Person:

Harvey, Christopher

We studied how the posterior parietal cortex combined new information with ongoing activity dynamics as mice accumulated evidence during a virtual-navigation task. Using new methods to analyze population activity on single trials, we found that activity transitioned rapidly between different sets of active neurons. Each event in a trial — whether an evidence cue or a behavioral choice — caused seconds-long modifications to the probabilities that govern how one activity pattern transitions to the next, forming a short-term memory. A sequence of evidence cues triggered a chain of these modifications resulting in a signal for accumulated evidence. Multiple distinguishable activity patterns were possible for the same accumulated evidence because representations of ongoing events were influenced by previous within and across trial events. Therefore, evidence accumulation need not require the explicit competition between groups of neurons, as in winner-take-all models, but could instead emerge implicitly from general dynamical properties that instantiate short-term memory.

The cortex represents information across widely varying timescales1–5. For instance, sensory cortex encodes stimuli that fluctuate over few tens of milliseconds6,7, whereas in association cortex behavioral choices can require the maintenance of information over seconds8,9. However, it remains poorly understood if diverse timescales result mostly from features intrinsic to individual neurons or from neuronal population activity. This question is unanswered because the timescales of coding in populations of neurons have not been studied extensively, and population codes have not been compared systematically across cortical regions. Here we discovered that population codes can be essential to achieve long coding timescales. Furthermore, we found that the properties of population codes differ between sensory and association cortices. We compared coding for sensory stimuli and behavioral choices in auditory cortex (AC) and posterior parietal cortex (PPC) as mice performed a sound localization task. Auditory stimulus information was stronger in AC than in PPC, and both regions contained choice information. Although AC and PPC coded information by tiling in time neurons that were transiently informative for ~200 milliseconds, the areas had major differences in functional coupling between neurons, measured as activity correlations that could not be explained by task events. Coupling among PPC neurons was strong and extended over long time lags, whereas coupling among AC neurons was weak and short-lived. Stronger coupling in PPC led to a population code with long timescales and a representation of choice that remained consistent for approximately one second. In contrast, AC had a code with rapid fluctuations in stimulus and choice information over hundreds of milliseconds. Our results reveal that population codes differ across cortex and that coupling is a variable property of cortical populations that affects the timescale of information coding and the accuracy of behavior.

SUMMARY Optical methods of interrogating neural circuits have emerged as powerful tools for understanding how the brain drives behaviors. Optogenetic proteins are widely used to control neuronal activity, while genetically encoded fluorescent reporters are used to monitor activity. These proteins are often expressed by injecting viruses, which frequently leads to inconsistent experiments due to misalignment of expression and optical components. Here, we describe how silk fibroin films simplify optogenetic experiments by providing targeted delivery of viruses. Films composed of silk fibroin and virus are applied to the surface of implantable optical components. After surgery, silk releases the virus to transduce nearby cells and provide localized expression around optical fibers and endoscopes. Silk films can also be used to express genetically encoded sensors in large cortical regions by using cranial windows coated with a silk/virus mixture. The ease of use and improved performance provided by silk make this a promising approach for optogenetic studies.