Completed Psychology & Behaviour Brain & Nervous System

All-optical interrogation of neural circuits during behaviour

Funder Wellcome Charity-funded
Recipient organisation University of Oxford
Funding £1.3M
Period Sept 2017 — May 2023

In plain English

AI plain-English summary

Mice will have their brain activity read and rewritten in real time as they make decisions with their whiskers, using a laser-based system that both records and controls individual neurons simultaneously. This matters because neuroscientists have long been able to watch brain cells fire or artificially trigger them, but rarely both at once in the same animal during behaviour. The gap is a fundamental one: we do not know how many neurons, firing in what pattern, are actually necessary for a mouse to feel a touch and act on it. Without that knowledge, theories of how the brain encodes perception remain untestable. If this succeeds, the researcher can answer a concrete question—what is the minimum spatiotemporal pattern of neural activity that creates a percept? That is a direct test of the neural code itself. This is fundamental science with no immediate clinical or engineering application. But similar work on the sensory cortex has, in the past, informed brain-computer interfaces and closed-loop prosthetics. A precise understanding of how neural ensembles encode decisions could eventually guide devices that restore sensation or movement in people with spinal cord injury or limb loss.

View original technical description
Neural circuits display complex spatiotemporal patterns of activity on the millisecond timescale. Understanding how these activity patterns drive behaviour is a fundamental problem in neuroscience. To address this challenge, I have recently introduced a novel approach that combines simultaneous two-photon calcium imaging and two-photon targeted optogenetic photostimulation with the use of a spatial light modulator (SLM) to provide 'all-optical' readout and manipulation of the same neurons in vivo. I propose to probe the neural code in mouse barrel cortex during sensory-guided behavioural tasks by using this approach to uncover the underlying mechanisms of decoding and encoding of information by ensembles of neurons. I will train mice to make perceptual decisions based on quantitative control of cortical activity, as well as perturb neural activity in somatosensory cortex while animals are performing discrimination tasks using their whiskers. I can perform decisive tests of theoretical models describing the neural code by assessing the spatiotemporal pattern of activation required in somatosensory cortex to drive a behavioral response. These experiments will shed light on how many neurons with which functional signature are minimally sufficient to subserve a percept.

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Researchers

Adam Max PACKER (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Probing principles of neural coding with all-optical interrogation in behaving mice
All-optical readout and manipulation of neural circuits in the intact mammalian brain
Neural circuitry underlying non-sensory responses in sensory cortex
Cortical circuits underlying visual decision-making behaviors in mice
From single neuron perturbation in vivo to behaviour.

Original classification

Sir Henry Dale Fellowship

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