Rapid compensatory plasticity revealed by dynamic correlated activity in monkeys in vivo.

To produce adaptive behavior, neural networks must balance between plasticity and stability. Computational work has demonstrated that network stability requires plasticity mechanisms to be counterbalanced by rapid compensatory processes. However, such processes have yet to be experimentally observed. Here we demonstrate that repeated optogenetic activation of excitatory neurons in monkey visual cortex (area V1) induces a population-wide dynamic reduction in the strength of neuronal interactions over the timescale of minutes during the awake state, but not during rest. This new form of rapid plasticity was observed only in the correlation structure, with firing rates remaining stable across trials. A computational network model operating in the balanced regime confirmed experimental findings and revealed that inhibitory plasticity is responsible for the decrease in correlated activity in response to repeated light stimulation. These results provide the first experimental evidence for rapid homeostatic plasticity that primarily operates during wakefulness, which stabilizes neuronal interactions during strong network co-activation.

High-order interactions explain the collective behavior of cortical populations in executive but not sensory areas.

One influential view in neuroscience is that pairwise cell interactions explain the firing patterns of large populations. Despite its prevalence, this view originates from studies in the retina and visual cortex of anesthetized animals. Whether pairwise interactions predict the firing patterns of neurons across multiple brain areas in behaving animals remains unknown. Here, we performed multi-area electrical recordings to find that 2nd-order interactions explain a high fraction of entropy of the population response in macaque cortical areas V1 and V4. Surprisingly, despite the brain-state modulation of neuronal responses, the model based on pairwise interactions captured ∼90% of the spiking activity structure during wakefulness and sleep. However, regardless of brain state, pairwise interactions fail to explain experimentally observed entropy in neural populations from the prefrontal cortex. Thus, while simple pairwise interactions explain the collective behavior of visual cortical networks across brain states, explaining the population dynamics in downstream areas involves higher-order interactions.

Heterogeneous side effects of cortical inactivation in behaving animals.

Cortical inactivation represents a key causal manipulation allowing the study of cortical circuits and their impact on behavior. A key assumption in inactivation studies is that the neurons in the target area become silent while the surrounding cortical tissue is only negligibly impacted. However, individual neurons are embedded in complex local circuits composed of excitatory and inhibitory cells with connections extending hundreds of microns. This raises the possibility that silencing one part of the network could induce complex, unpredictable activity changes in neurons outside the targeted inactivation zone. These off-target side effects can potentially complicate interpretations of inactivation manipulations, especially when they are related to changes in behavior. Here, we demonstrate that optogenetic inactivation of glutamatergic neurons in the superficial layers of monkey primary visual cortex (V1) induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified four types of stimulus-evoked neuronal responses within a cortical column, ranging from full suppression to facilitation, and a mixture of both. Mixed responses were most prominent in middle and deep cortical layers. These results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Importantly, consistent behavioral changes induced by optogenetic inactivation were only achieved when cumulative network activity was homogeneously suppressed. Therefore, careful consideration of the full range of network changes outside the inactivated cortical region is required, as heterogeneous side effects can confound interpretation of inactivation experiments.

Pairwise Synchrony and Correlations Depend on the Structure of the Population Code in Visual Cortex.

In visual areas of primates, neurons activate in parallel while the animal is engaged in a behavioral task. In this study, we examine the structure of the population code while the animal performs delayed match-to-sample tasks on complex natural images. The macaque monkeys visualized two consecutive stimuli that were either the same or different, while being recorded with laminar arrays across the cortical depth in cortical areas V1 and V4. We decode correct choice behavior from neural populations of simultaneously recorded units. Utilizing decoding weights, we divide neurons into most informative and less informative and show that most informative neurons in V4, but not in V1, are more strongly synchronized, coupled, and correlated than less informative neurons. Because neurons are divided into two coding pools according to their coding preference, in V4, but not in V1, spiking synchrony, coupling, and correlations within the coding pool are stronger than across coding pools.

An Open Resource for Non-human Primate Optogenetics.

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.

Reading-out task variables as a low-dimensional reconstruction of neural spike trains in single trials.

We propose a new model of the read-out of spike trains that exploits the multivariate structure of responses of neural ensembles. Assuming the point of view of a read-out neuron that receives synaptic inputs from a population of projecting neurons, synaptic inputs are weighted with a heterogeneous set of weights. We propose that synaptic weights reflect the role of each neuron within the population for the computational task that the network has to solve. In our case, the computational task is discrimination of binary classes of stimuli, and weights are such as to maximize the discrimination capacity of the network. We compute synaptic weights as the feature weights of an optimal linear classifier. Once weights have been learned, they weight spike trains and allow to compute the post-synaptic current that modulates the spiking probability of the read-out unit in real time. We apply the model on parallel spike trains from V1 and V4 areas in the behaving monkey macaca mulatta, while the animal is engaged in a visual discrimination task with binary classes of stimuli. The read-out of spike trains with our model allows to discriminate the two classes of stimuli, while population PSTH entirely fails to do so. Splitting neurons in two subpopulations according to the sign of the weight, we show that population signals of the two functional subnetworks are negatively correlated. Disentangling the superficial, the middle and the deep layer of the cortex, we show that in both V1 and V4, superficial layers are the most important in discriminating binary classes of stimuli.

Integration of cortical population signals for visual perception.

Visual stimuli evoke heterogeneous responses across nearby neural populations. These signals must be locally integrated to contribute to perception, but the principles underlying this process are unknown. Here, we exploit the systematic organization of orientation preference in macaque primary visual cortex (V1) and perform causal manipulations to examine the limits of signal integration. Optogenetic stimulation and visual stimuli are used to simultaneously drive two neural populations with overlapping receptive fields. We report that optogenetic stimulation raises firing rates uniformly across conditions, but improves the detection of visual stimuli only when activating cells that are preferentially-tuned to the visual stimulus. Further, we show that changes in correlated variability are exclusively present when the optogenetically and visually-activated populations are functionally-proximal, suggesting that correlation changes represent a hallmark of signal integration. Our results demonstrate that information from functionally-proximal neurons is pooled for perception, but functionally-distal signals remain independent.

High-order coordination of cortical spiking activity modulates perceptual accuracy.

The accurate relay of electrical signals within cortical networks is key to perception and cognitive function. Theoretically, it has long been proposed that temporal coordination of neuronal spiking activity controls signal transmission and behavior. However, whether and how temporally precise neuronal coordination in population activity influences perception are unknown. Here, we recorded populations of neurons in early and mid-level visual cortex (areas V1 and V4) simultaneously to discover that the precise temporal coordination between the spiking activity of three or more cells carries information about visual perception in the absence of firing rate modulation. The accuracy of perceptual responses correlated with high-order spiking coordination within V4, but not V1, and with feedforward coordination between V1 and V4. These results indicate that while visual stimuli are encoded in the discharge rates of neurons, perceptual accuracy is related to temporally precise spiking coordination within and between cortical networks.