Potential Synapses Research Articles

Skyrmion-based racetrack multilevel data storage device manipulated by pinning

Magnetic skyrmions are particle-like topological protected spin structures that can be driven by electric current. We demonstrate a single skyrmion-based multilevel data storage device that could also work as the potential artificial synapse for neuromorphic computing. Four pinning sites are designed to situate the skyrmion in selective regions, whose resistances rise owing to the anisotropic magnetoresistance (AMR) induced by the skyrmion. Skyrmion’s position could denote the data levels when the device works as a multilevel data storage device. Pinning sites’ positions represent the synaptic weights when it functions as the artificial synapse. Multilevel data storage device’s data level change or the synapse’s potentiation and depression is realized by the electric current applied parallel to the track. Our work shows that the AMR could help to detect a single skyrmion without the magnetic tunnel junction. Moreover, the skyrmion manipulated by pinning provides an approach for precise control and helps realize skyrmion-based in-memory computing.

Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma.

The incidence of head and neck squamous cell carcinoma (HNSC) is increasing year by year. The nerve is an important component of the tumor microenvironment, which has a wide range of cross-talk with tumor cells and immune cells, especially in highly innervated organs, such as head and neck cancer and pancreatic cancer. However, the role of cancer-nerve cross-talk-related genes (NCCGs) in HNSC is unclear. In our study, we constructed a prognostic model based on genes with prognostic value in NCCGs. We used Pearson’s correlation to analyze the relationship between NCCGs and immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. We used single-cell sequencing data to analyze the expression of genes associated with stage in different cells and explored the possible pathways affected by these genes via gene set enrichment analysis. In the TCGA-HNSC cohort, a total of 23 genes were up- or downregulated compared with normal tissues. GO and KEGG pathway analysis suggested that NCCGs are mainly concentrated in membrane potential regulation, chemical synapse, axon formation, and neuroreceptor-ligand interaction. Ten genes were identified as prognosis genes by Kaplan-Meier plotter and used as candidate genes for LASSO regression. We constructed a seven-gene prognostic model (NTRK1, L1CAM, GRIN3A, CHRNA5, CHRNA6, CHRNB4, CHRND). The model could effectively predict the 1-, 3-, and 5-year survival rates in the TCGA-HNSC cohort, and the effectiveness of the model was verified by external test data. The genes included in the model were significantly correlated with immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. Single-cell sequencing data of HNSC showed that CHRNB4 was mainly expressed in tumor cells, and multiple metabolic pathways were enriched in high CHRNB4 expression tumor cells. In summary, we used comprehensive bioinformatics analysis to construct a prognostic gene model and revealed the potential of NCCGs as therapeutic targets and prognostic biomarkers in HNSC.

Dual-Cell Patch-Clamp Recording Revealed a Mechanism for a Ribbon Synapse to Process Both Digital and Analog Inputs and Outputs.

A chemical synapse is either an action potential (AP) synapse or a graded potential (GP) synapse but not both. This study investigated how signals passed the glutamatergic synapse between the rod photoreceptor and its postsynaptic hyperpolarizing bipolar cells (HBCs) and light responses of retinal neurons with dual-cell and single-cell patch-clamp recording techniques. The results showed that scotopic lights evoked GPs in rods, whose depolarizing Phase 3 associated with the light offset also evoked APs of a duration of 241.8 ms and a slope of 4.5 mV/ms. The depolarization speed of Phase 3 (Speed) was 0.0001–0.0111 mV/ms and 0.103–0.469 mV/ms for rods and cones, respectively. On pairs of recorded rods and HBCs, only the depolarizing limbs of square waves applied to rods evoked clear currents in HBCs which reversed at −6.1 mV, indicating cation currents. We further used stimuli that simulated the rod light response to stimulate rods and recorded the rod-evoked excitatory current (rdEPSC) in HBCs. The normalized amplitude (R/Rmax), delay, and rising slope of rdEPSCs were differentially exponentially correlated with the Speed (all p < 0.001). For the Speed < 0.1 mV/ms, R/Rmax grew while the delay and duration reduced slowly; for the Speed between 0.1 and 0.4 mV/ms, R/Rmax grew fast while the delay and duration dramatically decreased; for the Speed > 0.4 mV/ms, R/Rmax reached the plateau, while the delay and duration approached the minimum, resembling digital signals. The rdEPSC peak was left-shifted and much faster than currents in rods. The scotopic-light-offset-associated major and minor cation currents in retinal ganglion cells (RGCs), the gigantic excitatory transient currents (GTECs) in HBCs, and APs and Phase 3 in rods showed comparable light-intensity-related locations. The data demonstrate that the rod-HBC synapse is a perfect synapse that can differentially decode and code analog and digital signals to process enormously varied rod and coupled-cone inputs.

