Structural to functional synaptic conversion

Computer-implemented methods, software, and systems for determining functional synapses from given structural touches between cells in a neuronal circuit are described. One computer-implemented method for determining functional synapses from predetermined synapses of connections between two cells in a neuronal circuit, includes determining, from the predetermined synapses, the functional synapses by leaving a portion of the connections unused, e.g. for activation by plasticity mechanisms.

Adaptation of short-term plasticity parameters via error-driven learning may explain the correlation between activity-dependent synaptic properties, connectivity motifs and target specificity

Michele Giugliano, Eleni Vasilaki

The anatomical connectivity among neurons has been experimentally found to be largely non-random across brain areas. This means that certain connectivity motifs occur at a higher frequency than would be expected by chance. Of particular interest, short-term synaptic plasticity properties were found to colocalize with specific motifs: an over-expression of bidirectional motifs has been found in neuronal pairs where short-term facilitation dominates synaptic transmission among the neurons, whereas an over-expression of unidirectional motifs has been observed in neuronal pairs where short-term depression dominates. In previous work we found that, given a network with fixed short-term properties, the interaction between short- and long-term plasticity of synaptic transmission is sufficient for the emergence of specific motifs. Here, we introduce an error-driven learning mechanism for short-term plasticity that may explain how such observed correspondences develop from randomly initialized dynamic synapses. By allowing synapses to change their properties, neurons are able to adapt their own activity depending on an error signal. This results in more rich dynamics and also, provided that the learning mechanism is target-specific, leads to specialized groups of synapses projecting onto functionally different targets, qualitatively replicating the experimental results of Wang and collaborators.

Frontiers Research Foundation2015

Imaging of AMPA-type glutamate receptors in hippocampal neurons

Michel Kropf

Synaptic plasticity is the ability of the connections between nerve cells, called synapses, to change in strength. The presence of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (AMPAR) at the synapse controls the strength of excitatory transmission and their number can be modulated. Controlled surface insertion of AMPA-type glutamate receptors and their lateral diffusion into synapses are proposed to be major mechanisms for the regulation of synaptic plasticity. Here we applied the recently established Acyl-Carrier-Protein-labeling technique in combination with lentiviral expression in hippocampal neurons to label individually ACP-tagged AMPA receptor subunits at the surface of neurons. This technique uses a carrier protein from the fatty acid synthesis and a mutant therof as a tag, which were fused by genetic engineering to the AMPAR subunits. The labeling procedure is specific for proteins, AMPARs in our case, which are present at the plasma membrane of the cell. We show that this technique allows to differentially label two subunits of the receptor. Moreover, these subunits are integrated into heteromeric receptors together with endogenous subunits, and these labeled receptors are targeted to functional synapses. The diffusion coefficient of labeled GluR2 at the surface of living neurons is significantly higher in GluR2/GluR3-infected neurons compared to GluR1/GluR2-infected neurons suggesting a higher mobility of GluR2/3 receptors compared to GluR1/2 receptors. Finally, in sequential labeling experiments we detected newly inserted receptor subunits colocalized with presynaptic markers. The GluR1 subunit displayed a faster kinetics of insertion compare to the other subunits. Internalized GluR2 receptors have been shown to accumulate in perinuclear late endosomes in HEK 293T cells. Moreover, we expressed and labeled surface tagged-GluR2 receptors in hippocampal slices, using similar labeling technique as ACP. High-resolution images, sub-difraction limited, of hippocampal neurons stained for GluR2 were acquired with an experimental scanning near-field optical microscopy (SNOM). Together our results strongly indicate that receptor insertion is faster for GluR1 and that insertion occurs at or in close vicinity of synapses in mature hippocampal neuron cultures.

EPFL2007

Structure and function of the olfactory bulb microcircuit

Michele Pignatelli

The aim of this study is to contribute to understand the physiology of the Olfactory System through detailed microcircuit investigation, adopting advanced electrophysiological and anatomical techniques. Multiple patch clamp recordings allow understanding the structural foundations supporting the network architecture, the biophysical rules adopted by the microcircuit connectivity and the fine dynamic of the synaptic transmission. The study focuses on the Olfactory Bulb microcircuit as a first neuronal processor of sensory inputs. The excitatory elements of the Olfactory Bulb microcircuit are anatomically defined by affiliation to the same receptive field: the Glomerulus. A correlated subthreshold activity between microcircuit elements defines the physiological signature of the microcircuit. We experimentally addressed three fundamental issues: origin of the correlated subthreshold activity, connectivity rules and dynamic of the synaptic transmission. In the first study we attribute the origin of correlated subthreshold activity to a class of pacemaker cells responsible for the synchronization of the population onset and acting therefore as a timer of the microcircuit response. In the second study we investigated the connectivity rules supporting the interaction between excitatory cells. The tight apposition between gap junctions and chemical synapses on the excitatory cells dendrites allows gap junctions to propagate postsynaptic potentials toward surrounding compartments. The result of the propagation is represented by an enhancement in the amplification of the sensory information and an increase in the speed of the reaction time. In the third study we extensively analyzed the mechanisms of the synaptic transmission and the activity dependent properties of synapses, revealing a potential role for the short-term plasticity in the development of the sensory processing. The results of our investigation are going to constitute the foundation of a database available for high definition multi-compartmental modeling of the Olfactory Bulb network.