Site-dependent shaping of field potential waveforms.

The activity of neuron populations gives rise to field potentials (FPs) that extend beyond the sources. Their mixing in the volume dilutes the original temporal motifs in a site-dependent manner, a fact that has received little attention. And yet, it potentially rids of physiological significance the time-frequency parameters of individual waves (amplitude, phase, duration). This is most likely to happen when a single source or a local origin is erroneously assumed. Recent studies using spatial treatment of these signals and anatomically realistic modeling of neuron aggregates provide convincing evidence for the multisource origin and site-dependent blend of FPs. Thus, FPs generated in primary structures like the neocortex and hippocampus reach far and cross-contaminate each other but also, they add and even impose their temporal traits on distant regions. Furthermore, both structures house neurons that act as spatially distinct (but overlapped) FP sources whose activation is state, region, and time dependent, making the composition of so-called local FPs highly volatile and strongly site dependent. Since the spatial reach cannot be predicted without source geometry, it is important to assess whether waveforms and temporal motifs arise from a single source; otherwise, those from each of the co-active sources should be sought.

Local and Volume-Conducted Contributions to Cortical Field Potentials.

Brain field potentials (FPs) can reach far from their sources, making difficult to know which waves come from where. We show that modern algorithms efficiently segregate the local and remote contributions to cortical FPs by recovering the generator-specific spatial voltage profiles. We investigated experimentally and numerically the local and remote origin of FPs in different cortical areas in anesthetized rats. All cortices examined show significant state, layer, and region dependent contribution of remote activity, while the voltage profiles help identify their subcortical or remote cortical origin. Co-activation of different cortical modules can be discriminated by the distinctive spatial features of the corresponding profiles. All frequency bands contain remote activity, thus influencing the FP time course, in cases drastically. The reach of different FP patterns is boosted by spatial coherence and curved geometry of the sources. For instance, slow cortical oscillations reached the entire brain, while hippocampal theta reached only some portions of the cortex. In anterior cortices, most alpha oscillations have a remote origin, while in the visual cortex the remote theta and gamma even surpass the local contribution. The quantitative approach to local and distant FP contributions helps to refine functional connectivity among cortical regions, and their relation to behavior.

A Pool of Postnatally Generated Interneurons Persists in an Immature Stage in the Olfactory Bulb.

Calretinin (CR)-expressing periglomerular (PG) cells are the most abundant interneurons in the glomerular layer of the olfactory bulb. They are predominately generated postnatally from the septal and dorsal subventricular zones that continue producing them well into adulthood. Yet, little is known about their properties and functions. Using transgenic approaches and patch-clamp recording in mice of both sexes we show that CR(+) PG cells of both septal and dorsal origin have homogeneous morphological and electrophysiological properties. However, unlike other PG cells, these axonless neurons express a surprisingly small repertoire of voltage-activated channels and do not fire or fire at most a single and often small action potential. Moreover, they are not innervated by olfactory sensory neurons and receive little synaptic inputs from mitral or tufted cells at excitatory synapses where NMDA receptors predominate. These membrane and synaptic properties, that resemble those of newborn immature neurons not yet integrated in the network, persist over time and limit the recruitment of CR(+) PG cells by afferent inputs that strongly drive local network activity. Together, our results show that postnatally generated CR(+) PG cells continuously supply a large pool of neurons with unconventional properties. These data also question the contribution of CR(+) PG cells in olfactory bulb computation.SIGNIFICANCE STATEMENT Calretinin-expressing PG cells are by far the most abundant interneurons in the glomerular layer of the olfactory bulb. They are continuously produced during postnatal life, including adulthood, from neural stem cells located in the subventricular zones. Surprisingly, unlike other postnatally generated newborn neurons that quickly integrate into preexisting olfactory bulb networks, calretinin-expressing PG cells retain immature properties that limit their recruitment in local network activity for weeks, if not months, as if they would never fully mature. The function of this so far unsuspected pool of latent neurons is still unknown.

Diversity of LFPs Activated in Different Target Regions by a Common CA3 Input.

