The impact of neuron morphology on cortical network architecture.

The neurons in the cerebral cortex are not randomly interconnected. This specificity in wiring can result from synapse formation mechanisms that connect neurons, depending on their electrical activity and genetically defined identity. Here, we report that the morphological properties of the neurons provide an additional prominent source by which wiring specificity emerges in cortical networks.

Neuroscience history interview with Professor Bert Sakmann, Nobel Laureate in Physiology or Medicine (1991), Max Planck Society, Germany.

Dr. Bert Sakmann (b. 1942) studied at the Universities of Tuebingen, Freiburg, Berlin, Paris, and Munich, graduating in 1967.

High-frequency burst spiking in layer 5 thick-tufted pyramids of rat primary somatosensory cortex encodes exploratory touch.

Diversity of cell-types that collectively shape the cortical microcircuit ensures the necessary computational richness to orchestrate a wide variety of behaviors. The information content embedded in spiking activity of identified cell-types remain unclear to a large extent. Here, we recorded spike responses upon whisker touch of anatomically identified excitatory cell-types in primary somatosensory cortex in naive, untrained rats.

A vicious cycle of β amyloid-dependent neuronal hyperactivation.

β-amyloid (Aβ)-dependent neuronal hyperactivity is believed to contribute to the circuit dysfunction that characterizes the early stages of Alzheimer's disease (AD). Although experimental evidence in support of this hypothesis continues to accrue, the underlying pathological mechanisms are not well understood. In this experiment, we used mouse models of Aβ-amyloidosis to show that hyperactivation is initiated by the suppression of glutamate reuptake.

Relationships between structure, in vivo function and long-range axonal target of cortical pyramidal tract neurons.

Pyramidal tract neurons (PTs) represent the major output cell type of the neocortex. To investigate principles of how the results of cortical processing are broadcasted to different downstream targets thus requires experimental approaches, which provide access to the in vivo electrophysiology of PTs, whose subcortical target regions are identified. On the example of rat barrel cortex (vS1), we illustrate that retrograde tracer injections into multiple subcortical structures allow identifying the long-range axonal targets of individual in vivo recorded PTs.

Anatomical Correlates of Local, Translaminar, and Transcolumnar Inhibition by Layer 6 GABAergic Interneurons in Somatosensory Cortex.

In the vibrissal area of rodent somatosensory cortex, information on whisker stimulation is processed by neuronal networks in a corresponding cortical column. To understand how sensory stimuli are represented in a column, it is essential to identify cell types constituting these networks. Layer 6 (L6) comprises 25% of all neurons in a column.

Organization and somatotopy of corticothalamic projections from L5B in mouse barrel cortex.

Neurons in cortical layer 5B (L5B) connect the cortex to numerous subcortical areas. Possibly the best-studied L5B cortico-subcortical connection is that between L5B neurons in the rodent barrel cortex (BC) and the posterior medial nucleus of the thalamus (POm). However, the spatial organization of L5B giant boutons in the POm and other subcortical targets is not known, and therefore it is unclear if this descending pathway retains somatotopy, i.

BACE inhibition-dependent repair of Alzheimer's pathophysiology.

Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral Aβ levels, whether it also can ameliorate neural circuit and memory impairments remains unclear.

From single cells and single columns to cortical networks: dendritic excitability, coincidence detection and synaptic transmission in brain slices and brains.

Although patch pipettes were initially designed to record extracellularly the elementary current events from muscle and neuron membranes, the whole-cell and loose cell-attached recording configurations proved to be useful tools for examination of signalling within and between nerve cells. In this Paton Prize Lecture, I will initially summarize work on electrical signalling within single neurons, describing communication between the dendritic compartments, soma and nerve terminals via forward- and backward-propagating action potentials. The newly discovered dendritic excitability endows neurons with the capacity for coincidence detection of spatially separated subthreshold inputs.

Cortical Dependence of Whisker Responses in Posterior Medial Thalamus In Vivo.

Cortical layer 5B (L5B) thick-tufted pyramidal neurons have reliable responses to whisker stimulation in anesthetized rodents. These cells drive a corticothalamic pathway that evokes spikes in thalamic posterior medial nucleus (POm). While a subset of POm has been shown to integrate both cortical L5B and paralemniscal signals, the majority of POm neurons are suggested to receive driving input from L5B only.

Corticothalamic Spike Transfer via the L5B-POm Pathway in vivo.

The cortex connects to the thalamus via extensive corticothalamic (CT) pathways, but their function in vivo is not well understood. We investigated "top-down" signaling from cortex to thalamus via the cortical layer 5B (L5B) to posterior medial nucleus (POm) pathway in the whisker system of the anesthetized mouse. While L5B CT inputs to POm are extremely strong in vitro, ongoing activity of L5 neurons in vivo might tonically depress these inputs and thereby block CT spike transfer.

Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites.

Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs.

Single-shot three-dimensional imaging of dilute atomic clouds.

Light field microscopy methods together with three-dimensional (3D) deconvolution can be used to obtain single-shot 3D images of atomic clouds. We demonstrate the method using a test setup that extracts 3D images from a fluorescent Rb87 atomic vapor.

Parameters predicting follicular carcinoma in thyroid nodules with indeterminate cytology.

Aim: To determine the parameters supporting the malignancy by comparing demographic features of patients and nodule features in malign and benign nodules according to the pathology results after thyroidectomy in patients with the suspicious fine needle aspiration biopsy (FNAB) results for follicular neoplasia.