Imaging Transplanted Photoreceptors in Living Nonhuman Primates with Single-Cell Resolution.

SummaryStem cell-based transplantation therapies offer hope for currently untreatable retinal degenerations; however, preclinical progress has been largely confined to rodent models. Here, we describe an experimental platform for accelerating photoreceptor replacement therapy in the nonhuman primate, which has a visual system much more similar to the human. We deployed fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO) to noninvasively track transplanted photoreceptor precursors over time at cellular resolution in the living macaque. Fluorescently labeled photoreceptors generated from a CRX+/tdTomato human embryonic stem cell (hESC) reporter line were delivered subretinally to macaques with normal retinas and following selective ablation of host photoreceptors using an ultrafast laser. The fluorescent reporter together with FAOSLO allowed transplanted photoreceptor precursor survival, migration, and neurite formation to be monitored over time in vivo. Histological examination suggested migration of photoreceptor precursors to the outer plexiform layer and potential synapse formation in ablated areas in the macaque eye.

Effect of Amlodipine to MAP2 on Neurons Culture SH-SY5Y That Induced by Chronic Hyperglycemia

Exposure to chronic hyperglycemia in neurons results in increased Ca2+ intracellular then causes increased oxidative stress. Oxidative stress will increase the activity of calcium activated neural protease causing MAP2 (microtubule associated protein 2) to decrease which will increase the cell death. The aim of research is to determine on the effects of amlodipine on the expression of MAP2 in SH-SY5Y neuron culture cells. This research is an experimental study, using SH-SY5Y neuron cell culture and then exposed to hyperglycemia for 6 days, then given amlodipine 10 nM and 100 nM. Then the MAP2 expression is seen. Based on the results of the Anova test on the administration of 10 nM, 100 nM and without amlodipine on the expression of MAP2 in culture of SH-SY5 neurons, which were 50 mM glucose for 6 days there was decrease in MAP2 (p = 0.082). Based on Spearman correlation test results, there was a strong relationship (p = 0.011) (r = -0.7791). There is decrease expression of the MAP2 after the administration of the dose of amlodipine 10 nM, 100 nM and without administration although not significant. It is estimated that another line activation occurs. One such pathway is the activation NMDA receptor will inhibit potential post synapse and increase calpain activation to cause a decrease in MAP2.

Synaptic Plasticity and Metaplasticity of Biological Synapse Realized in a KNbO3 Memristor for Application to Artificial Synapse.

Amorphous KNbO3 (KN) films were grown on a TiN/SiO2/Si substrate to synthesize a KN memristor as a potential artificial synapse. The Pt/KN/TiN memristor exhibited typical and reliable bipolar switching behavior with multiple resistance levels. It also showed the transmission properties of a biological synapse, with a good conductance modulation linearity. Moreover, the KN memristor can emulate various biological synaptic plasticity characteristics including short-term plasticity, long-term plasticity, spike-rate dependent plasticity, paired-pulse facilitation, and post-tetanic potentiation by controlling the number and rate of the potentiation spike. Spike-timing-dependent plasticity (STDP), which is an essential property of biological synapses, is also realized in the KN memristor. The synaptic plasticity of the KN memristor can be explained by oxygen vacancy movement and oxygen vacancy filaments. The metaplasticity of biological synapses was also implemented in the KN memristor, including the metaplasticity of long-term potentiation and depression, and of STDP. Therefore, the KN memristor could be used as an artificial synapse in neuromorphic computing systems.

Morphological Diversity Strongly Constrains Synaptic Connectivity and Plasticity.

