David W. Tank

Henry L. Hillman Professor in Molecular Biology
Professor of Molecular Biology and Princeton Neuroscience Institute

Co-Director, Princeton Neuroscience Institute

David W. Tank

lab Tank Research Lab
Phone (609) 258-7371
locationPrinceton Neuroscience Institute, 156
Phone Lab (609) 258-7371
Faculty Assistant
lisa Glass
Phone (609) 258-7365

Research Focus

Measurement and analysis of neural circuit dynamics

Action potentials are a nearly universal form of electrochemical dynamics in single neurons that result from the coordinated interaction of thousands of ion channel protein molecules. The characterization of the ionic current components of the action potential and the Hodgkin/Huxley equations describing how these currents interact were milestones in the history of experimental biophysics and quantitative modeling of biological dynamics. Are there analogous forms of "universal dynamics" produced in neural circuits by the synaptic connections and feedback loops ubiquitous in brain anatomy? Can they be understood by the use of mathematical models like those developed for the action potential? These are the key questions that drive research in my laboratory.

Our current focus is on persistent neural activity, a form of neural circuit dynamics that is associated with short-term memory. Persistent neural activity is a sustained increase or suppression of action potential firing elicited by a brief sensory stimulus or motor command. Across the population of participating neurons, the pattern of sustained changes in action potential firing is correlated with the information held in short term memory, while disruption of persistent activity produces deficits in memory-guided behavior. These characteristics suggest that the memory is actually the dynamic state of the circuit. Originally described in the frontal cortex of awake behaving primates during behaviors requiring short term retention of a sensory stimulus, persistent neural activity has also been observed in subcortical brain areas, such as the basal ganglia, superior colliculus, and brainstem. It has been observed not only in primates, but also in the thalamus, hippocampus, and midbrain of rodents as well as the brainstem of non-mammalian vertebrates. This wide diversity of brain areas and species motivates the idea that persistent neural activity may indeed represent a very general form of brain dynamics, perhaps as fundamental to neural circuits as the action potential is to single neuron dynamics.

We study the mechanisms of persistent neural activity in experimental preparations that allow advanced electrophysiological, imaging, and genetic techniques to be applied. One neural system we study is the oculomotor neural integrator. In this brainstem circuit, brief motor commands that move an eye rapidly produce persistent neural activity that is used to hold the eye in the new fixation position: the persistent activity represents a short term memory the angular position of the eye in the orbit. We study this circuit in the awake behaving goldfish where sharp and patch intracellular microelectrode recording techniques can be used to characterize electrophysiological events in neurons during persistent activity. We also employ multi-electrode recording techniques to measure statistical correlations in firing produced by synaptic interactions, and study the biophysical properties of integrator neurons in brain slice preparations. Many of our experiments are designed to test the hypothesis that persistent activity is produced by positive feedback implemented by recurrent excitation through synaptic connections and to explore the importance of particular synaptic currents such as those mediated by the NMDA receptor. Experimental results are compared with mathematical models and numerical simulations of biophysically-realistic neural network models of the goldfish integrator. We are also studying a similar circuit in the zebrafish oculomotor system, which, in the future, should allow genetic manipulations useful in testing hypothesized mechanisms of persistent neural activity. A second system we study in which genetic dissection of persistent neural activity may be possible is the head direction cell circuit in the mouse. In this circuit persistent neural activity represents a short term memory of the direction of the head relative to landmarks in the environment. This system is critically important in navigation and the current view is that it represents one component of the "sense of direction."

My laboratory is also involved in the general development of methodologies and instrumentation that can provide measurements of chemical and electrical dynamics of neurons in vivo. Considerable progress has been made in the adaptation of two-photon laser scanning microscopy for the study of calcium concentration dynamics in dendrites and nerve terminals in intact neural circuits, including the mammalian neocortex. In the future we hope to further develop and use these methods to study chemical and electrical changes in neurons during persistent neural activity.

Selected Publications

Scott BB, Constantinople CM, Erlich JC, Tank DW, Brody CD. (2015) Sources of noise during accumulation of evidence in unrestrained and voluntarily head-restrained rats. Elife. [Epub ahead of print]

Kim CK, Miri A, Leung LC,...Tank DW, Burdine RD. (2014) Prolonged, brain-wide expression of nuclear-localized GCaMP3 for functional circuit mapping. Front Neural Circuits. 8:138.  Pubmed

Low RJ, Gu Y, Tank DW. (2014) Cellular resolution optical access to brain regions in fissures: Imaging medial prefrontal cortex and grid cells in entorhinal cortex. Proc Natl Acad Sci. 111:18739-44. Pubmed

Rickgauer JP, Deisseroth K, Tank DW. (2014) Simultaneous cellular-resolution optical perturbation and imaging of place cell firing fields. Nat Neurosci. 17: 1816-24. Pubmed

Aronov D, Tank DW. (2014) Engagement of neural circuits underlying 2D spatial navigation in a rodent virtual reality system. Neuron. 84: 442-56. Pubmed

Scott BB, Brody CD, Tank DW. (2013) Cellular resolution functional imaging in behaving rats using voluntary head restraint. Neuron. 80: 371-84. Pubmed

Domnisoru C, Kinkhabwala AA, Tank DW. (2013) Membrane potential dynamics of grid cells. Nature. 495: 199-204. Pubmed

Drocco JA, Wieschaus EF, Tank DW. (2012) The synthesis-diffusion-degradation model explains Bicoid gradient formation in unfertilized eggs. Phys Biol.  9: 055004. Pubmed

