150 Psychologie
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Developmental loss of ErbB4 in PV interneurons disrupts state-dependent cortical circuit dynamics
(2020)
GABAergic inhibition plays an important role in the establishment and maintenance of cortical circuits during development. Neuregulin 1 (Nrg1) and its interneuron-specific receptor ErbB4 are key elements of a signaling pathway critical for the maturation and proper synaptic connectivity of interneurons. Using conditional deletions of the ERBB4 gene in mice, we tested the role of this signaling pathway at two developmental timepoints in parvalbumin-expressing (PV) interneurons, the largest subpopulation of cortical GABAergic cells. Loss of ErbB4 in PV interneurons during embryonic, but not late postnatal, development leads to alterations in the activity of excitatory and inhibitory cortical neurons, along with severe disruption of cortical temporal organization. These impairments emerge by the end of the second postnatal week, prior to the complete maturation of the PV interneurons themselves. Early loss of ErbB4 in PV interneurons also results in profound dysregulation of excitatory pyramidal neuron dendritic architecture and a redistribution of spine density at the apical dendritic tuft. In association with these deficits, excitatory cortical neurons exhibit normal tuning for sensory inputs, but a loss of state-dependent modulation of the gain of sensory responses. Together these data support a key role for early developmental Nrg1/ErbB4 signaling in PV interneurons as powerful mechanism underlying the maturation of both the inhibitory and excitatory components of cortical circuits.
Excess neuronal branching allows for innervation of specific dendritic compartments in cortex
(2019)
The connectivity of cortical microcircuits is a major determinant of brain function; defining how activity propagates between different cell types is key to scaling our understanding of individual neuronal behaviour to encompass functional networks. Furthermore, the integration of synaptic currents within a dendrite depends on the spatial organisation of inputs, both excitatory and inhibitory. We identify a simple equation to estimate the number of potential anatomical contacts between neurons; finding a linear increase in potential connectivity with cable length and maximum spine length, and a decrease with overlapping volume. This enables us to predict the mean number of candidate synapses for reconstructed cells, including those realistically arranged. We identify an excess of putative connections in cortical data, with densities of neurite higher than is necessary to reliably ensure the possible implementation of any given connection. We show that potential contacts allow the particular implementation of connectivity at a subcellular level.
Spike count correlations (SCCs) are ubiquitous in sensory cortices, are characterized by rich structure and arise from structured internal interactions. Yet, most theories of visual perception focus exclusively on the mean responses of individual neurons. Here, we argue that feedback interactions in primary visual cortex (V1) establish the context in which individual neurons process complex stimuli and that changes in visual context give rise to stimulus-dependent SCCs. Measuring V1 population responses to natural scenes in behaving macaques, we show that the fine structure of SCCs is stimulus-specific and variations in response correlations across-stimuli are independent of variations in response means. Moreover, we demonstrate that stimulus-specificity of SCCs in V1 can be directly manipulated by controlling the high-order structure of synthetic stimuli. We propose that stimulus-specificity of SCCs is a natural consequence of hierarchical inference where inferences on the presence of high-level image features modulate inferences on the presence of low-level features.
Reducing neuronal size results in less cell membrane and therefore lower input conductance. Smaller neurons are thus more excitable as seen in their voltage responses to current injections in the soma. However, the impact of a neuron’s size and shape on its voltage responses to synaptic activation in dendrites is much less understood. Here we use analytical cable theory to predict voltage responses to distributed synaptic inputs and show that these are entirely independent of dendritic length. For a given synaptic density, a neuron’s response depends only on the average dendritic diameter and its intrinsic conductivity. These results remain true for the entire range of possible dendritic morphologies irrespective of any particular arborisation complexity. Also, spiking models result in morphology invariant numbers of action potentials that encode the percentage of active synapses. Interestingly, in contrast to spike rate, spike times do depend on dendrite morphology. In summary, a neuron’s excitability in response to synaptic inputs is not affected by total dendrite length. It rather provides a homeostatic input-output relation that specialised synapse distributions, local non-linearities in the dendrites and synaptic plasticity can modulate. Our work reveals a new fundamental principle of dendritic constancy that has consequences for the overall computation in neural circuits.
Human language relies on hierarchically structured syntax to facilitate efficient and robust communication. The correct processing of syntactic information is essential for successful communication between speakers. As an abstract level of language, syntax has often been studied separately from the physical form of the speech signal, thus often masking the interactions that can promote better syntactic processing in the human brain. We analyzed a MEG dataset to investigate how acoustic cues, specifically prosody, interact with syntactic operations. We examined whether prosody enhances the cortical encoding of syntactic representations. We decoded left-sided dependencies directly from brain activity and evaluated possible modulations of the decoding by the presence of prosodic boundaries. Our findings demonstrate that prosodic boundary presence improves the representation of left-sided dependencies, indicating the facilitative role of prosodic cues in processing abstract linguistic features. This study gives neurobiological evidence for the boosting of syntactic processing via interaction with prosody.