Synaptic connectivity between neurons is naturally constrained by the anatomical overlap of neuronal arbors, the space on the axon available for synapses, and by physiological mechanisms that form synapses at a subset of potential synapse locations. What is not known is how these constraints impact emergent connectivity in a circuit with diverse morphologies. We investigated the role of morphological diversity within and across neuronal types on emergent connectivity in a model of neocortical microcircuitry. We found that the average overlap between the dendritic and axonal arbors of different types of neurons determines neuron-type specific patterns of distance-dependent connectivity, severely constraining the space of possible connectomes. However, higher order connectivity motifs depend on the diverse branching patterns of individual arbors of neurons belonging to the same type. Morphological diversity across neuronal types, therefore, imposes a specific structure on first order connectivity, and morphological diversity within neuronal types imposes a higher order structure of connectivity. We estimate that the morphological constraints resulting from diversity within and across neuron types together lead to a 10-fold reduction of the entropy of possible connectivity configurations, revealing an upper bound on the space explored by structural plasticity.

Whole-cell morphological properties of neurons constrain the nonrandom features of network connectivity

We addressed the principles of micro-level organization of neuronal circuits and explored how the neuronal morphology constrains this organization. Several studies have demonstrated the non-trivial properties of the network connectivity using in vitro recordings from multiple neurons [1-3], yet it is unclear to what extent this structure reflects reorganization caused by synaptic plasticity, and what is imposed by the morphological constraints. Two recent articles explored this issue using the simulated neural circuits and demonstrated the specific structural properties in those circuits [4,5]. We analyzed a model that emphasizes the role of single-cell morphology, a homogeneous population of neurons in a planar space without boundaries. Each neuron is composed of two displaced neurite fields defined on the limited support. A neurite field describes the likelihood of finding a neurite segment at a certain point in the plane. Using a proximity criterion (Peters' rule) the expected number of potential synapses is estimated between each pair of neurons. Alternatively, this number can be estimated from the realistic morphology of a simulated neuron, or from the morphologies reconstructed from in vitro/in vivo recordings. The number of potential synapses depends on the axon-dendrite distance, which leads to a definition of the expected radius. An axon-dendrite pair that is expected to form at least one synapse must be on a distance not larger than the effective radius. All considered statistical measures of network connectivity are expressed as the functions of the effective radius normalized with the neuron size. In this study, we considered the standard graph theoretic measures of network connectivity, the motif counts, clustering coefficient, path length, and small-world coefficient. It has been demonstrated that they have a significant impact on the population activity in simulated networks [6]. Changing the normalized effective radius from small ( 10) we vary the network properties between the two extremes. For the small values of the effective radius, the networks favor unidirectional connections and sparse local connectivity. The clustering coefficient and the path length are similar to those obtained in uniform random networks, i.e. in the networks independent of topology. For the large values of the effective radius, the local connectivity is dense with the majority of bidirectional connections. As the normalized effective radius increases, the clustering coefficient increases towards the values obtained for the networks with dominant local connectivity, while the path length remains close to the one of the uniform random networks. The normalized effective radius on the interval 1-2, provides the biggest variability of connectivity patterns and the optimized properties relevant for the information transfer.

Structural synaptic plasticity has high memory capacity and can explain graded amnesia, catastrophic forgetting, and the spacing effect.

Although already William James and, more explicitly, Donald Hebb's theory of cell assemblies have suggested that activity-dependent rewiring of neuronal networks is the substrate of learning and memory, over the last six decades most theoretical work on memory has focused on plasticity of existing synapses in prewired networks. Research in the last decade has emphasized that structural modification of synaptic connectivity is common in the adult brain and tightly correlated with learning and memory. Here we present a parsimonious computational model for learning by structural plasticity. The basic modeling units are “potential synapses” defined as locations in the network where synapses can potentially grow to connect two neurons. This model generalizes well-known previous models for associative learning based on weight plasticity. Therefore, existing theory can be applied to analyze how many memories and how much information structural plasticity can store in a synapse. Surprisingly, we find that structural plasticity largely outperforms weight plasticity and can achieve a much higher storage capacity per synapse. The effect of structural plasticity on the structure of sparsely connected networks is quite intuitive: Structural plasticity increases the “effectual network connectivity”, that is, the network wiring that specifically supports storage and recall of the memories. Further, this model of structural plasticity produces gradients of effectual connectivity in the course of learning, thereby explaining various cognitive phenomena including graded amnesia, catastrophic forgetting, and the spacing effect.

