Local circuit amplification of spatial selectivity in the hippocampus

Local circuit architecture facilitates the emergence of feature selectivity in the cerebral cortex1. In the hippocampus, it remains unknown whether local computations supported by specific connectivity motifs2 regulate the spatial receptive fields of pyramidal cells3. Here we developed an in vivo electroporation method for monosynaptic retrograde tracing4 and optogenetics manipulation at single-cell resolution to interrogate the dynamic interaction of place cells with their microcircuitry during navigation. We found a local circuit mechanism in CA1 whereby the spatial tuning of an individual place cell can propagate to a functionally recurrent subnetwork5 to which it belongs. The emergence of place fields in individual neurons led to the development of inverse selectivity in a subset of their presynaptic interneurons, and recruited functionally coupled place cells at that location. Thus, the spatial selectivity of single CA1 neurons is amplified through local circuit plasticity to enable effective multi-neuronal representations that can flexibly scale environmental features locally without degrading the feedforward input structure

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Distribution of orientation selectivity in recurrent networks of spiking neurons with different random topologies.

Neurons in the primary visual cortex are more or less selective for the orientation of a light bar used for stimulation. A broad distribution of individual grades of orientation selectivity has in fact been reported in all species. A possible reason for emergence of broad distributions is the recurrent network within which the stimulus is being processed. Here we compute the distribution of orientation selectivity in randomly connected model networks that are equipped with different spatial patterns of connectivity. We show that, for a wide variety of connectivity patterns, a linear theory based on firing rates accurately approximates the outcome of direct numerical simulations of networks of spiking neurons. Distance dependent connectivity in networks with a more biologically realistic structure does not compromise our linear analysis, as long as the linearized dynamics, and hence the uniform asynchronous irregular activity state, remain stable. We conclude that linear mechanisms of stimulus processing are indeed responsible for the emergence of orientation selectivity and its distribution in recurrent networks with functionally heterogeneous synaptic connectivity

Image_3_Computational assessment of visual coding across mouse brain areas and behavioural states.TIFF

IntroductionOur brain is bombarded by a diverse range of visual stimuli, which are converted into corresponding neuronal responses and processed throughout the visual system. The neural activity patterns that result from these external stimuli vary depending on the object or scene being observed, but they also change as a result of internal or behavioural states. This raises the question of to what extent it is possible to predict the presented visual stimuli from neural activity across behavioural states, and how this varies in different brain regions.MethodsTo address this question, we assessed the computational capacity of decoders to extract visual information in awake behaving mice, by analysing publicly available standardised datasets from the Allen Brain Institute. We evaluated how natural movie frames can be distinguished based on the activity of units recorded in distinct brain regions and under different behavioural states. This analysis revealed the spectrum of visual information present in different brain regions in response to binary and multiclass classification tasks.ResultsVisual cortical areas showed highest classification accuracies, followed by thalamic and midbrain regions, with hippocampal regions showing close to chance accuracy. In addition, we found that behavioural variability led to a decrease in decoding accuracy, whereby large behavioural changes between train and test sessions reduced the classification performance of the decoders. A generalised linear model analysis suggested that this deterioration in classification might be due to an independent modulation of neural activity by stimulus and behaviour. Finally, we reconstructed the natural movie frames from optimal linear classifiers, and observed a strong similarity between reconstructed and actual movie frames. However, the similarity was significantly higher when the decoders were trained and tested on sessions with similar behavioural states.ConclusionOur analysis provides a systematic assessment of visual coding in the mouse brain, and sheds light on the spectrum of visual information present across brain areas and behavioural states.</p

Orientation Selectivity in Inhibition-Dominated Networks of Spiking Neurons: Effect of Single Neuron Properties and Network Dynamics

