Emerging Techniques in Neuroscience

Coordinators: Adrienne Fairhall, David Kleinfeld, Fred Wolf

Scientific Advisors: Charles Stevens

This program aims to bring together theorists with researchers driving the frontiers of experimental neuroscience in order to identify and stimulate new directions in understanding principles of brain function.

The computational abilities of biological nervous systems are based on the dynamics of the underlying neurons and networks. While idealized models of these complex dynamical systems have been a focus of theoretical work in physics and neuroscience over the past two and a half decades, there is occurring an explosive growth of powerful experimental tools to interface with, manipulate, and control the dynamics of neurons and networks with a spatiotemporal precision that matches the microscopic organization of biological nervous systems. On the level of single neurons, fast multi-site uncaging of neurotransmitter applied to dendritic arbors in vitro can mimic the complex distributed patterns of synaptic inputs received in vivo, allowing the experimenter to probe the machinery of nonlinear dendritic processing and plasticity. Genetically encoded light-gated ion channels and pumps now allow the control of precise temporal patterning of nerve impulses in specific groups of neurons in the brains of freely behaving animals. New optical methods and reconstruction techniques allow the delineation of wiring diagrams of neural and vascular networks.

These emerging techniques alongside the rapid accumulation of anatomical information are driving a revolutionary change in neuroscience experimentation, enabling many long standing questions about the mechanisms and principles of neuronal dynamics in quantitative experiments to be addressed for the first time. Thus, it is timely to bring together theorists, experimental biophysicists, and cellular and systems neuroscientists to lay out an agenda for the next round of discovery, both to set priorities for experimental directions based on theoretically framed questions and to examine where theory is lacking, given the questions now or soon able to be pursued experimentally.

On the cellular level: key questions include: What is the role of subcellular organization, such as active dendrites and multiple action potential initiation zones, in shaping single neuron dynamics and function? How can one deduce or identify faithful effective models for single neuron computation under naturalistic operating conditions? How does spatial morphology contribute to the computational capability of individual neurons?

On the network level: Can one achieve effective control of network state by control or inactivation of a structurally defined subsystem? Do cortical networks exhibit structural motifs that define a heterogeneous susceptibility of their dynamics to external perturbation? What information is emerging from connectome projects to define anatomy first at the level of pathways and later at the level of individual neuronal connections? How can one make sense of it to advance our understanding of brain processing?

At the systems level: Can one use the intrinsic plasticity of neuronal processing architectures to reprogram functional connectivity with spatiotemporally structured neurostimulation? How can one use the approaching ability to open and restore brain feedback loops to make progress in understanding the algorithms of sensorimotor control? How can one reproduce these algorithms to develop functional neural prostheses?

Our goal is to bring together theorists working at and across many levels of description in neuronal systems with the experimentalists who are developing and applying new tools. We hope to provoke a lively, forward-thinking dialogue about the opportunities posed by these technical developments for both experiment and theory.

Weekly Schedule

Especially for the sake of experimentalists who can only come for short visits, we provide a tentative schedule of topics by week below.  The final schedule will be determined in part by the availability of the relevant participants.

Week 1

9/20-9/24

Opening talks: The technological face of neuroscience

  • Optics (super-resolution; deep imaging)
  • MRI (fMRI, DRI)
  • EM (automated methods; correlated light/EM)
  • High throughput behavioral analysis
  • Genetic models of behavior, neurological and psychiatric disorders
  • High throughput electrophysiology, optogenetics
  • High throughput anatomy (connectomes, proteomes, …)

Week 2

9/26-10/1

Network dynamics

  • Propagating activity
  • The potential role of correlations in coding and computation

Week 3

10/4-10/8

Dendritic computation

  • Large-scale spatiotemporal integration in dendrites
  • Mapping logical functions onto dendrites

Week 4

10/11-10/15

Single cell dynamics and computation

  • Adaptation and state-dependent properties, models for single cell computation, relationship between single cell and circuit function.

Week 5

10/18-10/22

Network computation

  • Computation in canonical microcircuits
  • Coding and information flow

Week 6

10/25-10/29

Control in networks

  • Cultured networks
  • Vascular networks, neuronal and glial control of flow

Week 7

11/1-11/5

Network plasticity

  • Reorganization of networks during development and after trauma

Week 8

11/8-11/12

Sensorimotor processing

  • Coordinate transforms from sensation to action, flight control