Amplification of Trial-to-Trial Response Variability by Neurons in Visual Cortex

The visual cortex responds to repeated presentations of the same stimulus with high variability. Because the firing mechanism is remarkably noiseless, the source of this variability is thought to lie in the membrane potential fluctuations that result from summated synaptic input. Here this hypothesis is tested through measurements of membrane potential during visual stimulation. Surprisingly, trial-to-trial variability of membrane potential is found to be low. The ratio of variance to mean is much lower for membrane potential than for firing rate. The high variability of firing rate is explained by the threshold present in the function that converts inputs into firing rates. Given an input with small, constant noise, this function produces a firing rate with a large variance that grows with the mean. This model is validated on responses recorded both intracellularly and extracellularly. In neurons of visual cortex, thus, a simple deterministic mechanism amplifies the low variability of summated synaptic inputs into the large variability of firing rate. The computational advantages provided by this amplification are not known

An uncorrelated state for the cortex?

The spike trains of nearby neurons in the sensory cortex are typically thought to be correlated due to mutual connections and common input. Multiple studies have measured these correlations and found them to be substantial (in the range of 10-40%). Two recent papers, however, reported that average correlations can be an order of magnitude smaller. Such low correlations could indicate an ‘uncorrelated state’ for the cortex, where cortical neurons act independently even in the face of strong common input

Visuomotor association orthogonalizes visual cortical population codes

The brain should be best able to associate distinct behavioral responses to sensory stimuli if these stimuli evoke population firing patterns that are close to orthogonal. To investigate whether task training orthogonalizes population codes in primary visual cortex (V1), we measured the orientation tuning of 4,000-neuron populations in mouse V1 before and after training on a visuomotor task. The effect of task training on population codes could be captured by a simple mathematical transformation of firing rates, which suppressed responses to motor-associated stimuli, but only in cells responding to them at intermediate levels. This transformation orthogonalized the representations of the task orientations by sparsening the population responses to these stimuli. The strength of response transformation varied from trial to trial, suggesting a dynamic circuit mechanism rather than static synaptic plasticity. These results indicate a simple process by which visuomotor associations orthogonalize population codes as early as in primary visual cortex

Millisecond Coupling of Local Field Potentials to Synaptic Currents in the Awake Visual Cortex

The cortical local field potential (LFP) is a common measure of population activity, but its relationship to synaptic activity in individual neurons is not fully established. This relationship has been typically studied during anesthesia and is obscured by shared slow fluctuations. Here, we used patch-clamp recordings in visual cortex of anesthetized and awake mice to measure intracellular activity; we then applied a simple method to reveal its coupling to the simultaneously recorded LFP. LFP predicted membrane potential as accurately as synaptic currents, indicating a major role for synaptic currents in the relationship between cortical LFP and intracellular activity. During anesthesia, cortical LFP predicted excitation far better than inhibition; during wakefulness, it predicted them equally well, and visual stimulation further enhanced predictions of inhibition. These findings reveal a central role for synaptic currents, and especially inhibition, in the relationship between the subthreshold activity of individual neurons and the cortical LFP during wakefulness

Challenges and opportunities for large-scale electrophysiology with Neuropixels probes

Electrophysiological methods are the gold standard in neuroscience because they reveal the activity of individual neurons at high temporal resolution and in arbitrary brain locations. Microelectrode arrays based on complementary metal-oxide semiconductor (CMOS) technology, such as Neuropixels probes, look set to transform these methods. Neuropixels probes provide ∼1000 recording sites on an extremely narrow shank, with on-board amplification, digitization, and multiplexing. They deliver low-noise recordings from hundreds of neurons, providing a step change in the type of data available to neuroscientists. Here we discuss the opportunities afforded by these probes for large-scale electrophysiology, the challenges associated with data processing and anatomical localization, and avenues for further improvements of the technology

Sensory coding and the causal impact of mouse cortex in a visual decision.

Correlates of sensory stimuli and motor actions are found in multiple cortical areas, but such correlates do not indicate whether these areas are causally relevant to task performance. We trained mice to discriminate visual contrast and report their decision by steering a wheel. Widefield calcium imaging and Neuropixels recordings in cortex revealed stimulus-related activity in visual (VIS) and frontal (MOs) areas, and widespread movement-related activity across the whole dorsal cortex. Optogenetic inactivation biased choices only when targeted at VIS and MOs,proportionally to each site's encoding of the visual stimulus, and at times corresponding to peak stimulus decoding. A neurometric model based on summing and subtracting activity in VIS and MOs successfully described behavioral performance and predicted the effect of optogenetic inactivation. Thus, sensory signals localized in visual and frontal cortex play a causal role in task performance, while widespread dorsal cortical signals correlating with movement reflect processes that do not play a causal role

Task specificity in mouse parietal cortex

Parietal cortex is implicated in a variety of behavioral processes, but it is unknown whether and how its individual neurons participate in multiple tasks. We trained head-fixed mice to perform two visual decision tasks involving a steering wheel or a virtual T-maze and recorded from the same parietal neurons during these two tasks. Neurons that were active during the T-maze task were typically inactive during the steering-wheel task and vice versa. Recording from the same neurons in the same apparatus without task stimuli yielded the same specificity as in the task, suggesting that task specificity depends on physical context. To confirm this, we trained some mice in a third task combining the steering wheel context with the visual environment of the T-maze. This hybrid task engaged the same neurons as those engaged in the steering-wheel task. Thus, participation by neurons in mouse parietal cortex is task specific, and this specificity is determined by physical context