Neuronal Electrophysiological Function and Control of Neurite Outgrowth on Electrospun Polymer Nanofibers Are Cell Type Dependent

Modeling of cellular environments with nanofabricated biomaterial scaffolds has the potential to improve the growth and functional development of cultured cellular models, as well as assist in tissue engineering efforts. An understanding of how such substrates may alter cellular function is critical. Highly plastic central nervous system hippocampal cells and non-network forming peripheral nervous system dorsal root ganglion (DRG) cells from embryonic rats were cultured upon laminin-coated degradable polycaprolactone (PCL) and nondegradable polystyrene (PS) electrospun nanofibrous scaffolds with fiber diameters similar to those of neuronal processes. The two cell types displayed intrinsically different growth patterns on the nanofibrous scaffolds. Hippocampal neurites grew both parallel and perpendicular to the nanofibers, a property that would increase neurite-to-neurite contacts and maximize potential synapse development, essential for extensive network formation in a highly plastic cell type. In contrast, non-network-forming DRG neurons grew neurites exclusively along fibers, recapitulating the simple direct unbranching pathway between sensory ending and synapse in the spinal cord that occurs in vivo. In addition, the two primary neuronal types showed different functional capacities under patch clamp testing. The substrate composition did not alter the neuronal functional development, supporting electrospun PCL and PS as candidate materials for controlled cellular environments in culture and electrospun PCL for directed neurite outgrowth in tissue engineering applications.

Synaptic and extrasynaptic plasticity in glutamatergic circuits involving dentate granule cells following chronic N-methyl-D-aspartate receptor inhibition.

Chronic global N-methyl-d-aspartate receptor (NMDAR) blockade leads to changes in glutamatergic transmission. The impact of more subunit-selective NMDAR inhibition on glutamatergic circuits remains incomplete. To this end, organotypic hippocampal slice cultures were treated for 17-21 days with the high-affinity competitive antagonist d-aminophosphonovaleric acid (d-APV), the allosteric GluN2B-selective antagonist Ro25-6981, or the newer competitive GluN2A-preferring antagonist NVP-AAM077. Electrophysiological recordings from dentate granule cells revealed that chronic d-APV treatment increased, whereas chronic Ro25-6981 reduced, epileptiform event-associated large-amplitude spontaneous excitatory postsynaptic currents (sEPSC) compared with all other treatment groups, consistent with opposite effects on glutamatergic networks. Presynaptically, chronic d-APV or Ro25-6981 increased small-amplitude sEPSCs and AMPA/kainate receptor-mediated miniature EPSCs (mEPSCAMPAR) frequency. Chronic d-APV or NVP-AAM077, but not Ro25-6981, increased putative vGlut1-positive glutamatergic synapses. Postsynaptically, chronic d-APV dramatically increased mEPSCAMPAR and profoundly decreased NMDAR-mediated mEPSC (mEPSCNMDAR) measures, suggesting increased AMPAR/NMDAR ratio. Ro25-6981 decreased mEPSCAMPAR charge transfer and modestly decreased mEPSCNMDAR frequency and decay, suggesting downward scaling of AMPAR and NMDAR function without dramatically altering AMPAR/NMDAR ratio. Extrasynaptically, threo-β-benzyloxyaspartate-enhanced "tonic" NMDAR current amplitude and activated channel number estimates were significantly increased only by chronic Ro25-6981. For intrinsic excitability, action potential threshold was slightly more negative following chronic d-APV or NVP-AAM077. The predominant pro-excitatory effects of chronic d-APV are consistent with increased glutamatergic transmission and network excitability. The minor effects of chronic NVP-AAM077 on action potential threshold and synapse number are consistent with minimal effects on circuit function. The chronic Ro25-6981-induced downward scaling of synaptic AMPAR and NMDAR function is consistent with decreased postsynaptic glutamate receptors and reduced network excitability.

