Brain Function: Novel Technologies Driving Novel Understanding - Bioinspired Approaches for Human-Centric Technologies - page 296

thus to test their sufficiency and necessity for a given behavior in living organisms.
Third, because so much of the adaptability and plasticity of the brain appears to
reside in synapses, we need to better characterize synaptic mechanisms and dynam-
ics over broad timescales. All these goals require the development of innovative
new experimental tools. Finally, collecting the experimental data is only the initial
step: mathematical models are needed to truly “understand” brain function, to
integrate descriptions at different levels of experimental inquiry, to reduce dimen-
sionality, to devise testable hypotheses, and ultimately to provide the essential
computational framework for brain-mimetic artificial devices.
This chapter presents a glimpse of the multidisciplinary approaches that IIT
scientists are applying to the fundamental challenge of understanding neural cir-
cuits and computations and illustrates how advanced technology and analysis at IIT
are driving discovery in neuroscience. Examples include novel optical methods to
probe neural circuits and subcellular elements, innovative micro- and nanoscale
devices to measure electrical and chemical signaling by neurons, and advanced
analytical techniques to make sense of the dizzying multi-scale complexity of the
brain. Our overarching view is that the brain overcomes the limitations of its
biological hardware by the brilliance of its architecture . If we could develop the
right tools to deduce that architecture, we could begin to meaningfully mimic the
functionality of the brain.
10.1 Mapping Brain Electrical Activity at Cellular
Resolution with Light
A prerequisite to understand the function of specific brain areas is to describe how
specific cells in a brain area respond in space and time in a given behavioral context.
As discussed in Chap. 9 , electrophysiology has long been the preferred method for
studying the central nervous system because of its excellent temporal resolution and
because of its ability to capture a wide range of neural phenomena, from the
millisecond-precision spiking activity of individual neurons and small populations
to slower network oscillations (see later in this chapter for innovative new
approaches for massively parallel electrophysiological techniques). However, the
use of fluorescent indicators in combination with two-photon microscopy is now
recognized as an equally fundamental tool for brain circuit analysis in vivo. For
example, the development of fluorescent calcium indicators (Tsien 1980 , 1981 )not
only revealed the roles of calcium ion as a second messenger but also allowed the
monitoring of the activity of neurons, using the entry of calcium ions as proxy for
electrical activity. In neurons, the depolarization that underlies an action potential
opens voltage-gated calcium channels, leading to significant calcium accumulation
in the intracellular space (Helmchen et al. 1996 ; Svoboda et al. 1997 ; Borst and
Helmchen 1998 ). Intracellular calcium concentration can thus be used as an indirect
measure of the suprathreshold activity of neurons. Moreover, fluorescence calcium