Associate Professor, Department of Biology
Ph.D. Stanford University
B.S. Stanford Univeristy
Research Interests: Function and development of neural circuits for visual processing
Overview: How do we make sense of the visual world around us? Our brain takes a pattern of photons hitting the retina and continually creates a coherent representation of what we see – detecting objects and landmarks rather than just perceiving an array of pixels. This image processing allows us to perform a range of visual tasks, such as recognizing a friend’s face, finding your way to the grocery store, and catching a frisbee. However, how these computational feats are achieved by the neural circuitry of the visual system is largely unknown. Furthermore, this circuitry is wired up by a range of cellular processes, such as arbor growth, synapse formation, and activity-dependent plasticity, and thus these developmental mechanisms effectively determine how we see the world.
Our research is focused on understanding how neural circuits perform the image processing that allows us to perform complex visual behaviors, and how these circuits are assembled during development. We use in vivo recording techniques, including high-density extracellular recording and two-photon imaging, along with molecular genetic tools to dissect neural circuits, such as cell-type specific markers, optogenetic activation and inactivation, tracing of neural pathways, and in vivo imaging of dendritic and synaptic structure. We have also implemented behavioral tasks for mice so we can perform quantitative pyschophysics to measure the animal’s perception, and we use theoretical models to understand general computational principles being instantiated by a neural circuit.
Changes in white matter in mice resulting from low-frequency brain stimulation.
Proc Natl Acad Sci U S A. 2018 Jun 18;:
Authors: Piscopo DM, Weible AP, Rothbart MK, Posner MI, Niell CM
Recent reports have begun to elucidate mechanisms by which learning and experience produce white matter changes in the brain. We previously reported changes in white matter surrounding the anterior cingulate cortex in humans after 2-4 weeks of meditation training. We further found that low-frequency optogenetic stimulation of the anterior cingulate in mice increased time spent in the light in a light/dark box paradigm, suggesting decreased anxiety similar to what is observed following meditation training. Here, we investigated the impact of this stimulation at the cellular level. We found that laser stimulation in the range of 1-8 Hz results in changes to subcortical white matter projection fibers in the corpus callosum. Specifically, stimulation resulted in increased oligodendrocyte proliferation, accompanied by a decrease in the g-ratio within the corpus callosum underlying the anterior cingulate cortex. These results suggest that low-frequency stimulation can result in activity-dependent remodeling of myelin, giving rise to enhanced connectivity and altered behavior.
PMID: 29915074 [PubMed - as supplied by publisher]
Seeing with a biased visual cortical map.
J Neurophysiol. 2018 May 09;:
Authors: Mazade R, Niell CM, Alonso JM
PMID: 29742024 [PubMed - as supplied by publisher]
Refinement of spatial receptive fields in the developing mouse LGN is coordinated with excitatory and inhibitory remodeling.
J Neurosci. 2018 Apr 16;:
Authors: Tschetter WW, Govindaiah G, Etherington IM, Guido W, Niell CM
Receptive field properties of individual visual neurons are dictated by the precise patterns of synaptic connections they receive, including the arrangement of inputs in visual space and features such as polarity (On versus Off). The inputs from retina to the lateral geniculate nucleus (LGN) in the mouse undergo significant refinement over development, however it is unknown how this corresponds to the establishment of functional visual response properties. Here we conducted in vivo and in vitro recordings in mouse LGN, beginning just after natural eye opening to determine how receptive fields develop as excitatory and feed-forward inhibitory retinal afferents refine. Experiments used both male and female subjects. For in vivo assessment of receptive fields, we performed multisite extracellular recordings in awake mice. Spatial receptive fields were over twice as large at eye-opening as in adults, and then reduced in size over the subsequent week. This topographic refinement was accompanied by other spatial changes such as a decrease in spot size preference and an increase in surround suppression. Notably, the degree of specificity in terms of On/Off and sustained/transient responses appeared to be established already at eye opening and did not change. During the same time, in vitro recordings of the synaptic responses evoked by optic tract stimulation revealed a pairing of decreased excitatory and increased feed-forward inhibitory convergence, providing a potential mechanism to explain the spatial receptive field refinement.SIGNIFICANCE STATEMENTThe development of precise patterns of retinogeniculate connectivity has been a powerful model system for understanding the mechanisms underlying the activity dependent refinement of sensory systems. Here we link the maturation of spatial receptive field properties in dLGN to the remodeling of retinal and inhibitory feed-forward convergence onto dLGN neurons. These findings should thus provide a foundation to test the cell-type specific plasticity mechanisms that lead to refinement of different excitatory and inhibitory inputs, and their impact on the establishment of mature receptive fields in the LGN.
PMID: 29661964 [PubMed - as supplied by publisher]