By taking advantage of recent advances in two-photon microscopy, the research in my lab addresses
three broad aims, with a particular focus on the function, development and plasticity of primary
visual cortex: 1) to understand how cortical neuronal networks encode visual information,
2) to understand how they become specialised for sensory processing during postnatal development,
and 3) to investigate how experiences influence the structure and function of cortical circuits.
We use in vivo two-photon calcium imaging to record activity simultaneously from hundreds of
neurons in visual cortex while showing different visual stimuli. This approach enables us to
characterise in detail how neuronal activity is distributed in space and time within a cortical
column and how individual neurons and neuronal subsets interact within a large cortical network
in response to visual stimuli. We investigate the maturation of cortical network function after
the onset of vision and assess the role of visual experience in this process. We are now aiming
to correlate population responses with the behavior of the animal, in order to understand how
network activity relates to the animal´s perception. Moreover, genetic labeling of different
neuronal subtypes allows us to address the role of different cell classes in sensory processing.
Finally, by means of high-resolution two-photon time-lapse imaging of individual synapses
(dendritic spines) over the course of days to weeks, we can visualize how synaptic connectivity
changes during development, during novel sensory experiences and after learning.
Together, this knowledge will contribute to our understanding of how circuits in the cerebral
cortex processes sensory information and how they adapt to an ever changing environment.

1.       Holtmaat A, Bonhoeffer T, Chow DK, Chuckowree J, De Paola V, Hofer SB, Hübener M, Keck T, Knott G, Lee WC, Mostany R, Mrsic-Flogel TD, Nedivi E, Portera-Cailliau C, Svoboda K, Trachtenberg JT, Wilbrecht L. (2009) Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat Protoc 4: 1128-44.

2.       Hofer SB, Mrsic-Flogel TD, Bonhoeffer T, Hübener M. (2009). Experience leaves a lasting structural trace in cortical circuits. Nature. 15;457:313-7.

3.       Keck T, Mrsic-Flogel TD, Vaz Afonso M, Eysel UT, Bonhoeffer T, Hübener M (2008) Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex. Nat Neurosci. 11: 1162-7.

4.       Chakravarthy S, Keck T, Roelandse M, Hartman R, Jeromin A, Perry S, Hofer SB, Mrsic-Flogel T, Levelt CN (2008) Cre-dependent expression of multiple transgenes in isolated neurons of the adult forebrain. PLoS ONE. 3: e3059.

5.       Mank M, Santos AF, Direnberger S, Mrsic-Flogel TD, Hofer SB, Stein V, Hendel T, Reiff DF, Levelt C, Borst A, Bonhoeffer T, Hübener M, Griesbeck O. A genetically encoded calcium indicator for chronic in vivo two-photon imaging. Nat Methods 5: 805-11.

6.       Mrsic-Flogel TD, Hofer SB, Ohki K, Reid RC, Bonhoeffer T, Hübener M (2007) Homeostatic regulation of eye-specific responses in visual cortex during ocular dominance plasticity. Neuron 54: 961-72.

7.       Hofer SB, Mrsic-Flogel TD, Bonhoeffer T, Hübener M (2006) Lifelong learning: Ocular dominance plasticity in mouse visual cortex. Curr Opin Neurobiol 16: 451‑9.

8.       Hofer SB, Mrsic-Flogel TD, Bonhoeffer T, Hübener M (2006) Prior experience enhances plasticity in adult visual cortex. Nature Neurosci 9: 127-32.

9.       Mrsic-Flogel TD, Versnel H, King AJ. (2006) Development of contralateral and ipsilateral frequency representations in the ferret primary auditory cortex. Eur J Neurosci 23: 780-792.

10.   Mrsic-Flogel TD, Hofer SB, Creutzfeldt C, Cloëz-Tayarani I, Changeux JP, Bonhoeffer T, Hübener M (2005) Altered map of visual space in the superior colliculus of mice lacking early retinal waves. J Neurosci 25: 6921-8.

11.   Mrsic-Flogel TD, King AJ, Schnupp JWH (2005) Encoding of virtual acoustic space stimuli by neurons in ferret primary auditory cortex. J Neurophysiol  93: 3489-3503.

12.   Nelken I, Chechik G, Mrsic-Flogel TD, King AJ, Schnupp JWH (2005) Spike count and mean response time jointly carry all stimulus information in primary auditory cortex. J Comput Neurosci 19: 199-221.

13.   Egea J, Vig Nissen U, Dufour A, Sahin M, Greer P, Kullander K, Mrsic-Flogel TD, Greenberg ME, Kiehn O, Vanderhaeghen P, Klein R (2005) Regulation of EphA4 kinase activity is required for thalamocortical but not midline axon pathfinding - additional role of receptor clustering in Eph function. Neuron 47: 515-528.

14.   Mrsic-Flogel TD, Schnupp JWH, King AJ (2003) Acoustic factors govern developmental sharpening of spatial tuning in the auditory cortex. Nature Neurosci 6: 981-988.

15.   Mrsic-Flogel T, Hübener M, Bonhoeffer T (2003) Brain mapping: New wave optical imaging. Current Biology 13: R778-R780.

16.   Mrsic-Flogel T, Hübener M (2002) Visual cortex: Suppression by depression. Current Biology 12: R547-R549.

17.   Versnel H, Mossop JE, Mrsic-Flogel TD, Moore DR (2002) Optical imaging of intrinsic signals in ferret auditory cortex: responses to narrow-band sound stimuli. J Neurophysiol 88: 1545-1558.

18.   Mrsic-Flogel TD, King AJ, Jenison RL, Schnupp JWH (2001) Listening through different ears alters spatial receptive fields in ferret primary auditory cortex. J Neurophysiol 86: 1043-6.

19.   Schnupp JWH, Mrsic-Flogel TD, King AJ (2001) Linear processing of spatial cues in primary auditory cortex. Nature 414: 200-4.  

20.   King AJ, Kacelnik O, Mrsic-Flogel TD, Schnupp JWH, Parsons CH, Moore DR (2001) How plastic is spatial hearing? Audiol Neuro-Otol 6: 182-6.

21.   Ledig MM, McKinnell IW, Mrsic-Flogel T, Wang J, Alvares C, Mason I, Bixby JL, Mueller BK, Stoker AW (1999) Expression of receptor tyrosine phosphatases during development of the retinotectal projection of the chick. J Neurobiol 39: 81-96

Two-photon laser scanning miscroscopy of in vivo prepaprations:

- in vivo calcium imaging of neuronal populations with single-cell resolution

- repeated in vivo imaging dendritic and axonal structures

Electrophysiology in vivo

- single- and multi-unit recordings in the visual and auditory cortex

Intrinsic signal imaging