Emerging Activity Patterns and Synaptogenesis in Dissociated Hippocampal Cultures.

Cultures of dissociated hippocampal neurons display a stereotypical development of network activity patterns within the first three weeks of maturation. During this process, network connections develop and the associated spiking patterns range from increasing levels of activity in the first two weeks to regular bursting activity in the third week of maturation. Characterization of network structure is important to examine the mechanisms underlying the emergent functional organization of neural circuits. To accomplish this, confocal microscopy techniques have been used and several automated synapse quantification algorithms based on (co)localization of synaptic structures have been proposed recently. However, these approaches suffer from the arbitrary nature of intensity thresholding and the lack of correction for random-chance colocalization. To address this problem, we developed and validated an automated synapse quantification algorithm that requires minimal operator intervention. Next, we applied our approach to quantify excitatory and inhibitory synaptogenesis using confocal images of dissociated hippocampal neuronal cultures captured at 5, 8, 14 and 20 days in vitro, the time period associated with the development of distinct neuronal activity patterns. As expected, we found that synaptic density increased with maturation, coinciding with increasing spiking activity in the network. Interestingly, the third week of the maturation exhibited a reduction in excitatory synaptic density suggestive of synaptic pruning that coincided with the emergence of regular bursting activity in the network.

Solitary Infiltrating Meningioma of the Trochlear Nerve: Case Report.

We report the case of a solitary meningioma infiltrating the trochlear nerve, the first in a patient without a neurocutaneous disorder or cavernous sinus involvement. The patient presented with diplopia was found to have a focal enhancing mass encompassing the trochlear nerve. Following surgical resection, pathological examination showed meningioma infiltrating the nerve itself, demonstrated on the included pathology images. A review of the literature and discussion of meningiomas infiltrating cranial nerves are included.

Myelopathy after cervical disc arthroplasty due to progression of spondylosis at the index level: case report.

Cervical disc arthroplasty (CDA) has emerged as a popular alternative to anterior cervical discectomy and fusion (ACDF) for the surgical treatment of cervical degenerative disc disease. CDA has been well studied, with efficacy reported to be equivalent to or better than that seen with ACDF, and it is associated with a consistently low incidence of adverse events. The development or progression of myelopathy after CDA is a particularly rare occurrence. In this report, the authors describe the first known case of recurrence of myelopathy at the index level of surgery after CDA implantation due the continuation of the spondylitic process after placement of the artificial disc.

Supraorbital Keyhole Craniotomy for Basilar Artery Aneurysms: Accounting for the "Cliff" Effect.

BACKGROUND: Treatment of basilar artery aneurysms is challenging. While endovascular techniques have dominated, there still remain circumstances where open surgical clipping is required or preferred. Minimally invasive "keyhole" approaches are being used more frequently to provide the durability of surgical clipping with a lower morbidity profile; however, careful patient selection is required. The supraorbital "keyhole" approach has been described for the treatment of basilar artery aneurysms, but careful assessment of the basilar exposure is necessary to ensure proper visualization of the aneurysm and ability to obtain proximal vascular control. Various methods of estimating the basilar artery exposure in this approach have been described, including the anterior skull base line and the posterior clinoid line, but both are unreliable and inaccurate. OBJECTIVE: To propose a new method, the orbital roof-dorsum line, to simply and accurately predict the basilar artery exposure. METHODS: CT angiograms for 20 consecutive unique patients were analyzed to obtain the anterior skull base line, posterior clinoid line, and the orbital roof-dorsum line. CT angiograms were then loaded onto a Stealth neuronavigation system (Medtronic, Minneapolis, Minnesota) to obtain "true" visualization lengths. A case illustration is presented. RESULTS: Pairwise comparison tests demonstrated that both the anterior skull base and the posterior clinoid estimation lines differed significantly from the "true" value ( P < .0001). Our orbital roof-dorsum estimation provided results that accurately predicted the "true" value ( P = .71). CONCLUSION: The orbital roof-dorsum line provides a simple and reliable method of estimating basilar artery exposure and should be used whenever considering patients for surgical clipping by this approach.

Radiographic Assessment of the presigmoid retrolabyrinthine approach.

