Biomedical subjects

Gilad Silberberg

Publications and source records attributed to Gilad Silberberg.

11 recordsLinked to original sources

PubMed2006

Morphological, electrophysiological, and synaptic properties of corticocallosal pyramidal cells in the neonatal rat neocortex.

Neocortical pyramidal cells (PCs) project to various cortical and subcortical targets. In layer V, the population of thick tufted PCs (TTCs) projects to subcortical targets such as the tectum, brainstem, and spinal cord. Another population of layer V PCs projects via the corpus callosum to the contralateral neocortical hemisphere mediating information transfer between the hemispheres. This subpopulation (corticocallosally projecting cells [CCPs]) has been previously described in terms of their morphological properties, but less is known about their electrophysiological properties, and their synaptic connectivity is unknown. We studied the morphological, electrophysiological, and synaptic properties of CCPs by retrograde labeling with fluorescent microbeads in P13-P16 Wistar rats. CCPs were characterized by shorter, untufted apical dendrites, which reached only up to layers II/III, confirming previous reports. Synaptic connections between CCPs were different from those observed between TTCs, both in probability of occurrence and dynamic properties. We found that the CCP network is about 4 times less interconnected than the TTC network and the probability of release is 24% smaller, resulting in a more linear synaptic transmission. The study shows that layer V pyramidal neurons projecting to different targets form subnetworks with specialized connectivity profiles, in addition to the specialized morphological and electrophysiological intrinsic properties.

Action Potentials↗

PubMed2006

The involvement of ErbB4 with schizophrenia: association and expression studies.

Neuregulin 1 (NRG1) has been found to be associated with schizophrenia in several populations. Consistently, mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. These observations raised the hypothesis that impaired NRG1-ErbB4 signaling may contribute to schizophrenia susceptibility. Nineteen SNPs encompassing the ErbB4 gene were selected from the HapMap database and genotyped in genomic DNA isolated from 59 Ashkenazi schizophrenia patients and 130 matched controls. Expression analysis of ErbB4 splice variants was performed on postmortem DLPFC samples obtained from Caucasian patients and controls by real-time PCR. We found a highly significant difference between patient and control groups in three SNPs from one linkage disequilibrium (LD) block both in allele (P = 0.013, 0.0045, 0.0049) and genotype frequencies (P = 0.00013, 0.000021, 0.00018), as well as a risk haplotype (P = 0.00044). Expression analysis indicated that the CYT-1 isoform is overexpressed in patients (P = 0.047) and that juxtamembrane (JM)-a displays a similar trend (P = 0.081). This study provides a direct link between ErbB4 and the disease. We propose that NRG1 and its receptor ErbB4 are components of a biological pathway, involved in the pathophysiology of schizophrenia.

Adolescent↗

PubMed2005

The neocortical microcircuit as a tabula rasa.

The neocortex has a high capacity for plasticity. To understand the full scope of this capacity, it is essential to know how neurons choose particular partners to form synaptic connections. By using multineuron whole-cell recordings and confocal microscopy we found that axons of layer V neocortical pyramidal neurons do not preferentially project toward the dendrites of particular neighboring pyramidal neurons; instead, axons promiscuously touch all neighboring dendrites without any bias. Functional synaptic coupling of a small fraction of these neurons is, however, correlated with the existence of synaptic boutons at existing touch sites. These data provide the first direct experimental evidence for a tabula rasa-like structural matrix between neocortical pyramidal neurons and suggests that pre- and postsynaptic interactions shape the conversion between touches and synapses to form specific functional microcircuits. These data also indicate that the local neocortical microcircuit has the potential to be differently rewired without the need for remodeling axonal or dendritic arbors.

Animals↗

PubMed2005

Short-term synaptic plasticity orchestrates the response of pyramidal cells and interneurons to population bursts.

The synaptic drive from neuronal populations varies considerably over short time scales. Such changes in the pre-synaptic rate trigger many temporal processes absent under steady-state conditions. This paper examines the differential impact of pyramidal cell population bursts on post-synaptic pyramidal cells receiving depressing synapses, and on a class of interneuron that receives facilitating synapses. In experiment a significant shift of the order of one hundred milliseconds is seen between the response of these two cell classes to the same population burst. It is demonstrated here that such a temporal differentiation of the response can be explained by the synaptic and membrane properties without recourse to elaborate cortical wiring schemes. Experimental data is first used to construct models of the two types of dynamic synaptic response. A population-based approach is then followed to examine analytically the temporal synaptic filtering effects of the population burst for the two post-synaptic targets. The peak-to-peak delays seen in experiment can be captured by the model for experimentally realistic parameter ranges. It is further shown that the temporal separation of the response is communicated in the outgoing action potentials of the two post-synaptic cells: pyramidal cells fire at the beginning of the burst and the class of interneuron receiving facilitating synapses fires at the end of the burst. The functional role of such delays in the temporal organisation of activity in the cortical microcircuit is discussed.

Action Potentials↗

PubMed2005

Microcircuits in action--from CPGs to neocortex.

To understand the interface between global brain function and molecular neuroscience--that is, the microcircuit level--a major challenge. Such understanding is prerequisite if we are to account for neural function in cellular terms. Very few vertebrate microcircuits are yet understood because their analysis is demanding technically. In this review of the TINS Microcircuits Special Feature, we attempt to shed light on the problem by comparing the operation of four types of microcircuit, to identify common molecular and cellular components. Central pattern generator (CPG) networks underlying rhythmic movements and hippocampal microcircuits that generate gamma and theta rhythms are compared with the neocortical microcircuits used in cognitive tasks and a cerebellar network. The long-term goal is to identify the components of a molecular and synaptic tool kit for the design of different microcircuits.