<div><p>The neuronal mechanisms underlying the emergence of orientation selectivity in the primary visual cortex of mammals are still elusive. In rodents, visual neurons show highly selective responses to oriented stimuli, but neighboring neurons do not necessarily have similar preferences. Instead of a smooth map, one observes a salt-and-pepper organization of orientation selectivity. Modeling studies have recently confirmed that balanced random networks are indeed capable of amplifying weakly tuned inputs and generating highly selective output responses, even in absence of feature-selective recurrent connectivity. Here we seek to elucidate the neuronal mechanisms underlying this phenomenon by resorting to networks of integrate-and-fire neurons, which are amenable to analytic treatment. Specifically, in networks of perfect integrate-and-fire neurons, we observe that highly selective and contrast invariant output responses emerge, very similar to networks of leaky integrate-and-fire neurons. We then demonstrate that a theory based on mean firing rates and the detailed network topology predicts the output responses, and explains the mechanisms underlying the suppression of the common-mode, amplification of modulation, and contrast invariance. Increasing inhibition dominance in our networks makes the rectifying nonlinearity more prominent, which in turn adds some distortions to the otherwise essentially linear prediction. An extension of the linear theory can account for all the distortions, enabling us to compute the exact shape of every individual tuning curve in our networks. We show that this simple form of nonlinearity adds two important properties to orientation selectivity in the network, namely sharpening of tuning curves and extra suppression of the modulation. The theory can be further extended to account for the nonlinearity of the leaky model by replacing the rectifier by the appropriate smooth input-output transfer function. These results are robust and do not depend on the state of network dynamics, and hold equally well for mean-driven and fluctuation-driven regimes of activity.</p></div

Image_2_Computational assessment of visual coding across mouse brain areas and behavioural states.TIFF

IntroductionOur brain is bombarded by a diverse range of visual stimuli, which are converted into corresponding neuronal responses and processed throughout the visual system. The neural activity patterns that result from these external stimuli vary depending on the object or scene being observed, but they also change as a result of internal or behavioural states. This raises the question of to what extent it is possible to predict the presented visual stimuli from neural activity across behavioural states, and how this varies in different brain regions.MethodsTo address this question, we assessed the computational capacity of decoders to extract visual information in awake behaving mice, by analysing publicly available standardised datasets from the Allen Brain Institute. We evaluated how natural movie frames can be distinguished based on the activity of units recorded in distinct brain regions and under different behavioural states. This analysis revealed the spectrum of visual information present in different brain regions in response to binary and multiclass classification tasks.ResultsVisual cortical areas showed highest classification accuracies, followed by thalamic and midbrain regions, with hippocampal regions showing close to chance accuracy. In addition, we found that behavioural variability led to a decrease in decoding accuracy, whereby large behavioural changes between train and test sessions reduced the classification performance of the decoders. A generalised linear model analysis suggested that this deterioration in classification might be due to an independent modulation of neural activity by stimulus and behaviour. Finally, we reconstructed the natural movie frames from optimal linear classifiers, and observed a strong similarity between reconstructed and actual movie frames. However, the similarity was significantly higher when the decoders were trained and tested on sessions with similar behavioural states.ConclusionOur analysis provides a systematic assessment of visual coding in the mouse brain, and sheds light on the spectrum of visual information present across brain areas and behavioural states.</p

Image_4_Computational assessment of visual coding across mouse brain areas and behavioural states.TIF