Ozden I, Dombeck DA, Hoogland TM, Tank DW, Wang SS. (2012) Widespread state-dependent shifts in cerebellar activity in locomoting mice. PLoS One. 7: e42650. Pubmed

Harvey CD, Coen P, Tank DW. (2012) Choice-specific sequences in parietal cortex during a virtual-navigation decision task. Nature. 484: 62-68. PubMed

Drocco JA, Grimm O, Tank DW, Wieschaus E. (2011) Measurement and perturbation of morphogen lifetime: effects on gradient shape. Biophys J. 101: 1807-15. PubMed

Miri A, Daie K, Arrenberg AB, Baier H, Aksay E, Tank DW. (2011) Spatial gradients and multidimensional dynamics in a neural integrator circuit. Nat Neurosci. 14: 1150-59. PubMed

Miri A, Daie K, Burdine RD, Aksay E, Tank DW. (2011) Regression-based identification of behavior-encoding neurons during large-scale optical imaging of neural activity at cellular resolution. J Neurophysiol. 105: 964-80. PubMed

Dombeck DA, Harvey CD, Tian L, Looger LL, Tank DW. (2010) Functional imaging of hippocampal place cells at cellular resolution during virtual navigation. Nat Neurosci. 13: 1433-40. PubMed

Dombeck DA, Graziano MS, Tank DW. (2009) Functional clustering of neurons in motor cortex determined by cellular resolution imaging in awake behaving mice. J Neurosci. 29: 13751-60. PubMed

McCarthy KM, Tank DW, Enquist LW. (2009) Pseudorabies virus infection alters neuronal activity and connectivity in vitro. PLoS Pathog. 5: e1000640. PubMed

Harvey CD, Collman F, Dombeck DA, Tank DW. (2009) Intracellular dynamics of hippocampal place cells during virtual navigation. Nature. 461: 941-46. PubMed

Rickgauer JP, Tank DW. (2009) Two-photon excitation of channelrhodopsin-2 at saturation. Proc Natl Acad Sci. 106: 15025-30. PubMed

Markowitz DA, Collman F, Brody CD, Hopfield JJ, Tank DW. (2008) Rate-specific synchrony: using noisy oscillations to detect equally active neurons. Proc Natl Acad Sci. 105: 8422-27. PubMed

Major G, Polsky A, Denk W, Schiller J, Tank DW. (2008) Spatiotemporally graded NMDA spike/plateau potentials in basal dendrites of neocortical pyramidal neurons. J Neurophysiol. 99: 2584-601. PubMed

Gregor T, Tank DW, Wieschaus EF, Bialek W. (2007) Probing the limits to positional information. Cell. 130: 153-64. PubMed

Dombeck DA, Khabbaz AN, Collman F, Adelman TL, Tank DW. (2007) Imaging large-scale neural activity with cellular resolution in awake, mobile mice. Neuron. 56: 43-57. PubMed

Gregor T, Wieschaus EF, McGregor AP, Bialek W, Tank DW. (2007) Stability and nuclear dynamics of the bicoid morphogen gradient. Cell. 130: 141-52. PubMed

Aksay E, Olasagasti I, Mensh BD, Baker R, Goldman MS, Tank DW. (2007) Functional dissection of circuitry in a neural integrator. Nat Neurosci. 10: 494-504. PubMed

Gregor T, Bialek W, de Ruyter van Steveninck RR, Tank DW, Wieschaus EF. (2005) Diffusion and scaling during early embryonic pattern formation. Proc Natl Acad Sci. 102: 18403-07. PubMed

Major G, Baker R, Aksay E, Seung HS, Tank DW. (2004) Plasticity and tuning of the time course of analog persistent firing in a neural integrator. Proc Natl Acad Sci. 101: 7745-50. PubMed

Major G, Baker R, Aksay E, Mensh B, Seung HS, Tank DW. (2004) Plasticity and tuning by visual feedback of the stability of a neural integrator. Proc Natl Acad Sci. 101: 7739-44. PubMed

Aksay E, Baker R, Seung HS, Tank DW. (2003) Correlated discharge among cell pairs within the oculomotor horizontal velocity-to-position integrator. J Neurosci. 23: 10852-58. PubMed

Aksay E, Major G, Goldman MS, Baker R, Seung HS, Tank DW. (2003) History dependence of rate covariation between neurons during persistent activity in an oculomotor integrator. Cereb Cortex. 13: 1173-84. PubMed

Aksay E, Gamkrelidze G, Seung HS, Baker R, Tank DW. (2001) In vivo intracellular recording and perturbation of persistent activity in a neural integrator. Nat Neurosci. 4: 184-93. PubMed

Seung HS, Lee DD, Reis BY, Tank DW. (2000) The autapse: a simple illustration of short-term analog memory storage by tuned synaptic feedback. J Comput Neurosci. 9: 171-85. PubMed

Seung HS, Lee DD, Reis BY, Tank DW. (2000) Stability of the memory of eye position in a recurrent network of conductance-based model neurons. Neuron. 26: 259-71. PubMed

Aksay E, Baker R, Seung HS, Tank DW. (2000) Anatomy and discharge properties of pre-motor neurons in the goldfish medulla that have eye-position signals during fixations. J Neurophysiol. 84: 1035-49. PubMed

Svoboda K, Denk W, Kleinfeld D, Tank DW. (1997) In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature. 385: 161-65. PubMed

Tank DW, Regehr WG, Delaney KR. (1995) A quantitative analysis of presynaptic calcium dynamics that contribute to short-term enhancement. J Neurosci. 15: 7940-52. PubMed

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