Vesicle release statistics at graded potential synapses: modeling study

Event Abstract Back to Event Vesicle release statistics at graded potential synapses: modeling study Mantas Gabrielaitis1, 2, 3*, Nikolai M. Chapochnikov1, 2, 3, Tobias Moser2, 3 and Fred Wolf1, 3 1 Max Planck INstitute for Dynamics and Self-Organization, Nonlinear Dynamics, Germany 2 InnerEarLab, Department of Otolaryngology, University of Goettingen Medical School, Germany 3 Bernstein Center for Computational Neuroscience, University of Goettingen, Germany Signal transfer characteristics of chemical synapses are strongly shaped by the molecular organization of the presynaptic active zone. Graded potential synapses are ubiquitous among sensory receptor neurons such as auditory and vestibular hair cells, retinal photoreceptors, and electroreceptors [1]. Generally, these synapses feature high fidelity, precision, and broad dynamic range when encoding transient or prolonged stimuli [1]. Experimental data describing the fine molecular organization of these synapses is rapidly accumulating, e.g., [2,3]. Here, we study an idealized biophysical model of the active zone of a graded potential synapse to relate its topography and molecular kinetic properties to the vesicle release dynamics. The model includes N independent Ca2+ channels described by two state Markov models. These channels can be arbitrarily distributed within the active zone along with M arbitrarily distributed vesicle docking sites. Each docking site is modeled as a two state Markov chain, one state being empty and the other - ready to release a docked vesicle. Release occurs immediately after binding of a single Ca2+ ion to the vesicle's Ca2+ sensor. The rate of binding is proportional to the calcium concentration [Ca2+] at the release site. Because Ca2+ diffusion from a channel to the release sensor is fast compared to the channel open times, we approximate [Ca2+] changes as instantaneous upon Ca2+ channel opening and closing [4]. We describe the [Ca2+] profile by a linearized buffered Ca2+ diffusion approximation [4]. Replenishment of empty docking sites occurs at constant rate. In order to characterize transient and sustained responses of this model active zone, we analyze first release event latency after a voltage step and stationary release inter-event interval distributions. We obtain analytical expressions for these quantities for various active zone topographies. By using our formalism, we examine the influence of Ca2+ channel number, positioning, and gating kinetics, vesicle docking site number and positioning, kinetics of the Ca2+ release sensor, and vesicle replenishment rate. We confirm the analytical results by direct numerical simulations. We find that, in a wide range of situations, the mean and variance of [Ca2+], and population variance of how much each channel contributes to the total [Ca2+] on average largely determine the release dynamics for a given active zone topography. For all active zone topographies, increasing number of release slots shifts the release inter-event interval statistics towards Poissonian. Increasing vesicle docking site and accompanying Ca2+ channel numbers proportionally changes the first event latency in the same way as effectively scaling the channel number. We hope that our insights on this analytically treatable model can help in analyzing how the active zone topography shapes information encoding at graded potential synapses in first approximation.

Potential Synaptic Connectivity of Different Neurons onto Pyramidal Cells in a 3D Reconstruction of the Rat Hippocampus

Most existing connectomic data and ongoing efforts focus either on individual synapses (e.g., with electron microscopy) or on regional connectivity (tract tracing). An individual pyramidal cell (PC) extends thousands of synapses over macroscopic distances (∼cm). The contrasting requirements of high-resolution and large field of view make it too challenging to acquire the entire synaptic connectivity for even a single typical cortical neuron. Light microscopy can image whole neuronal arbors and resolve dendritic branches. Analyzing connectivity in terms of close spatial appositions between axons and dendrites could thus bridge the opposite scales, from synaptic level to whole systems. In the mammalian cortex, structural plasticity of spines and boutons makes these “potential synapses” functionally relevant to learning capability and memory capacity. To date, however, potential synapses have only been mapped in the surrounding of a neuron and relative to its local orientation rather than in a system-level anatomical reference. Here we overcome this limitation by estimating the potential connectivity of different neurons embedded into a detailed 3D reconstruction of the rat hippocampus. Axonal and dendritic trees were oriented with respect to hippocampal cytoarchitecture according to longitudinal and transversal curvatures. We report the potential connectivity onto PC dendrites from the axons of a dentate granule cell, three CA3 PCs, one CA2 PC, and 13 CA3b interneurons. The numbers, densities, and distributions of potential synapses were analyzed in each sub-region (e.g., CA3 vs. CA1), layer (e.g., oriens vs. radiatum), and septo-temporal location (e.g., dorsal vs. ventral). The overall ratio between the numbers of actual and potential synapses was ∼0.20 for the granule and CA3 PCs. All potential connectivity patterns are strikingly dependent on the anatomical location of both pre-synaptic and post-synaptic neurons.

