of nongranule interneurons including large spiny Blanes cells which exhibit intrinsic persistent activity. Here, we define the intrinsic electrophysiology of a different nongranule interneuronal cell type in the GCL described by Ramón y Cajal, sparsely spiny Golgi cells in the rat OB. Golgi cells exhibit two distinct firing modes depending on the membrane potential: tonic firing and bursting. Golgi cells also generate rebound bursts following the offset of hyperpolarizing steps. We find that both low-threshold burst responses to depolarizing inputs and rebound bursts are blocked by nickel, an antagonist of T-type voltage-gated Ca2+ current. The state-dependent firing behavior we report in OB Golgi cells suggests that the function of these interneurons may dynamically shift from providing rhythmic potent inhibition of postsynaptic target neurons at sniffing frequencies to tonic, subtractive inhibition based on centrifugal modulatory input.