Nathaniel Caleb Wright

Adaptation towards scale-free dynamics improves cortical stimulus discrimination at the cost of reduced detection

Fundamental to the function of nervous systems is the ability to reorganize to cope with changing sensory input. Although well-studied in single neurons, how such adaptive versatility manifests in the collective population dynamics and function of cerebral cortex remains unknown. Here we measured population neural activity with microelectrode arrays in turtle visual cortex while visually stimulating the retina. First, we found that, following the onset of stimulation, adaptation tunes the collective population dynamics towards a special regime with scale-free spatiotemporal activity, after an initial large-scale transient response. Concurrently, we observed an adaptive tradeoff between two important aspects of population coding–sensory detection and discrimination. As adaptation tuned the cortex toward scale-free dynamics, stimulus discrimination was enhanced, while stimulus detection was reduced. Finally, we used a network-level computational model to show that short-term synaptic depression was sufficient to mechanistically explain our experimental results. In the model, scale-free dynamics emerge only when the model operates near a special regime called criticality. Together our model and experimental results suggest unanticipated functional benefits and costs of adaptation near criticality in visual cortex.

Turtle Dorsal Cortex Pyramidal Neurons Comprise Two Distinct Cell Types with Indistinguishable Visual Responses

A detailed inventory of the constituent pieces in cerebral cortex is considered essential to understand the principles underlying cortical signal processing. Specifically, the search for pyramidal neuron subtypes is partly motivated by the hypothesis that a subtype-specific division of labor could create a rich substrate for computation. On the other hand, the extreme integration of individual neurons into the collective cortical circuit promotes the hypothesis that cellular individuality represents a smaller computational role within the context of the larger network. These competing hypotheses raise the important question to what extent the computational function of a neuron is determined by its individual type or by its circuit connections. We created electrophysiological profiles from pyramidal neurons within the sole cellular layer of turtle visual cortex by measuring responses to current injection using whole-cell recordings. A blind clustering algorithm applied to these data revealed the presence of two principle types of pyramidal neurons. Brief diffuse light flashes triggered membrane potential fluctuations in those same cortical neurons. The apparently network driven variability of the visual responses concealed the existence of subtypes. In conclusion, our results support the notion that the importance of diverse intrinsic physiological properties is minimized when neurons are embedded in a synaptic recurrent network.

Inferring presynaptic population spiking from single-trial membrane potential recordings

BACKGROUND The time-varying membrane potential of a cortical neuron contains important information about the network activity. Extracting this information requires separating excitatory and inhibitory synaptic inputs from single-trial membrane potential recordings without averaging across trials. NEW METHOD We propose a method to extract the time course of excitatory and inhibitory synaptic inputs to a neuron from a single-trial membrane potential recording. The method takes advantage of the differences in the time constants and the reversal potentials of the excitatory and inhibitory synaptic currents, which allows the untangling of the two conductance types. RESULTS We evaluate the applicability of the method on a leaky integrate-and-fire model neuron and find high quality of estimation of excitatory synaptic conductance changes and presynaptic population spikes. Application of the method to a real cortical neuron with known synaptic inputs in a brain slice returns high-quality estimation of the time course of the excitatory synaptic conductance. Application of the method to membrane potential recordings from a cortical pyramidal neuron of an intact brain reveals complex network activity. COMPARISON WITH EXISTING METHODS Existing methods are based on repeated trials and thus are limited to estimating the statistical features of synaptic conductance changes, or, when based on single trials, are limited to special cases, have low temporal resolution, or are impractically complicated. CONCLUSIONS We propose and test an efficient method for estimating the full time course of excitatory and inhibitory synaptic conductances from single-trial membrane potential recordings. The method is sufficiently simple to ensure widespread use in neuroscience.

Induced cortical oscillations in turtle cortex are coherent at the mesoscale of population activity, but not at the microscale of the membrane potential of neurons

Bursts of oscillatory neural activity have been hypothesized to be a core mechanism by which remote brain regions can communicate. Such a hypothesis raises the question to what extent oscillations are coherent across spatially distant neural populations. To address this question, we obtained local field potential (LFP) and membrane potential recordings from the visual cortex of turtle in response to visual stimulation of the retina. The time-frequency analysis of these recordings revealed pronounced bursts of oscillatory neural activity and a large trial-to-trial variability in the spectral and temporal properties of the observed oscillations. First, local bursts of oscillations varied from trial to trial in both burst duration and peak frequency. Second, oscillations of a given recording site were not autocoherent; i.e., the phase did not progress linearly in time. Third, LFP oscillations at spatially separate locations within the visual cortex were more phase coherent in the presence of visual stimulation than during ongoing activity. In contrast, the membrane potential oscillations from pairs of simultaneously recorded pyramidal neurons showed smaller phase coherence, which did not change when switching from black screen to visual stimulation. In conclusion, neuronal oscillations at distant locations in visual cortex are coherent at the mesoscale of population activity, but coherence is largely absent at the microscale of the membrane potential of neurons.NEW & NOTEWORTHY Coherent oscillatory neural activity has long been hypothesized as a potential mechanism for communication across locations in the brain. In this study we confirm the existence of coherent oscillations at the mesoscale of integrated cortical population activity. However, at the microscopic level of neurons, we find no evidence for coherence among oscillatory membrane potential fluctuations. These results raise questions about the applicability of the communication through coherence hypothesis to the level of the membrane potential.