Material And Method: Thyroidectomy performed 152 cases with the suspicion of follicular carcinoma owing to the FNAB results were included in the study. Age, radiation exposure history, and serum TSH levels of patients were recorded as well as the ultrasound findings of nodules as nodule count, diameter, internal structure, echogenicity, border features, presence of peripheral halo, and presence of internal micro calcifications.

Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator.

In vivo Ca2+ imaging of neuronal populations in deep cortical layers has remained a major challenge, as the recording depth of two-photon microscopy is limited because of the scattering and absorption of photons in brain tissue. A possible strategy to increase the imaging depth is the use of red-shifted fluorescent dyes, as scattering of photons is reduced at long wavelengths. Here, we tested the red-shifted fluorescent Ca2+ indicator Cal-590 for deep tissue experiments in the mouse cortex in vivo.

Beyond Columnar Organization: Cell Type- and Target Layer-Specific Principles of Horizontal Axon Projection Patterns in Rat Vibrissal Cortex.

Vertical thalamocortical afferents give rise to the elementary functional units of sensory cortex, cortical columns. Principles that underlie communication between columns remain however unknown. Here we unravel these by reconstructing in vivo-labeled neurons from all excitatory cell types in the vibrissal part of rat primary somatosensory cortex (vS1).

Synaptic Conductance Estimates of the Connection Between Local Inhibitor Interneurons and Pyramidal Neurons in Layer 2/3 of a Cortical Column.

Stimulation of a principal whisker yields sparse action potential (AP) spiking in layer 2/3 (L2/3) pyramidal neurons in a cortical column of rat barrel cortex. The low AP rates in pyramidal neurons could be explained by activation of interneurons in L2/3 providing inhibition onto L2/3 pyramidal neurons. L2/3 interneurons classified as local inhibitors based on their axonal projection in the same column were reported to receive strong excitatory input from spiny neurons in L4, which are also the main source of the excitatory input to L2/3 pyramidal neurons.

Linear integration of spine Ca2+ signals in layer 4 cortical neurons in vivo.

Sensory information reaches the cortex through synchronously active thalamic axons, which provide a strong drive to layer 4 (L4) cortical neurons. Because of technical limitations, the dendritic signaling processes underlying the rapid and efficient activation of L4 neurons in vivo remained unknown. Here we introduce an approach that allows the direct monitoring of single dendritic spine Ca(2+) signals in L4 spiny stellate cells of the vibrissal mouse cortex in vivo.

Contribution of intracolumnar layer 2/3-to-layer 2/3 excitatory connections in shaping the response to whisker deflection in rat barrel cortex.

This computational study integrates anatomical and physiological data to assess the functional role of the lateral excitatory connections between layer 2/3 (L2/3) pyramidal cells (PCs) in shaping their response during early stages of intracortical processing of a whisker deflection (WD). Based on in vivo and in vitro recordings, and 3D reconstructions of connected pairs of L2/3 PCs, our model predicts that: 1) AMPAR and NMDAR conductances/synapse are 0.52 ± 0.

Multibranch activity in basal and tuft dendrites during firing of layer 5 cortical neurons in vivo.

Layer 5 pyramidal neurons process information from multiple cortical layers to provide a major output of cortex. Because of technical limitations it has remained unclear how these cells integrate widespread synaptic inputs located in distantly separated basal and tuft dendrites. Here, we obtained in vivo two-photon calcium imaging recordings from the entire dendritic field of layer 5 motor cortex neurons.

Reactivation of the same synapses during spontaneous up states and sensory stimuli.

In the mammalian brain, calcium signals in dendritic spines are involved in many neuronal functions, particularly in the induction of synaptic plasticity. Recent studies have identified sensory stimulation-evoked spine calcium signals in cortical neurons in vivo. However, spine signaling during ongoing cortical activity in the absence of sensory input, which is essential for important functions like memory consolidation, is not well understood.

Spontaneous persistent activity in entorhinal cortex modulates cortico-hippocampal interaction in vivo.

Persistent activity is thought to mediate working memory during behavior. Can it also occur during sleep? We found that the membrane potential of medial entorhinal cortex layer III (MECIII) neurons, a gateway between neocortex and hippocampus, showed spontaneous, stochastic persistent activity in vivo in mice during Up-Down state oscillations (UDS). This persistent activity was locked to the neocortical Up states with a short delay, but persisted over several cortical UDS cycles.

How suitable is the measurement of take-off forces for detection of sticking during direct compression of various ibuprofen tablet formulations?

Sticking of tablet formulations to punch surfaces is one of the most common problems observed during tablet manufacture. An inline method proposed for detection of sticking during compression is the measurement of take-off forces, which occur when tablets are detached from the lower punch surface. It has been postulated that the tablet take-off force is a direct indicator of the sticking tendency of a tablet formulation.

How an interacting many-body system tunnels through a potential barrier to open space.

The tunneling process in a many-body system is a phenomenon which lies at the very heart of quantum mechanics. It appears in nature in the form of α-decay, fusion and fission in nuclear physics, and photoassociation and photodissociation in biology and chemistry. A detailed theoretical description of the decay process in these systems is a very cumbersome problem, either because of very complicated or even unknown interparticle interactions or due to a large number of constituent particles.