BACKGROUND: Lesions of the petroclival fissure are difficult to access surgically. Both retrosigmoid and presigmoid retrolabyrinthine approaches have been described to successfully treat these complex tumors. The retrosigmoid approach offers quick and familiar access, whereas the presigmoid retrolabyrinthine approach reduces the operative distance and the need for cerebellar retraction. The presigmoid retrolabyrinthine approach, however, is constrained by anatomical limits that can be subject to patient variation. We sought to characterize the surgically relevant variation to guide preoperative assessment. METHODS: One hundred and seventy-seven high-resolution computed tomography scans of the head (without preexisting pathology) were reviewed. Three hundred and fifty-four temporal bone scans were analyzed for level of aeration, size of Trautmann's triangle dura, and petrous slope. Petrous slope is the angle between the anterior sigmoid sinus and the petroclival fissure at the level of the internal acoustic canal. RESULTS: Trautmann's triangle area had a mean of 185.15 mm2 (range 71.4-426.7 mm2). Petrous slope had a mean value of 149° (range 106-178°). Increasing aeration was found to be correlated with decreasing petrous slope and decreasing Trautmann's triangle area. CONCLUSION: The presigmoid retrolabyrinthine approach is uniquely confined. Variations in temporal bone anatomy can have dramatic impacts on the operative time, risk profile, and final exposure. Preoperative assessment is critical in guiding the surgeon on the appropriateness of approach. Preoperative measurement of Trautmann's triangle, petrous slope, and aeration can help to reduce surgical morbidity.

Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents.

The goal of this work was to define the contributions of intrinsic and synaptic mechanisms toward spontaneous network-wide bursting activity, observed in dissociated rat hippocampal cell cultures. This network behavior is typically characterized by short-duration bursts, separated by order of magnitude longer interburst intervals. We hypothesize that while short-timescale synaptic processes modulate spectro-temporal intraburst properties and network-wide burst propagation, much longer timescales of intrinsic membrane properties such as persistent sodium (Nap) currents govern burst onset during interburst intervals. To test this, we used synaptic receptor antagonists picrotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP) to selectively block GABAA, AMPA, and NMDA receptors and riluzole to selectively block Nap channels. We systematically compared intracellular activity (recorded with patch clamp) and network activity (recorded with multielectrode arrays) in eight different synaptic connectivity conditions: GABAA + NMDA + AMPA, NMDA + AMPA, GABAA + AMPA, GABAA + NMDA, AMPA, NMDA, GABAA, and all receptors blocked. Furthermore, we used mixed-effects modeling to quantify the aforementioned independent and interactive synaptic receptor contributions toward spectro-temporal burst properties including intraburst spike rate, burst activity index, burst duration, power in the local field potential, network connectivity, and transmission delays. We found that blocking intrinsic Nap currents completely abolished bursting activity, demonstrating their critical role in burst onset within the network. On the other hand, blocking different combinations of synaptic receptors revealed that spectro-temporal burst properties are uniquely associated with synaptic functionality and that excitatory connectivity is necessary for the presence of network-wide bursting. In addition to confirming the critical contribution of direct excitatory effects, mixed-effects modeling also revealed distinct combined (nonlinear) contributions of excitatory and inhibitory synaptic activity to network bursting properties.

Regulation of prefrontal excitatory neurotransmission by dopamine in the nucleus accumbens core.

Interactions between dopamine and glutamate signalling within the nucleus accumbens core are required for behavioural reinforcement and habit formation. Dopamine modulates excitatory glutamatergic signals from the prefrontal cortex, but the precise mechanism has not been identified. We combined optical and electrophysiology recordings in murine slice preparations from CB1 receptor-null mice and green fluorescent protein hemizygotic bacterial artificial chromosome transgenic mice to show how dopamine regulates glutamatergic synapses specific to the striatonigral and striatopallidal basal ganglia pathways. At low cortical frequencies, dopamine D1 receptors promote glutamate release to both D1 and D2 receptor-expressing medium spiny neurons while D2 receptors specifically inhibit excitatory inputs to D2 receptor-expressing cells by decreasing exocytosis from cortical terminals with a low probability of release. At higher cortical stimulation frequencies, this dopaminergic modulation of presynaptic activity is occluded by adenosine and endocannabinoids. Glutamatergic inputs to both D1 and D2 receptor-bearing medium spiny neurons are inhibited by adenosine, released upon activation of NMDA and AMPA receptors and adenylyl cyclase in D1 receptor-expressing cells. Excitatory inputs to D2 receptor-expressing cells are specifically inhibited by endocannabinoids, whose release is dependent on D2 and group 1 metabotropic glutamate receptors. The convergence of excitatory and inhibitory modulation of corticoaccumbal activity by dopamine, adenosine and endocannabinoids creates subsets of corticoaccumbal inputs, selectively and temporally reinforces strong cortical signals through the striatonigral pathway while inhibiting the weak, and may provide a mechanism whereby continued attention might be focused on behaviourally salient information.