Animals↗

PubMed2005

Synaptic pathways in neural microcircuits.

The functions performed by different neural microcircuits depend on the anatomical and physiological properties of the various synaptic pathways connecting neurons. Neural microcircuits across various species and brain regions are similar in terms of their repertoire of neurotransmitters, their synaptic kinetics, their short-term and long-term plasticity, and the target-specificity of their synaptic connections. However, microcircuits can be fundamentally different in terms of the precise recurrent design used to achieve a specific functionality. In this review, which is part of the TINS Microcircuits Special Feature, we compare the connectivity designs in spinal, hippocampal, neocortical and cerebellar microcircuits, and discuss the different computational challenges that each microcircuit faces.

Animals↗

PubMed2004

Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat.

Whole-cell patch-clamp recordings followed by histochemical staining and single-cell RT-PCR were obtained from 180 Martinotti interneurones located in layers II to VI of the somatosensory cortex of Wistar rats (P13-P16) in order to examine their anatomical, electrophysiological and molecular properties. Martinotti cells (MCs) mostly displayed ovoid-shaped somata, bitufted dendritic morphologies, and axons with characteristic spiny boutons projecting to layer I and spreading horizontally across neighbouring columns more than 1 mm. Electron microscopic examination of MC boutons revealed that all synapses were symmetrical and most synapses (71%) were formed onto dendritic shafts. MCs were found to contact tuft, apical and basal dendrites in multiple neocortical layers: layer II/III MCs targeted mostly layer I and to a lesser degree layer II/III; layer IV MCs targeted mostly layer IV and to a lesser degree layer I; layer V and VI MCs targeted mostly layer IV and layer I and to a lesser degree the layer in which their somata was located. MCs typically displayed spike train accommodation (90%; n = 127) in response to depolarizing somatic current injections, but some displayed non-accommodating (8%) and a few displayed irregular spiking responses (2%). Some accommodating and irregular spiking MCs also responded initially with bursts (17%). Accommodating responses were found in all layers, non-accommodating mostly in upper layers and bursting mostly in layer V. Single-cell multiplex RT-PCR performed on 63 MCs located throughout layers II-VI, revealed that all MCs were somatostatin (SOM) positive, and negative for parvalbumin (PV) as well as vasoactive intestinal peptide (VIP). Calbindin (CB), calretinin (CR), neuropeptide Y (NPY) and cholecystokinin (CCK) were co- expressed with SOM in some MCs. Some layer-specific trends seem to exist. Finally, 24 accommodating MCs were examined for the expression of 26 ion channel genes. The ion channels with the highest expression in these MCs were (from highest to lowest); Cabeta1, Kv3.3, HCN4, Cabeta4, Kv3.2, Kv3.1, Kv2.1, HCN3, Caalpha1G, Kv3.4, Kv4.2, Kv1.1 and HCN2. In summary, this study provides the first detailed analysis of the anatomical, electrophysiological and molecular properties of Martinotti cells located in different neocortical layers. It is proposed that MCs are crucial interneurones for feedback inhibition in and between neocortical layers and columns.

Action Potentials↗

PubMed2004

Synaptic dynamics control the timing of neuronal excitation in the activated neocortical microcircuit.

It is well established that sensory stimulation results in the activity of multiple functional columns in the neocortex. The manner in which neurones within each column are active in relation to each other is, however, not known. Multiple whole-cell recordings in activated neocortical slices from rat revealed diverse correlation profiles of excitatory synaptic input to different types of neurones. The specific correlation profile between any two neurones could be predicted by the settings of synaptic depression and facilitation at the input synapses. Simulations further showed that patterned activity is essential for synaptic dynamics to impose the temporal dispersion of excitatory input. We propose that synaptic dynamics choreograph neuronal activity within the neocortical microcircuit in a context-dependent manner.

Animals↗

PubMed2004

Interneurons of the neocortical inhibitory system.

Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80% of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.

Animals↗

PubMed2003

Deriving physical connectivity from neuronal morphology.

A model is presented that allows prediction of the probability for the formation of appositions between the axons and dendrites of any two neurons based only on their morphological statistics and relative separation. Statistics of axonal and dendritic morphologies of single neurons are obtained from 3D reconstructions of biocytin-filled cells, and a statistical representation of the same cell type is obtained by averaging across neurons according to the model. A simple mathematical formulation is applied to the axonal and dendritic statistical representations to yield the probability for close appositions. The model is validated by a mathematical proof and by comparison of predicted appositions made by layer 5 pyramidal neurons in the rat somatosensory cortex with real anatomical data. The model could be useful for studying microcircuit connectivity and for designing artificial neural networks.

Animals↗

PubMed2002

Stereotypy in neocortical microcircuits.

A central debate regarding neocortical function concerns the degree to which the underlying microcircuitry is stereotypically organized. Stereotypy reflects invariance in structure and function, as a result of common genetic templates and environmental conditions, whereas uniqueness can be caused by genetic variations, differences in environmental conditions as well as random processes. Stereotypy is an appealing concept because it provides strong support for determinism in the formation of neuronal microcircuits and in the relationship between their specific structure and function.

Animals↗