Blanc SVSE 4 - Blanc - SVSE 4 - Neurosciences

How the balance of excitation and inhibition shapes orientation selectivity and center-surround interactions in superficial layers in area V1: a combined experimental and modeling project – BalaV1

Can the compensation between excitation and inhibition account for the selectivity of neurons in the primary visual cortex?

The activity of neurons in the primary visual cortex (V1) displays a very high level of synaptic «noise«. But is it really «noise«? Theoretical studies indicated that the «noise« is the result of the strong interactions - excitatory and inhibitory – taking place between neurons. These interactions must be balanced (so-called «balanced« state) for maintaining the activity level in a reasonable range. Our aim is to study the role of this emerging noise in the genesis of the responses in area V1.

«Balanced« recurrent networks and specificity of neuronal responses

Our goal is to determine how fluctuations in the membrane potential (or synaptic noise) affect the different field properties of neurons in area V1, in particular orientation selectivity and center-surround interactions. The mechanisms underlying orientation selectivity, for example, have been hotly debated over the past 50 years. The theories that claim to explain orientation selectivity are however all assuming that the involved network has a functional organization, i.e., that neurons displaying similar receptive field properties tend to be more interconnected than neurons with different receptive field properties. However, the recent theoretical work of D. Hansel and C. van Vreeswijk suggests that such architecture is not necessary for the emergence of the orientation selectivity: this selectivity may be present even if connections between neurons are not specific or only weakly so. The only necessary condition is that the network operates in a «balanced« regime, which is a generic feature of the dynamics of strongly recurrent neural networks. A feature of the balanced condition is the presence of strong temporal fluctuations in the activity of the neurons, particularly in the membrane potential. Our goal is to characterize – by combining theory and experiments - the properties of these fluctuations and their dependencies of the degree of specificity of the connections, and to examine their functional roles in primates (monkeys, marmosets). In a first step we will foce on orientation selectivity. In a second step we will examine whether this approach can be generalized to other dimensions of stimuli (contrast and size).

Our project is based on a synergy between theoretical and experimental approaches imbricating each other. Experimentally we use a mesoscopic approach - intrinsic optical imaging - which allows us to visualize the organization of orientation selectivity and to produce maps that will guide other approaches. Extracellular single unit recording using multi-site laminar probes and recording of calcium signals using two-photon imaging method allow access to the activity of individual neurons. Intracellular recording allows visualizing fluctuations in the membrane potential, while field potential recording allows characterizing the fluctuations at the level of a population of neurons. Our experimental approach also uses two animal models: macaque monkey and marmoset monkeys. Our visual stimuli were initially adapted to the study of the responses as a function of the orientation, contrast and size of the activated visual field. More recently we used a new family of stimuli that allow, according to the theory, different activations depending on whether the neurons are located in orientation domains where neighboring neurons have the same orientation or whether the neurons are located in pinwheels where all orientations are spatially coalescent. These stimuli are based on a precise definition of the distribution in a Fourier space in 3D (Fx, Fy, Ft) that can give a family of stimuli in x, y, t space. The theoretical approach is based on parallelized code on GPUs to simulate layer 2/3 of the primary visual cortex, with or without orientation maps. The simulated network consists of a network comprising two populations of neurons (excitatory and inhibitory) modeled with Hodgkin-Huxley formalism (only one compartment - the soma - with sodium and potassium currents) interacting via excitatory (AMPA, NMDA ) and inhibitory (GABA receptor) conductances. This network models the effects of the input of layer 4 neurons - supposedly orientation selective - on layer 2/3 cells.

Two Cynomolgus Monkeys (Macaca fascicularis) have been used in semi-chronic experiments. In a first step, maps of orientation selectivity were generated. Then we performed electrophysiological recordings using multi-contact laminar probes that targeted either orientation domains or pinwheels. We used for the first time the multi-oriented stimuli mentioned above. The acquired data is being analyzed. We also have data to examine interactions between the contrast and the size of the stimuli with single-unit responses recorded simultaneously with local field potentials.
The theoretical study shows that an excess of bidirectional connections does not affect the orientation selectivity properties in the neurons but that it affects the timescales on which the activity - and consequently field potentials - fluctuate. To examine the behavior of a network with an orientation map (corresponds to the primary visual cortex of monkeys, for example), we implemented our model in a well-defined map in layer 4. Connections from layer 4 to layer 2/3 as well as recurrent interactions layer 2/3 depend solely on distance. Our simulations indicate that the map emerging in layer 2/3 is «fuzzy« if the selectivity properties are ordered on spatial scales of the order of 150 microns, they are very heterogeneous in smaller scale.