Identifying the pathways contributing to local field potential (LFP) events and oscillations is essential to determine whether synchronous interregional patterns indicate functional connectivity. Here, we studied experimentally and numerically how different target structures receiving input from a common population shape their LFPs. We focused on the bilateral CA3 that sends gamma-paced excitatory packages to the bilateral CA1, the lateral septum, and itself (recurrent input). The CA3-specific contribution was isolated from multisite LFPs in target regions using spatial discrimination techniques. We found strong modulation of LFPs by target-specific features, including the morphology and population arrangement of cells, the timing of CA3 inputs, volume conduction from nearby targets, and co-activated inhibition. Jointly they greatly affect the LFP amplitude, profile, and frequency characteristics. For instance, ipsilateral (Schaffer) LFPs occluded contralateral ones, and septal LFPs arise mostly from remote sources while local contribution from CA3 input was minor. In the CA3 itself, gamma waves have dual origin from local networks: in-phase excitatory and nearly antiphase inhibitory. Also, waves may have different duration and varying phase in different targets. These results indicate that to explore the cellular basis of LFPs and the functional connectivity between structures, besides identifying the origin population/s, target modifiers should be considered.

Intraglomerular lateral inhibition promotes spike timing variability in principal neurons of the olfactory bulb.

The activity of mitral and tufted cells, the principal neurons of the olfactory bulb, is modulated by several classes of interneurons. Among them, diverse periglomerular (PG) cell types interact with the apical dendrites of mitral and tufted cells inside glomeruli at the first stage of olfactory processing. We used paired recording in olfactory bulb slices and two-photon targeted patch-clamp recording in vivo to characterize the properties and connections of a genetically identified population of PG cells expressing enhanced yellow fluorescent protein (EYFP) under the control of the Kv3.1 potassium channel promoter. Kv3.1-EYFP(+) PG cells are axonless and monoglomerular neurons that constitute ∼30% of all PG cells and include calbindin-expressing neurons. They respond to an olfactory nerve stimulation with a short barrage of excitatory inputs mediated by mitral, tufted, and external tufted cells, and, in turn, they indiscriminately release GABA onto principal neurons. They are activated by even the weakest olfactory nerve input or by the discharge of a single principal neuron in slices and at each respiration cycle in anesthetized mice. They participate in a fast-onset intraglomerular lateral inhibition between principal neurons from the same glomerulus, a circuit that reduces the firing rate and promotes spike timing variability in mitral cells. Recordings in other PG cell subtypes suggest that this pathway predominates in generating glomerular inhibition. Intraglomerular lateral inhibition may play a key role in olfactory processing by reducing the similarity of principal cells discharge in response to the same incoming input.

The real-life value of ST2 monitoring during heart failure decompensation: impact on long-term readmission and mortality.

CONTEXT: Prognostic value of ST2 levels and dynamics has not been investigated in acute heart failure (AHF) using prospective real-life measurements. OBJECTIVE: The objective of this study is to investigate the prognostic value of ST2 in AHF. METHODS: ST2 levels were determined at admission (n = 182) and discharge (n = 85). Primary endpoint was the composite of all-cause death and HF rehospitalisation at one year. RESULTS: Discharge ST2 (HR 2.42 [95% CI 1.46-4], p = 0.001) and ΔST2 (HR 2.32 [95% CI 1.21-4.57], p = 0.01) but not admission ST2, remained independently prognostic for the primary endpoint after comprehensive multivariable adjustment. ST2 significantly improved prognosis stratification on top of clinical variables and NTproBNP. CONCLUSIONS: Routine clinical use of discharge ST2 and ST2 dynamics provide independent prognostic information.

Schaffer-specific local field potentials reflect discrete excitatory events at gamma frequency that may fire postsynaptic hippocampal CA1 units.

Information processing and exchange between brain nuclei are made through spike series sent by individual neurons in highly irregular temporal patterns. Synchronization in cell assemblies, proposed as a network language for internal neural representations, still has little experimental support. We use a novel technique to extract pathway-specific local field potentials (LFPs) in the hippocampus to explore the ongoing temporal structure of a single presynaptic input, the CA3 Schaffer pathway, and its contribution to the spontaneous output of CA1 units in anesthetized rat. We found that Schaffer-specific LFPs are composed of a regular succession of pulse-like excitatory packages initiated by spontaneous clustered firing of CA3 pyramidal cells to which individual units contribute variably. A fraction of these packages readily induce firing of CA1 pyramidal cells and interneurons, the so-called Schaffer-driven spikes, revealing the presynaptic origin in the output code of single CA1 units. The output of 70% of CA1 pyramidal neurons contains up to 10% of such spikes. Our results suggest a hierarchical internal operation of the CA3 region based on sequential oscillatory activation of pyramidal cell assemblies whose activity partly gets in the output code at the next station. We conclude that CA1 output may directly reflect the activity of specific ensembles of CA3 neurons. Thus, the fine temporal structure of pathway-specific LFPs, as an accurate readout of the activity of a presynaptic population, is useful in searching for hidden presynaptic code in irregular spikes series of individual neurons and assemblies.

