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Browsing Over 304 Presentations
Welcome/introduction to the mini-symposium
Advanced optical methods for all-optical brain circuits manipulation
Abstract BodyAll-optical manipulation of neuronal circuits requires the control of a single or multiple neuron independently in space and time with single-spike precision and single-cell resolution. This is the next challenge to be faced in optogenetics imposing to move from whole-region optogenetics, using wide field visible light illumination, to what we named circuit optogenetics.
Indeed, in past years, joint progresses in complementary fields including opsin engineering, optical microscopy and multiphoton laser source development have provided the neuroscience community with a sophisticated optogenetics toolbox that has opened the door to neuronal circuits manipulation. Precisely, a large number of variants in microbial opsins have been recently engineered, to speed-up their kinetics, improve their conductance, confine their expression and shift their absorption peak. In parallel, advanced wavefront shaping approaches combined with two-photon excitation have been developed to precisely guide light through tissues using either scanning or parallel light shaping combined with temporal focusing. Furthermore, the combination of holographic light multiplexing with ad hoc spatiotemporal shaping approaches have been demonstrated to have the capability to generate patterned illumination at multiple axially distinct planes, thus enabling optical control of multiple targets within a 3D volume. All in all, these progresses have brought optogenetics into a new phase, circuit optogenetics, where we can determine how multiple parts of a circuit work together in an integrated fashion.
Here, I will review these progresses and show few examples of circuits optogenetics performed in different experimental paradigms.
Towards the Optical Cochlear Implant: Optogenetic Stimulation of the Auditory Pathway
When hearing fails, cochlear implants (CIs) provide open speech perception to most of the currently half a million CI users. CIs bypass the defective sensory organ and stimulate the auditory nerve electrically. The major bottleneck of current CIs is the poor coding of spectral information, which results from wide current spread from each electrode contact. As light can be more conveniently confined, optical stimulation of the auditory nerve presents a promising perspective for a fundamental advance of CIs. Moreover, given the improved frequency resolution of optical excitation and its versatility for arbitrary stimulation patterns the approach also bears potential for auditory research. Developing optogenetic stimulation for auditory research and future CIs requires efforts toward design and characterization of appropriate optogenetic actuators, viral gene transfer to the neurons, as well as engineering of multichannel optical CIs. The presentation will summarize the current state of optogenetic stimulation of the auditory pathway and report on recent breakthroughs on achieving high temporal fidelity and frequency resolution and establishing multichannel optical CIs.
Tools for Analyzing and Controlling Brain Circuits
To enable the understanding and repair of complex biological systems such as the brain, we are creating novel optical tools that enable molecular-resolution maps of large scale systems, as well as technologies for observing and controlling high-speed physiological dynamics in such systems.
Noninvasive Optogenetics by Directed Evolution of Channelrhodopsins and AAV Vectors for Systemic Delivery Across the Blood Brain Barrier
Optogenetics: Clinical Translation for Vision Restoration
Widefield imaging of brain-wide calcium activity in behaving animals
Distal brain areas must coordinate their activity in order to execute everyday behaviors, but many neural recording methods are limited to recording from either a small number of local neurons, or proxies of brain activity in global networks. By using widefield imaging to record from large swaths of dorsal cortex in headfixed, behaving animals, researchers can survey cortical areas involved in a variety of cognitive tasks in an unbiased manner. We'll go over the benefits and drawbacks of widefield imaging, discuss practicalities, how to design experiments that make best use of this method, and how to handle resulting datasets.
Real-time readout from large neuronal populations using template-matching based spike sorting
Measuring distributed correlates of visually-guided behavior across the mouse brain
Vision, choice, action and behavioural engagement arise from neuronal activity that may be distributed across brain regions. To delineate the spatial distribution of neurons underlying these processes, we used Neuropixels probes to record from approximately 30,000 neurons in 42 brain regions of mice performing a visual discrimination task. Neurons in nearly all regions responded non-specifically when the mouse initiated an action. By contrast, neurons encoding visual stimuli and upcoming choices occupied restricted regions in the neocortex, basal ganglia and midbrain. Choice signals were rare and emerged with indistinguishable timing across regions. Midbrain neurons were activated before contralateral choices and were suppressed before ipsilateral choices, whereas forebrain neurons could prefer either side. Brain-wide pre-stimulus activity predicted engagement in individual trials and in the overall task, with enhanced subcortical but suppressed neocortical activity during engagement. These results reveal organizing principles for the distribution of neurons encoding behaviourally relevant variables across the mouse brain.
Decision making across the larval zebrafish brain
Chronic large-scale recording with Neuropixels 2.0 probes
Abstract BodyHow dynamic activity in neural circuits gives rise to behaviour is a central area of interest in neuroscience. A key experimental approach for addressing this question involves measuring extracellular activity of neurons in rodent animal models performing behavioural tasks. Recently developed Neuropixel probes have become a key enabling technology for measuring neural activity in large tissue volumes with high spatiotemporal resolution. Here, we report extracellular recordings obtained with the next-generation Neuropixel 2.0 probes. These probes have a smaller base PCB which facilitates their chronic use in mice. Moreover, in addition to the 1-shank design, a 4-shank probe has been fabricated. As in the previous version, 384 channels can be recorded simultaneously. To allow for performing repeated measurements of neural activity day after day, we have developed a fixture for chronic probe implantation. The fixture is composed of a probe mount to which the probe is permanently attached and which is reversibly mounted on a probe base, which is implanted on the animal. At the end of an experiment, probes can be safely recovered for re-implantation in another experimental animal by removing the probe mount from the probe base, which remains on the animals’ skull. We implanted up to two 4-shank probes in the olfactory cortex of mice and recorded singe-unit responses to odorant stimulation over weeks. Taken together, we believe Neuropixel 2.0 probes provide a key tool for enabling routine chronic recordings, overall increasing the resolution and reliability of in vivo electrophysiology experiment.
Lessons learned from a tissue engineered 3D model of the glial scar
The diseases of the central nervous system (CNS) can have devastating consequences and repercussions at the individual, societal and economical level.
The CNS has a poor regenerative capacity with the astrocytic scar tissue that is formed in the aftermath of an insult being blamed for the little functional recovery that is observed. Although its formation is paramount for our survival, the scar tissue is seen as a hostile territory and a physical barrier for regeneration. But while inevitable, the scar is a dynamic structure, about which the physicality has been largely neglected. How do astrocytes respond to the tissue alterations that occur upon an injury? How does matrix rigidity impact their response? How are these changes orchestrated as disease progresses? How do these alterations contribute to the unbalancing of the forces that inhibit remyelination and axonal growth?
To understand when and how the changes in a CNS lesion environment occur and how these condition the progress of the tissue response and ultimately of the disease, requires a systematic approach, as scar formation results from a plethora of events. We proposed the development of a tissue engineered glial scar model to investigate the astrogliosis process. With this “tool box” we expect to unveil molecular mechanisms that rule not only the astrogliosis dynamics, and contribute to the design of new therapeutic strategies, but also contribute to a better understanding of the CNS homeostasis.