September 21, 2009 - August 31, 2015
Determining the properties and salience of sensory cues is fundamental to the survival and characteristic behavior of most, if not all, organisms. Our lab identifies mechanisms that underlie the sensitivity and selectivity with which neurons in the mammalian nervous system respond to visual stimuli.
Electrical activity in the central nervous system (CNS) provides a rich and remarkably precise source of information about the external world, enabling animals to distinguish molecules that differ by a single atom, wavelengths of light that vary by less than 10 billionths of a meter, and sounds originating from nearly identical locations. However, different combinations of visual (or chemical, or auditory) stimuli can elicit activity in the CNS that generates indistinguishable percepts, a property that artists (and chefs, among others) exploit frequently.
These observations raise at least two important questions: What enables, and what limits, the fidelity with which neural activity in the CNS encodes information about characteristics of sensory stimuli?
To answer these questions we identify mechanisms that govern the response of neurons and neural circuits to features of sensory stimuli. We focus on areas of the CNS in which neural activity can be modulated accurately and reproducibly by external cues and the source of stimulus-evoked synaptic input a given neuron receives is known or highly constrained; our current efforts are focused on the retina and superior colliculus, two regions in which these criteria are satisfied. While the area in which we perform experiments varies, a general question—to what degree does the sensitivity and specificity with which a neuron responds to sensory stimuli reflect intrinsic properties of that neuron versus properties of the input it receives?—permeates nearly all of our research.
For example, in the retina and superior colliculus (and other areas), electrical activity of neurons is influenced by visual stimuli emanating from particular regions of the external world. The organization, shape, and size of these regions, called receptive fields, provide an important constraint on the spatial resolution with which the origin of sensory information can be determined—i.e., given the same degree of overlap between adjacent receptive fields, spatial resolution increases as receptive field size decreases.
Receptive field size varies considerably (and often predictably) within a class of neuron as well as between distinct classes of neurons; what factors underlie these differences is largely unknown. Examining light-evoked activity in retinal ganglion cells (RGCs), the neurons through which information about all light stimuli is transmitted to the brain, provides an unusually good opportunity to distinguish the relative degree to which circuit, synaptic, and cellular properties underlie RGC receptive fields. Decades of detailed anatomical studies, and new techniques to label and manipulate specific sets of neurons, enable us to measure and control the source and properties of signals that a given RGC receives in response to physiological stimuli. Additional techniques—e.g., simultaneous patch-clamp recordings from multiple neurons; release of caged neurotransmitters via multiphoton excitation—permit us to control the temporal and spatial properties of synaptic input more precisely than is possible with light stimuli alone. Utilized together, these biological and technical features enable us to parse the relative degree to which synaptic, cellular, and network properties contribute to RGC receptive fields.
A similar approach will also help us to identify mechanisms that govern the range and specificity of light stimuli to which neurons downstream of the retina respond. In particular, we have begun to determine to what degree differences in the receptive fields of neurons in the superior colliculus reflect properties of the neurons themselves, the collicular networks in which they are embedded, and/or the characteristics and source of synaptic input they receive from RGCs. These studies will help (1) characterize the propagation and transformation of signals through multiple levels of the early visual system and (2) identify the precise circuit and cellular mechanisms that govern the sets of stimuli that do and do not elicit activity in particular classes of neurons.
Working in the superior colliculus represents a new, and exciting, direction for us. Indeed, the flexibility and resources to initiate a new research endeavor is part of what attracted us to the Janelia environment. Equally attractive is the opportunity to work directly with groups that are using distinct approaches to ask similar questions—e.g., the labs of Jeff Magee, Josh Dudman. The perspectives and techniques represented in these (and other) groups has both expanded the diversity of questions we can ask as well as increase the detail and rigor with which we can answer questions of common interest.