Diabetes Mellitus and Obesity as Prognostic Factors in Arthroscopic Repair of Chronic Rotator Cuff Tears.

Metabolic diseases such as obesity and diabetes mellitus seem to have an influence on reoperation and long-term functional outcomes after arthroscopic repair of chronic rotator cuff tears. High prevalence of these pathologies can be found in the Canary Islands. A retrospective cohort study was carried out, in which 80 patients undergoing shoulder arthroscopic surgery for the repair of chronic rotator cuff tears were included, with a minimum follow up of 5 years, to study the occurrence of complications, reoperation, and functional outcomes. Functionality after surgery improved in 75% of patients with diabetes and remained the same or worsened in 25% (OR = 1.444). In the group of non-diabetic patients, 83.9% had improved function after surgery while it remained the same or worsened in 16.1% (OR = 0.830). Functionality after surgery improved in 76.6% of obese patients and remained the same or worsened in 23.4% (OR = 1.324). In the non-obese group, 87.9% had improved function after surgery, while it remained the same or worsened in 12.1% (OR = 0.598). Despite not obtaining statistically significant differences, the analysis of the results obtained suggests that obesity and diabetes could act by decreasing the subjective improvement in functionality after surgery, and, in the case of obesity, also increase the risk of reoperation.

Modified Dynamic Anterior Stabilization and Labroplasty for Anterior Shoulder Instability With Concomitant SLAP Lesion.

Several arthroscopic techniques to treat anterior shoulder instability have been described. Bankart repair may be insufficient in cases with some degree of bone loss, and arthroscopic Latarjet is technically challenging. It is not rare to find at the time of surgery a more extensive labral tear (SLAP lesion) or an insufficient anterior capsulolabral tissue. We describe for those cases a dynamic anterior stabilization where using the long head of the biceps we are treating the SLAP lesion and at the same time it provides the "sling effect" of a Latarjet procedure for the anterior instability.

Treatment of Trochanteric Hip Fractures with Cephalomedullary Nails: Single Head Screw vs. Dual Integrated Compression Screw Systems.

Extracapsular hip fractures are very common in the elderly. They are mainly treated surgically with an intramedullary nail. Nowadays, both endomedullary hip nails with single cephalic screw systems and interlocking double screw systems are available on the market. The latter are supposed to increase rotational stability and therefore decrease the risk of collapse and cut-out. A retrospective cohort study was carried out, in which 387 patients with extracapsular hip fracture undergoing internal fixation with an intramedullary nail were included to study the occurrence of complications and reoperations. Of the 387 patients, 69% received a single head screw nail and 31% received a dual integrated compression screw nail. The median follow-up was 1.1 years, and in that time, a total of 17 reoperations were performed (4.2%; 2.1% for single head screw nails vs. 8.7% for double head screws). According to the multivariate logistic regression model adjusted for age, sex and basicervical fracture, the adjusted hazard risk of reoperation required was 3.6 times greater when using double interlocking screw systems (p = 0.017). A propensity scores analysis confirmed this finding. In conclusion, despite the potential benefits of using two interlocking head screw systems and the increased risk of reoperation in our single center, we encourage to other researchers to explore this question in a wider multicenter study.

The right hippocampus leads the bilateral integration of gamma-parsed lateralized information.