Inter-areal coherence has been hypothesized as a mechanism for inter-areal communication. Indeed, empirical studies have observed an increase in inter-areal coherence with attention. Yet, the mechanisms underlying changes in coherence remain largely unknown. Both attention and stimulus salience are associated with shifts in the peak frequency of gamma oscillations in V1, which suggests that the frequency of oscillations may play a role in facilitating changes in inter-areal communication and coherence. In this study, we used computational modeling to investigate how the peak frequency of a sender influences inter-areal coherence. We show that changes in the magnitude of coherence are largely determined by the peak frequency of the sender. However, the pattern of coherence depends on the intrinsic properties of the receiver, specifically whether the receiver integrates or resonates with its synaptic inputs. Because resonant receivers are frequency-selective, resonance has been proposed as a mechanism for selective communication. However, the pattern of coherence changes produced by a resonant receiver is inconsistent with empirical studies. By contrast, an integrator receiver does produce the pattern of coherence with frequency shifts in the sender observed in empirical studies. These results indicate that coherence can be a misleading measure of inter-areal interactions. This led us to develop a new measure of inter-areal interactions, which we refer to as Explained Power. We show that Explained Power maps directly to the signal transmitted by the sender filtered by the receiver, and thus provides a method to quantify the true signals transmitted between the sender and receiver. Together, these findings provide a model of changes in inter-areal coherence and Granger-causality as a result of frequency shifts.
The pitfalls of measuring representational similarity using representational similarity analysis
(2022)
A core challenge in neuroscience is to assess whether diverse systems represent the world similarly. Representational Similarity Analysis (RSA) is an innovative approach to address this problem and has become increasingly popular across disciplines from machine learning to computational neuroscience. Despite these successes, RSA regularly uncovers difficult-to-reconcile and contradictory findings. Here we demonstrate the pitfalls of using RSA to infer representational similarity and explain how contradictory findings arise and support false inferences when left unchecked. By comparing neural representations in primate, human and computational models, we reveal two problematic phenomena that are ubiquitous in current research: a “mimic” effect, where confounds in stimuli can lead to high RSA scores between provably dissimilar systems, and a “modulation effect”, where RSA-scores become dependent on stimuli used for testing. Since our results bear on existing findings and inferences, we provide recommendations to avoid these pitfalls and sketch a way forward.
The pitfalls of measuring representational similarity using representational similarity analysis
(2022)
A core challenge in cognitive and brain sciences is to assess whether different biological systems represent the world in a similar manner. Representational Similarity Analysis (RSA) is an innovative approach to address this problem and has become increasingly popular across disciplines ranging from artificial intelligence to computational neuroscience. Despite these successes, RSA regularly uncovers difficult-to-reconcile and contradictory findings. Here, we demonstrate the pitfalls of using RSA and explain how contradictory findings arise due to false inferences about representational similarity based on RSA-scores. In a series of studies that capture increasingly plausible training and testing scenarios, we compare neural representations in computational models, primate cortex and human cortex. These studies reveal two problematic phenomena that are ubiquitous in current research: a “mimic” effect, where confounds in stimuli can lead to high RSA-scores between provably dissimilar systems, and a “modulation effect”, where RSA-scores become dependent on stimuli used for testing. Since our results bear on a number of influential findings and the inferences drawn by current practitioners in a wide range of disciplines, we provide recommendations to avoid these pitfalls and sketch a way forward to a more solid science of representation in cognitive systems.
Representational Similarity Analysis (RSA) is an innovative approach used to compare neural representations across individuals, species and computational models. Despite its popularity within neuroscience, psychology and artificial intelligence, this approach has led to difficult-to-reconcile and contradictory findings, particularly when comparing primate visual representations with deep neural networks (DNNs). Here, we demonstrate how such contradictory findings could arise due to incorrect inferences about mechanism when comparing complex systems processing high-dimensional stimuli. In a series of studies comparing computational models, primate cortex and human cortex we find two problematic phenomena: a “mimic effect”, where confounds in stimuli can lead to high RSA-scores between provably dissimilar systems, and a “modulation effect”, where RSA- scores become dependent on stimuli used for testing. Since our results bear on a number of influential findings, we provide recommendations to avoid these pitfalls and sketch a way forward to a more solid science of representation in cognitive systems.
Some pitfalls of measuring representational similarity using Representational Similarity Analysis
(2022)
A core challenge in cognitive and brain sciences is to assess whether different biological systems represent the world in a similar manner. Representational Similarity Analysis (RSA) is an innovative approach that addresses this problem by looking for a second-order isomorphisim in neural activation patterns. This innovation makes it easy to compare latent representations across individuals, species and computational models, and accounts for its popularity across disciplines ranging from artificial intelligence to computational neuroscience. Despite these successes, using RSA has led to difficult-to-reconcile and contradictory findings, particularly when comparing primate visual representations with deep neural networks (DNNs): even though DNNs have been shown to learn and behave in vastly different ways to humans, comparisons based on RSA have shown striking similarities in some studies. Here, we demonstrate some pitfalls of using RSA and explain how contradictory findings can arise due to false inferences about representational similarity based on RSA-scores. In a series of studies that capture increasingly plausible training and testing scenarios, we compare neural representations in computational models, primate cortex and human cortex. These studies reveal two problematic phenomena that are ubiquitous in current research: a “mimic effect”, where confounds in stimuli can lead to high RSA-scores between provably dissimilar systems, and a “modulation effect”, where RSA-scores become dependent on stimuli used for testing. Since our results bear on a number of influential findings, such as comparisons made between human visual representations and those of primates and DNNs, we provide recommendations to avoid these pitfalls and sketch a way forward to a more solid science of representation in cognitive systems.