Cooperative synapse formation in the neocortex

Neuron morphology plays an important role in defining synaptic connectivity. Clearly, only pairs of neurons with closely positioned axonal and dendritic branches can be synaptically coupled. For excitatory neurons in the cerebral cortex, such axo-dendritic oppositions, termed potential synapses, must be bridged by dendritic spines to form synaptic connections. To explore the rules by which synaptic connections are formed within the constraints imposed by neuron morphology, we compared the distributions of the numbers of actual and potential synapses between pre- and postsynaptic neurons forming different laminar projections in rat barrel cortex. Quantitative comparison explicitly ruled out the hypothesis that individual synapses between neurons are formed independently of each other. Instead, the data are consistent with a cooperative scheme of synapse formation where multiple-synaptic connections between neurons are stabilized while neurons that do not establish a critical number of synapses are not likely to remain synaptically coupled.

Learning Drives Differential Clustering of Axodendritic Contacts in the Barn Owl Auditory System

Computational models predict that experience-driven clustering of coactive synapses is a mechanism for information storage. This prediction has remained untested, because it is difficult to approach through time-lapse analysis. Here, we exploit a unique feature of the barn owl auditory localization pathway that permits retrospective analysis of prelearned and postlearned circuitry: owls reared wearing prismatic spectacles develop an adaptive microcircuit that coexists with the native one but can be analyzed independently based on topographic location. To visualize the clustering of axodendritic contacts (potential synapses) within these zones, coactive axons were labeled by focal injection of fluorescent tracer and their target dendrites labeled with an antibody directed against CaMKII (calcium/calmodulin-dependent protein kinase type II, alpha subunit). Using high-resolution confocal imaging, we measured the distance from each contact to its nearest neighbor on the same branch of dendrite. We found that the distribution of intercontact distances for the adaptive zone was shifted dramatically toward smaller values compared with distributions for either the maladaptive zone of the same animals or the adaptive zone of normal juveniles, which indicates that a dynamic clustering of contacts had occurred. Moreover, clustering in the normal zone was greater in normal juveniles than in prism-adapted owls, indicative of declustering. These data demonstrate that clustering is bidirectionally adjustable and tuned by behaviorally relevant experience. The microanatomical configurations in all zones of both experimental groups matched the functional circuit strengths that were assessed by in vivo electrophysiological mapping. Thus, the observed changes in clustering are appropriately positioned to contribute to the adaptive strengthening and weakening of auditory-driven responses.

Local Potential Connectivity in Cat Primary Visual Cortex

Time invariant description of synaptic connectivity in cortical circuits may be precluded by the ongoing growth and retraction of dendritic spines accompanied by the formation and elimination of synapses. On the other hand, the spatial arrangement of axonal and dendritic branches appears stable. This suggests that an invariant description of connectivity can be cast in terms of potential synapses, which are locations in the neuropil where an axon branch of one neuron is proximal to a dendritic branch of another neuron. In this paper, we attempt to reconstruct the potential connectivity in local cortical circuits of the cat primary visual cortex (V1). Based on multiple single-neuron reconstructions of axonal and dendritic arbors in 3 dimensions, we evaluate the expected number of potential synapses and the probability of potential connectivity among excitatory (pyramidal and spiny stellate) neurons and inhibitory basket cells. The results provide a quantitative description of structural organization of local cortical circuits. For excitatory neurons from different cortical layers, we compute local domains, which contain their potentially pre- and postsynaptic excitatory partners. These domains have columnar shapes with laminar specific radii and are roughly of the size of the ocular dominance column. Therefore, connections between most excitatory neurons in the ocular dominance column can be implemented by local synaptogenesis. Structural connectivity involving inhibitory basket cells is generally weaker than excitatory connectivity. Here, only nearby neurons are capable of establishing more than one potential synapse, implying that within the ocular dominance column these connections have more limited potential for circuit remodeling.

