ESI Systems Neuroscience Conference 2020
Causal Approaches in Neuroscience
The Ernst Strüngmann Institute Systems Neuroscience Conference (ESI SyNC) 2020 will be held this year on August 24th-26th as a fully virtual conference.
This year’s theme is Causal Approaches in Neuroscience.
The conference will feature ten internationally renowned speakers who will give talks on optogenetic approaches, microstimulation, cortical cooling and other forms of neuronal activity manipulation. Ample time for both formal and informal discussion has been included in the schedule. There will also be an online poster session for which we welcome submissions. As part of the schedule, a method-focused session on Viral Approaches in Monkeys will be held.
Systems Neuroscience Section, Primate Research Institute, Kyoto University Research works using nonhuman primates (NHPs) play vital roles in the progress in medical and life sciences, because they are the evolutionarily closest to humans among the animal species used for invasive experiments, and because they resemble humans in terms of body structure and function. Since macaque monkeys have the excellent ability to learn and perform various motor and cognitive tasks, they are thought to be useful not only for elucidating higher brain functions, but also for revealing the pathophysiology of psychiatric and neurological disorders and establishing innovative therapeutic approaches for these disorders. Therefore, considerable lines of anatomical and physiological knowledge have so far been accumulated about sensory and motor functions and, further, about various higher brain functions (learning/memory, cognition, etc.). For understanding the mechanisms of such various functions achieved by complex brain networks, it is important to define the functions of individual neural pathways and to verify the impairments caused by dysfunctions of these pathways. To this end, novel techniques that can manipulate the activity of each pathway in NHPs are required. In this talk, I will introduce several experimental systems based on newly-developed viral vectors that allow discrete targeting of particular neural pathways in the primate brain.
One of the main tasks of the visual system is to combine edges and surfaces of individual objects into a perceptual group, and thus create a representation of visual scenes in which multiple objects are segregated from background. We use voltage-sensitive dye (VSD) imaging, which reflects neuronal population responses, in the primary visual cortex of behaving monkeys to investigate cortical mechanisms involved in this process. I will present our recent findings on cortical processing of shapes and surfaces and followed by stimuli reconstruction, at sub-degree resolution, from cortical activity. Next, I will describe the effects of microstimulation in the visual cortex and compare it to the responses evoked by local visual stimulation. Finally I will discuss cortical mechanisms underlying the segregation of single or few objects from background in the primary visual cortex (V1).
Understanding the working principles of the nervous system has been a major goal of modern biomedical research. The subcellular structures of neurons span across various length scales, such as tens of nanometers for synapses to centimeters for axonal projections, making it difficult to probe these components simultaneously with current technologies. Nanostructured biomaterials represent a potentially ‘imperceptible’ platform for interfacing the nervous system at unprecedented spatiotemporal scales that can circumvent the limitations of current technologies. For example, the use of nanoscale building blocks for the fabrication and assembly of next-generation brain devices facilitates packaging of higher density recording and modulating units. Additionally, as the bending stiffness of a substrate scales with material thickness to the third power, rigid and stiff materials become soft, flexible, stretchable and more biocompatible as their feature size reaches nanoscale. My lab seeks to find a non-genetic solution in minimally invasive biological modulation at multiple length scales. We use semiconductor-based nanostructured materials to understand the fundamental bioelectric dynamics of individual cells, organelles and their networks. Building on this, we have designed a set of biological modulation methods based on the light interaction with semiconductor materials and devices. Specifically, research in my lab has revealed how the physicochemical outputs from the photothermal, photofaradaic, and photocapacitive effects of nanostructured semiconductors can be identified, quantified, and utilized at semiconductor-based biointerfaces to modulate electrical activities in neurons and non-neuronal cells. This method does not require excessive wiring and can be operated with high flexibility and spatial resolution to implement multiplexed and patterned stimulations. At the end of my talk, I will discuss new materials and biological targets that could catalyze future advances.