Following a meeting in March 2015, we agreed on the use of a common stimulation paradigm. The stimuli correspond to textures containing orientations whose distribution varies in a parameterized way. The project's theoretical studies predict that the response of neurons to these stimuli will be different depending on the neuron location in the orientation map (pinwheels vs. domain) and on their positions in the cortical layers (layer 4 vs. Layer 2/3). This paradigm is an emerging decision of our collaboration and has the fundamental benefit of unifying our work around a single parametric exploration. We hope to be able to compare, in the months to come, our theoretical results with experimental data obtained in the monkey.

Four referenced publications in refereed journals and eight communications in international conferences.

In carnivores and primates the orientation selectivity (OS) of the cells in the primary visual cortex (V1) is organized in maps in which preferred orientations (POs) of the cells change gradually except near “pinwheels”, around which all orientations are present. Over the last half-century the mechanism for OS has been hotly debated. However the theories that purport to explain OS have almost all considered cortical networks in which the neurons receive input preferentially from cells with similar PO. Such theories certainly capture the connectivity for neurons in orientation domains where neurons are surrounded by other cells with similar PO. However this does not necessarily hold near pinwheels: because of the discontinuous change in orientation preference at the pinwheel, neurons in this area are surrounded by cells of all preferred orientations. Thus if the probability of connection is solely dependent on anatomical distance, the inputs that these neurons receive should represent all orientations by roughly the same amount. Thus one may expect that the response of the cells near pinwheels should hardly vary with orientation, in contrast to experimental data. As a result, the common belief is that, at least near pinwheels, the connectivity depends also on the differences between preferred orientation.
The situation near pinwheels in V1 of carnivores and primates is similar to that in the whole of V1 of rodents. In these species, neurons in V1 are OS but the network does not exhibit an orientation map and the surround of the cells represents all orientations roughly equally. In a recent theoretical paper (Hansel and van Vreeswijk 2012) we have demonstrated that in this situation, the response of the cells can still be orientation selective provided that the network operates in the balanced regime.
Here we hypothesize that V1 with an orientation map operates in the balanced regime and therefore neurons can exhibit OS near pinwheels even in the absence of functional specific connectivity. The goal of this interdisciplinary project is to investigate whether the “balance hypothesis” holds for layer 2/3 in V1 of primate and carnivore and whether the functional organization observed in that layer can be accounted for without feature specific connectivity. We will combine modeling and experiments to investigate how the response of the neurons – the mean firing, the mean voltage, the inhibitory and excitatory conductances and importantly, the power spectrum of their fluctuations – vary with the location in the map, and also how a population of neurons – LFP, voltage-sensitive dye imaging or 2 photons – is affected by the various parameters used to test the system. Whether V1 indeed operates in the balanced regime in more realistic conditions will be further investigated by determining how the local network responds to visual stimuli beyond the classical receptive field. We will investigate this issue in models of layer 2/3 representing multiple hypercolumns to characterize center-surround interactions and their dependence on the long-range connectivity. This will provide us with predictions for center-surround interactions for cells near pinwheels and in orientation domains. These predictions will be tested experimentally.
The proposed project is new and ambitious. It aims at building a comprehensive and coherent understanding of the physiology of V1 layer 2/3 on several spatial scales from single cells to several hypercolumns and to account for this in mechanistic models. To accomplish these ambitious aims, we propose a combination of experimental and computational studies that take advantage of the unique strengths and the complementarity of expertise of 3 research teams. The Paris team has extensive experience in large-scale modeling of V1. The Toulouse and Marseille teams master both intra- and extracellular electrophysiology. In addition, the Marseille team is expert in microscopic and mesoscopic imaging techniques in V1.

Project coordinator

Monsieur Lionel NOWAK (Laboratoire Cerveau et Cognition)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CerCo Laboratoire Cerveau et Cognition
CNRS DR12 _ INT Centre National de la Recherche Scientifique Délégation Provence et Corse _ Institut de Neurosciences de la Timone
LNP Laboratory of Neurophysics and Physiology

Help of the ANR 511,160 euros
Beginning and duration of the scientific project: October 2013 - 48 Months

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