Reliability of Signal Transfer at a Tonically Transmitting, Graded Potential Synapse of the Locust Ocellar Pathway

We assessed the performance of a synapse that transmits small, sustained, graded potentials between two classes of second-order ocellar "L-neurons" of the locust. We characterized the transmission of both fixed levels of membrane potential and fluctuating signals by recording postsynaptic responses to changes in presynaptic potential. To ensure repeatability between stimuli, we controlled presynaptic signals with a voltage clamp. We found that the synapse introduces noise above the level of background activity in the postsynaptic neuron. By driving the presynaptic neuron with slow-ramp changes in potential, we found that the number of discrete signal levels the synapse transmits is approximately 20. It can also transmit approximately 20 discrete levels when the presynaptic signal is a graded rebound spike. Synaptic noise level is constant over the operating range of the synapse, which would not be expected if presynaptic potential set the probability for the release of individual quanta of neurotransmitter according to Poisson statistics. Responses to individual quanta of neurotransmission could not be resolved, which is consistent with a synapse that operates with large numbers of vesicles evoking small responses. When challenged with white noise stimuli, the synapse can transmit information at rates up to 450 bits/s, a performance that is sufficient to transmit natural signals about changes in illumination.

Geometric and functional organization of cortical circuits

Can neuronal morphology predict functional synaptic circuits? In the rat barrel cortex, 'barrels' and 'septa' delineate an orderly matrix of cortical columns. Using quantitative laser scanning photostimulation we measured the strength of excitatory projections from layer 4 (L4) and L5A to L2/3 pyramidal cells in barrel- and septum-related columns. From morphological reconstructions of excitatory neurons we computed the geometric circuit predicted by axodendritic overlap. Within most individual projections, functional inputs were predicted by geometry and a single scale factor, the synaptic strength per potential synapse. This factor, however, varied between projections and, in one case, even within a projection, up to 20-fold. Relationships between geometric overlap and synaptic strength thus depend on the laminar and columnar locations of both the pre- and postsynaptic neurons, even for neurons of the same type. A large plasticity potential appears to be incorporated into these circuits, allowing for functional 'tuning' with fixed axonal and dendritic arbor geometry.

Information storage capacity of synaptic connectivity patterns

How much information can be encoded in synaptic connectivity patterns through formation and elimination of dendritic spines? To answer this question, we perform geometrical analysis and derive an expression for the number of potential synapses, i.e. the number of axons that pass within a spine length of a given dendrite. We evaluate this expression by using our measurements and existing anatomical data, and find that the ratio of actual to potential synapses is 0.26 in mouse neocortex, 0.18 in rat hippocampus, and 0.12–0.23 in macaque visual cortex. Consequently, mammalian synaptic connectivity patterns may encode up to 3–5 bits per synapse.

Tonic transmitter release in a graded potential synapse

1. We studied graded synaptic transmission in the fly photoreceptor-interneuron synapse by using intracellular in situ recordings from pre- and postsynaptic cells. 2. A large presynaptic hyperpolarization after light adaptation, caused by the activation of the electrogenic Na+/K+ pump, drastically reduced the conspicuous postsynaptic dark noise. At the same time, the postsynaptic neurons depolarized, with an increase of input resistance of 5-10 M omega. 3. The spectral characteristics of the postsynaptic membrane noise in dark and during noise reduction, together with the other results, suggested that the transmitter release decreased dramatically approximately 12 mV below the resting potential of the presynaptic photoreceptors. 4. During the postsynaptic noise reduction, the saturated and subsaturated first-order visual interneuron responses were increased up to 9 mV with a time constant of recovery of approximately 10 s. This increase was shown to be caused by the negative shift of the reversal potential of the transmitter-gated (mainly Cl-) conductance, caused apparently by the reduced transmitter input. 5. The results strongly suggest that the photoreceptor transmitter release in fly is tonic, even in dark, and further support the modulation of the synaptic voltage transfer by postsynaptic Cl- extrusion.