IntroductionOur brain is bombarded by a diverse range of visual stimuli, which are converted into corresponding neuronal responses and processed throughout the visual system. The neural activity patterns that result from these external stimuli vary depending on the object or scene being observed, but they also change as a result of internal or behavioural states. This raises the question of to what extent it is possible to predict the presented visual stimuli from neural activity across behavioural states, and how this varies in different brain regions.MethodsTo address this question, we assessed the computational capacity of decoders to extract visual information in awake behaving mice, by analysing publicly available standardised datasets from the Allen Brain Institute. We evaluated how natural movie frames can be distinguished based on the activity of units recorded in distinct brain regions and under different behavioural states. This analysis revealed the spectrum of visual information present in different brain regions in response to binary and multiclass classification tasks.ResultsVisual cortical areas showed highest classification accuracies, followed by thalamic and midbrain regions, with hippocampal regions showing close to chance accuracy. In addition, we found that behavioural variability led to a decrease in decoding accuracy, whereby large behavioural changes between train and test sessions reduced the classification performance of the decoders. A generalised linear model analysis suggested that this deterioration in classification might be due to an independent modulation of neural activity by stimulus and behaviour. Finally, we reconstructed the natural movie frames from optimal linear classifiers, and observed a strong similarity between reconstructed and actual movie frames. However, the similarity was significantly higher when the decoders were trained and tested on sessions with similar behavioural states.ConclusionOur analysis provides a systematic assessment of visual coding in the mouse brain, and sheds light on the spectrum of visual information present across brain areas and behavioural states.</p

Image_1_Computational assessment of visual coding across mouse brain areas and behavioural states.TIF

IntroductionOur brain is bombarded by a diverse range of visual stimuli, which are converted into corresponding neuronal responses and processed throughout the visual system. The neural activity patterns that result from these external stimuli vary depending on the object or scene being observed, but they also change as a result of internal or behavioural states. This raises the question of to what extent it is possible to predict the presented visual stimuli from neural activity across behavioural states, and how this varies in different brain regions.MethodsTo address this question, we assessed the computational capacity of decoders to extract visual information in awake behaving mice, by analysing publicly available standardised datasets from the Allen Brain Institute. We evaluated how natural movie frames can be distinguished based on the activity of units recorded in distinct brain regions and under different behavioural states. This analysis revealed the spectrum of visual information present in different brain regions in response to binary and multiclass classification tasks.ResultsVisual cortical areas showed highest classification accuracies, followed by thalamic and midbrain regions, with hippocampal regions showing close to chance accuracy. In addition, we found that behavioural variability led to a decrease in decoding accuracy, whereby large behavioural changes between train and test sessions reduced the classification performance of the decoders. A generalised linear model analysis suggested that this deterioration in classification might be due to an independent modulation of neural activity by stimulus and behaviour. Finally, we reconstructed the natural movie frames from optimal linear classifiers, and observed a strong similarity between reconstructed and actual movie frames. However, the similarity was significantly higher when the decoders were trained and tested on sessions with similar behavioural states.ConclusionOur analysis provides a systematic assessment of visual coding in the mouse brain, and sheds light on the spectrum of visual information present across brain areas and behavioural states.</p

Population responses of the same PIF network with stronger inhibition.

<p>Same format as <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004045#pcbi-1004045-g001" target="_blank">Fig. 1</a>, for a network of PIF neurons with more recurrent inhibition (), but otherwise identical parameters. (<b>A, B, C, D</b>) Same as panels (A, B, C, E) in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004045#pcbi-1004045-g001" target="_blank">Fig. 1</a>, respectively. (<b>E</b>) The analytical prediction of the linear rectified model (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004045#pcbi.1004045.e164" target="_blank">Eq. (9)</a>) is plotted vs. the results from numerical simulations. Distributions of the difference between the actual and the predicted firing rates (rate diff) at this orientation are shown in the inset for all three contrasts, respectively. (<b>F</b>) Firing rate of neurons during the iteration of the linear rectified rate equation <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004045#pcbi.1004045.e164" target="_blank">Eq. 9</a>. The equation is solved here for and for the medium contrast, . The x-axis shows the steps of the iteration ( in total), for neurons sorted according to their input PO. For clarity, only selected neurons are shown. Pseudo color indicates the firing rate of each neuron. In the inset, the evolution of the residual error is plotted. Error is defined here as the root mean square (RMS) of the difference between the actual firing rate vector and the firing rate vector at each step of iteration, i.e. . Here is the firing rate of neuron estimated from numerical simulations of spiking networks, and is the predicted firing rate of the same neuron at the <i>k</i>th step of iteration of the analytical equation.</p