An increasing number of studies successfully applies optogenetics in the visual system of non-human primates (NHP) in order to modulate neural activation and influence visually guided behaviour. However, it remains uncertain how optogenetic stimulation affects neural circuit activity more globally in the richly interconnected cortical and subcortical areas of the visual system and whether a visual percept can arise from such circuit activation. Here we report on experiments in which the construct AAV9-hSyn-ChR2-eYFP was injected into the primary visual cortex (V1) of four macaque monkeys. The effect of optogenetic V1 stimulation on global brain activation was assessed with functional resonance imaging (fMRI) at 4.7 T. Significant BOLD modulation was found in three monkeys in higher-order areas of extrastriate visual cortex connected with V1. Supporting experiments using electrophysiology confirmed the neural basis of this fMRI effect in V1. Behavioural tests using two-alternative forced choice procedures in one monkey established that this optogenetic stimulation could evoke a weak visual phosphene. Taken together, our results show how recruitment of activation in higher order visual cortex from V1 optogenetic stimulation can drive visual perception
The brain shows marked plasticity across a variety of learning and memory tasks as well as during recovery after injury. Many have proposed to leverage this innate plasticity using brain stimulation to treat neural disorders. Implementing such treatments requires advanced engineering tools and a thorough understanding of how stimulation-induced plasticity drives changes in network dynamics and connectivity at a large scale and across multiple brain areas. In this talk, I will cover our efforts to investigate targeted stimulation of sensorimotor cortex to drive cortical plasticity towards functional recovery. We have developed a large-scale interface consisting of state-of-the-art electrophysiology and optogenetics to simultaneously record and manipulate activity from about 5 cm2 of sensorimotor cortex in awake behaving macaques. Using this interface, for the first time, we have shown the feasibility of inducing targeted changes in sensorimotor networks using optogenetics. Furthermore, we have incorporated the capability of producing ischemic lesions in the same interface enabling us to stimulate the cortex around the site of injury and monitor functional recovery via change in blood flow, neurophysiology and behavior. Currently we are using these technologies towards developing therapeutic interventions for neurological disorders such as stroke.
The retinal image is insufficient for determining what is 'out there', because an infinitude of possible real-world objects could produce any given retinal image. Thus the visual system must infer which external cause is most likely given prior knowledge that is either innate or learned via interactions with the environment. I will describe a general framework of 'Bayesian inference' that we have used to explore the role of cortico-cortical feedback in the visual system, and I will further argue that this approach to 'seeing' makes our visual systems prone to false perceptions, or hallucinations, in a variety of different ways.
A long-term goal of sensory neuroscience is to understand the nature of the neural code in sensory cortex. To demonstrate this understanding, we need to show that we can (1) “read” the code – i.e., use neural signals from a subject’s cortex to outperform the subject in a demanding perceptual task and to account for the variability in the subject’s perceptual decisions, and (2) “write” the code – i.e., substitute sensory stimulation with artificially evoked, perceptually equivalent, neural responses. Distributed representations and topography are two key properties of primate sensory cortex. For example, in primary visual cortex (V1), the most localized stimulus can activate millions of V1 neurons that are distributed over multiple mm2, and neurons that are similarly tuned are clustered together at the sub-mm scale and form several overlaid topographic maps. The distributed and topographic nature of V1’s representations raises the possibility that in some visual tasks, the neural code in V1 operates at the topographic scale. If this were the case, then the fundamental unit of information would be clusters of similarly tuned neurons (e.g., orientation columns) rather than individual neurons, and to account for the subjects’ performance, it would be necessary and sufficient to consider the summed activity of the thousands of neurons within each cluster. The long-term goal of our research is to test the topographic population code hypothesis. In this presentation, I will discuss two studies that indirectly test the topographic population code hypothesis, and describe our progress toward developing a bi-directional, read-write, optical-genetic toolbox for directly testing this hypothesis in behaving macaques.
Follow this link to sign up and become a part of ESISyNC 2020! There is no registration fee, but places are limited.
We are looking forward to seeing you online.
Registration deadline: 10 August 2020
Poster submission deadline: 17 August 2020
The best poster will be rewarded with the ESISyNC poster prize.
esi-sync (at) esi-frankfurt.de