Dalgleish, H. W. P. | Search bioRxiv

bioRxiv2024

A latent pool of neurons silenced by sensory-evoked inhibition can be recruited to enhance perception

Which patterns of neural activity in sensory cortex are relevant for perceptual decision-making? To address this question, we used simultaneous two-photon calcium imaging and targeted two-photon optogenetics to probe barrel cortex activity during a perceptual discrimination task. Head-fixed mice discriminated bilateral whisker deflections and reported decisions by licking left or right. Two-photon calcium imaging revealed sparse coding of contralateral and ipsilateral whisker input in layer 2/3 while most neurons did not show task-related activity. Activating small groups of pyramidal neurons using two-photon holographic photostimulation evoked a perceptual bias that scaled with the number of neurons photostimulated. This effect was dominated by the optogenetic activation of a small number of non-coding neurons, which did not show sensory or motor-related activity during task performance. Patterned photostimulation also revealed potent recruitment of cortical inhibition during sensory processing, which strongly and preferentially suppressed non-coding neurons. Our results provide a novel perspective on the circuit basis for the sparse coding model of somatosensory processing in which a pool of non-coding neurons, selectively suppressed by strong network inhibition during whisker stimulation, can be recruited to enhance perception. HighlightsO_LIAll-optical interrogation of barrel cortex during bilateral whisker discrimination C_LIO_LISparse coding of contralateral and ipsilateral whisker information C_LIO_LISelective sensory-evoked inhibition helps ensure sparse coding C_LIO_LIOptogenetic recruitment of stimulus non-coding neurons can aid perception C_LI

neuroscience↗

bioRxiv2021

All-optical interrogation of neural circuits in behaving mice

Recent advances combining two-photon calcium imaging and two-photon optogenetics with digital holography now allow us to read and write neural activity in vivo at cellular resolution with millisecond temporal precision. Such "all-optical" techniques enable experimenters to probe the impact of functionally defined neurons on neural circuit function and behavioural output with new levels of precision. This protocol describes the experimental strategy and workflow for successful completion of typical all-optical interrogation experiments in awake, behaving head-fixed mice. We describe modular procedures for the setup and calibration of an all-optical system, the preparation of an indicator and opsin-expressing and task-performing animal, the characterization of functional and photostimulation responses and the design and implementation of an all-optical experiment. We discuss optimizations for efficiently selecting and targeting neuronal ensembles for photostimulation sequences, as well as generating photostimulation response maps from the imaging data that can be used to examine the impact of photostimulation on the local circuit. We demonstrate the utility of this strategy using all-optical experiments in three different brain areas - barrel cortex, visual cortex and hippocampus - using different experimental setups. This approach can in principle be adapted to any brain area for all-optical interrogation experiments to probe functional connectivity in neural circuits and for investigating the relationship between neural circuit activity and behaviour.

neuroscience↗