The turtle visual system mediates a complex spatiotemporal transformation of visual stimuli into cortical activity

The three-layered visual cortex of turtle is characterized by extensive intracortical axonal projections and receives non-retinotopic axonal projections from lateral geniculate nucleus. What spatiotemporal transformation of visual stimuli into cortical activity arises from such tangle of malleable cortical inputs and intracortical connections? To address this question, we obtained band-pass filtered extracellular recordings of neural activity in turtle dorsal cortex during visual stimulation of the retina. We discovered important spatial and temporal features of stimulus-modulated cortical local field potential (LFP) recordings. Spatial receptive fields span large areas of the visual field, have an intricate internal structure, and lack directional tuning. The receptive field structure varies across recording sites in a distant-dependent manner. Such composite spatial organization of stimulus-modulated cortical activity is accompanied by an equally multifaceted temporal organization. Cortical visual responses are delayed, persistent, and oscillatory. Further, prior cortical activity contributes globally to adaptation in turtle visual cortex. In conclusion, these results demonstrate convoluted spatiotemporal transformations of visual stimuli into stimulus-modulated cortical activity that, at present, largely evade computational frameworks.

Visual Response Properties In The Three Layer Turtle Visual Cortex

Turtle dorsal cortex provides us with unique insights into cortical processing. It is known to share many features with the mammalian hippocampus and olfactory cortex as well as geniculo-cortical areas in stem amniotes from which mammals evolved. To this end, we have used data from extracellular recordings from microelectrode arrays to study spatial and temporal patterns of responses to visual stimuli as seen in both local field potential and action potentials. We discovered surprisingly large receptive fields, responsiveness to a broad range of stimuli, and high correlation between distant neural ensembles across recording array. Moreover, we found significant response variability regarding latency and strength in the presence of adaptation to both ongoing and visually evoked activity.

The coupling of synaptic inputs to local cortical activity differs among neurons and adapts following stimulus onset

Cortical activity contributes significantly to the high variability of sensory responses of interconnected pyramidal neurons, which has crucial implications for sensory coding. Yet, largely because of technical limitations of in vivo intracellular recordings, the coupling of a pyramidal neurons synaptic inputs to the local cortical activity has evaded full understanding. Here we obtained excitatory synaptic conductance ( g) measurements from putative pyramidal neurons and local field potential (LFP) recordings from adjacent cortical circuits during visual processing in the turtle whole brain ex vivo preparation. We found a range of g-LFP coupling across neurons. Importantly, for a given neuron, g-LFP coupling increased at stimulus onset and then relaxed toward intermediate values during continued visual stimulation. A model network with clustered connectivity and synaptic depression reproduced both the diversity and the dynamics of g-LFP coupling. In conclusion, these results establish a rich dependence of single-neuron responses on anatomical, synaptic, and emergent network properties. NEW & NOTEWORTHY Cortical neurons are strongly influenced by the networks in which they are embedded. To understand sensory processing, we must identify the nature of this influence and its underlying mechanisms. Here we investigate synaptic inputs to cortical neurons, and the nearby local field potential, during visual processing. We find a range of neuron-to-network coupling across cortical neurons. This coupling is dynamically modulated during visual processing via biophysical and emergent network properties.

Response variability and population coupling of cortical synaptic inputs are strongly influenced by network properties

The highly variable spiking of a cortical neuron is “coupled” to that of other neurons in the network. This has implications for sensory coding, and appears to represent a fundamental property of cortical sensory processing. To date, most studies of population coupling have focused on recorded spiking activity, an approach that suffers from several confounding issues. Moreover, the contributions of various network properties to population coupling are largely unexplored. To this end, we recorded the membrane potential (V) and the nearby LFP in the visual cortex of the turtle ex vivo wholebrain preparation during ongoing and visually-evoked activity. We used an algorithm to infer the excitatory conductance (g) from V, and calculated the g-LFP coupling. We found that g-LFP coupling was highly variable across neurons, and increased following visual stimulation before relaxing to intermediate values. To investigate the role of the network, we implemented a driven small-world network of leaky integrate-and-fire neurons. This model reproduces the large across-trial response variability and g-LFP coupling dynamic, and suggests crucial roles for anatomical and emergent network properties.

Adaptation modulates correlated response variability in visual cortex

Cortical sensory responses are highly variable across stimulus presentations. This variability can be correlated across neurons (due to some combination of dense intracortical connectivity, cortical activity level, and cortical state), with fundamental implications for population coding. Yet the interpretation of correlated response variability (or “noise correlation”) has remained fraught with difficulty, in part because of the restriction to extracellular neuronal spike recordings. Here, we measured response variability and its correlation at the most microscopic level of electrical neural activity, the membrane potential, by obtaining dual whole-cell recordings from pairs of cortical pyramidal neurons during visual processing. We found that during visual stimulation, correlated variability adapts towards an intermediate level and that this correlation dynamic is mediated by intracortical mechanisms. A model network with external inputs, synaptic depression, and structure reproduced the observed dynamics of correlated variability. These results establish that intracortical adaptation self-organizes cortical circuits towards a balanced regime at which network coordination maintains an intermediate level.