Simultaneous, cortex-wide dynamics of up to 1 million neurons reveal unbounded scaling of dimensionality with neuron number.

The brain's remarkable properties arise from the collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional "latent" signals reflecting neural computations. However, can such low-dimensional representations truly explain the vast range of brain activity, and if not, what is the appropriate resolution and scale of recording to capture them? Imaging neural activity at cellular resolution and near-simultaneously across the mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number in populations up to 1 million neurons. Although half of the neural variance is contained within sixteen dimensions correlated with behavior, our discovered scaling of dimensionality corresponds to an ever-increasing number of neuronal ensembles without immediate behavioral or sensory correlates. The activity patterns underlying these higher dimensions are fine grained and cortex wide, highlighting that large-scale, cellular-resolution recording is required to uncover the full substrates of neuronal computations.

Simultaneous, cortex-wide and cellular-resolution neuronal population dynamics reveal an unbounded scaling of dimensionality with neuron number.

The brain's remarkable properties arise from collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional "latent" signals reflecting neural computations. However, what would be the biological utility of such a redundant and metabolically costly encoding scheme and what is the appropriate resolution and scale of neural recording to understand brain function? Imaging the activity of one million neurons at cellular resolution and near-simultaneously across mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number. While half of the neural variance lies within sixteen behavior-related dimensions, we find this unbounded scaling of dimensionality to correspond to an ever-increasing number of internal variables without immediate behavioral correlates. The activity patterns underlying these higher dimensions are fine-grained and cortex-wide, highlighting that large-scale recording is required to uncover the full neural substrates of internal and potentially cognitive processes.

High-speed, cortex-wide volumetric recording of neuroactivity at cellular resolution using light beads microscopy.

Two-photon microscopy has enabled high-resolution imaging of neuroactivity at depth within scattering brain tissue. However, its various realizations have not overcome the tradeoffs between speed and spatiotemporal sampling that would be necessary to enable mesoscale volumetric recording of neuroactivity at cellular resolution and speed compatible with resolving calcium transients. Here, we introduce light beads microscopy (LBM), a scalable and spatiotemporally optimal acquisition approach limited only by fluorescence lifetime, where a set of axially separated and temporally distinct foci record the entire axial imaging range near-simultaneously, enabling volumetric recording at 1.41 × 108 voxels per second. Using LBM, we demonstrate mesoscopic and volumetric imaging at multiple scales in the mouse cortex, including cellular-resolution recordings within ~3 × 5 × 0.5 mm volumes containing >200,000 neurons at ~5 Hz and recordings of populations of ~1 million neurons within ~5.4 × 6 × 0.5 mm volumes at ~2 Hz, as well as higher speed (9.6 Hz) subcellular-resolution volumetric recordings. LBM provides an opportunity for discovering the neurocomputations underlying cortex-wide encoding and processing of information in the mammalian brain.

Volumetric Ca2+ Imaging in the Mouse Brain Using Hybrid Multiplexed Sculpted Light Microscopy.

Calcium imaging using two-photon scanning microscopy has become an essential tool in neuroscience. However, in its typical implementation, the tradeoffs between fields of view, acquisition speeds, and depth restrictions in scattering brain tissue pose severe limitations. Here, using an integrated systems-wide optimization approach combined with multiple technical innovations, we introduce a new design paradigm for optical microscopy based on maximizing biological information while maintaining the fidelity of obtained neuron signals. Our modular design utilizes hybrid multi-photon acquisition and allows volumetric recording of neuroactivity at single-cell resolution within up to 1 × 1 × 1.22 mm volumes at up to 17 Hz in awake behaving mice. We establish the capabilities and potential of the different configurations of our imaging system at depth and across brain regions by applying it to in vivo recording of up to 12,000 neurons in mouse auditory cortex, posterior parietal cortex, and hippocampus.

Ultra-low loss dispersion control with chirped transmissive fiber gratings.

Dispersion control is a critical functionality required in systems involving ultra-short (∼100 fs) pulses, and we demonstrate the use of chirped long-period fiber gratings for this purpose. The operation principles of this device share many attributes with the more established fiber Bragg grating technology for dispersion compensation, but with the added benefit of record low loss (0.2 dB) and the potential of being free from group-delay ripple distortions. The bandwidth of the transmissive grating device we demonstrate exceeds 12 nm, and it provides +52 fs/nm of dispersion in the 1 µm wavelength range. This corresponds to the capability of compensating the dispersion of ∼100 fs pulses in approximately meter-long single mode fibers.