It is unclear whether the two hippocampal lobes convey similar or different activities and how they cooperate. Spatial discrimination of electric fields in anesthetized rats allowed us to compare the pathway-specific field potentials corresponding to the gamma-paced CA3 output (CA1 Schaffer potentials) and CA3 somatic inhibition within and between sides. Bilateral excitatory Schaffer gamma waves are generally larger and lead from the right hemisphere with only moderate covariation of amplitude, and drive CA1 pyramidal units more strongly than unilateral waves. CA3 waves lock to the ipsilateral Schaffer potentials, although bilateral coherence was weak. Notably, Schaffer activity may run laterally, as seen after the disruption of the connecting pathways. Thus, asymmetric operations promote the entrainment of CA3-autonomous gamma oscillators bilaterally, synchronizing lateralized gamma strings to converge optimally on CA1 targets. The findings support the view that interhippocampal connections integrate different aspects of information that flow through the left and right lobes.

Carbamazepine modulates the spatiotemporal activity in the dentate gyrus of rats and pharmacoresistant humans in vitro.

INTRODUCTION: Human hippocampal tissue resected from pharmacoresistant epilepsy patients was investigated to study the effect of the antiepileptic drug CBZ (carbamazepine) and was compared to similar experiments in the hippocampus of control rats. METHODS: The molecular layer of the DG (dentate gyrus) of human epileptic tissue and rat nonepileptic tissue was electrically stimulated and the evoked responses were recorded with voltage-sensitive dye imaging to characterize the spatiotemporal properties. RESULTS: Bath applied CBZ (100 µmol/L) reduced the amplitude of the evoked responses in the human DG, albeit that no clear use-dependent effects were found at frequencies of 8 or 16 Hz. In nonepileptic control DG from rats, CBZ also reduced the amplitude of the evoked response in the molecular layer of the DG as well as the spatial extent of the response. CONCLUSIONS: This study demonstrates that CBZ still reduced the activity in the DG, although the patients were clinically diagnosed as pharmacoresistant for CBZ. This suggests that in the human epileptic brain, the targets of CBZ, the voltage-gated Na(+) channels, are still sensitive to CBZ, although we used a relative high concentration and it is not possibility to assess the actual CBZ concentration that reached the target in the patient. We also concluded that the effect of CBZ was found in the activated region of the DG, quite comparable to the observations in the nonepileptic rat.

Parallel readout of pathway-specific inputs to laminated brain structures.

Local field potentials (LFPs) capture the electrical activity produced by principal cells during integration of converging synaptic inputs from multiple neuronal populations. However, since synaptic currents mix in the extracellular volume, LFPs have complex spatiotemporal structure, making them hard to exploit. Here we propose a biophysical framework to identify and separate LFP-generators. First we use a computational multineuronal model that scales up single cell electrogenesis driven by several synaptic inputs to realistic aggregate LFPs. This approach relies on the fixed but distinct locations of synaptic inputs from different presynaptic populations targeting a laminated brain structure. Thus the LFPs are contributed by several pathway-specific LFP-generators, whose electrical activity is defined by the spatial distribution of synaptic terminals and the time course of synaptic currents initiated in target cells by the corresponding presynaptic population. Then we explore the efficacy of independent component analysis to blindly separate converging sources and reconstruct pathway-specific LFP-generators. This approach can optimally locate synaptic inputs with subcellular accuracy while the reconstructed time course of pathway-specific LFP-generators is reliable in the millisecond scale. We also describe few cases where the non-linear intracellular interaction of strongly overlapping LFP-generators may lead to a significant cross-contamination and the appearance of derivative generators. We show that the approach reliably disentangle ongoing LFPs in the hippocampus into contribution of several LFP-generators. We were able to readout in parallel the pathway-specific presynaptic activity of projection cells in the entorhinal cortex and pyramidal cells in the ipsilateral and contralateral CA3. Thus we provide formal mathematical and experimental support for parallel readout of the activity of converging presynaptic populations in working neuronal circuits from common LFPs.

Easily made single-walled carbon nanotube surface microelectrodes for neuronal applications.

The present work examines the feasibility of a simple method for using single-walled carbon nanotubes (SWNT) to fabricate multielectrode arrays (MEA) for electrophysiological recordings. A suspension of purified SWNTs produced by arc discharged was directly deposited onto standard platinum electrodes. The in vitro impedance and electrochemical characterizations demonstrated the enhanced electrical properties of the SWNT microelectrode array. To test its functionality we performed extracellular ganglion cell recordings in isolated superfused rabbit retinas. Our results showed that SWNT based electrode arrays have potential advantages over metal electrodes and can be successfully used to record the single and multi-unit activity of ganglion cell populations.