Biomedical subjects

Thomas D Mrsic-Flogel

Publications and source records attributed to Thomas D Mrsic-Flogel.

9 recordsLinked to original sources

PubMed2006

Lifelong learning: ocular dominance plasticity in mouse visual cortex.

Ocular dominance plasticity has long served as a successful model for examining how cortical circuits are shaped by experience. In this paradigm, altered retinal activity caused by unilateral eye-lid closure leads to dramatic shifts in the binocular response properties of neurons in the visual cortex. Much of the recent progress in identifying the cellular and molecular mechanisms underlying ocular dominance plasticity has been achieved by using the mouse as a model system. In this species, monocular deprivation initiated in adulthood also causes robust ocular dominance shifts. Research on ocular dominance plasticity in the mouse is starting to provide insight into which factors mediate and influence cortical plasticity in juvenile and adult animals.

Animals↗

PubMed2006

Development of contralateral and ipsilateral frequency representations in ferret primary auditory cortex.

Little is known about the maturation of functional maps in the primary auditory cortex (A1) after the onset of sensory experience. We used intrinsic signal imaging to examine the development of the tonotopic organization of ferret A1 with respect to contralateral and ipsilateral tone stimulation. Sound-evoked responses were recorded as early as postnatal day (P) 33, a few days after hearing onset. From P36 onwards, pure tone stimuli evoked restricted, tonotopically organized patches of activity. There was an age-dependent increase in the cortical area representing each octave, with a disproportionate expansion of cortical territory representing frequencies > 4 kHz after P60. Similar tonotopic maps were observed following stimulation of the contralateral and ipsilateral ears. During the first few weeks following hearing onset, no differences were found in the area of cortical activation or in the magnitude of the optical responses evoked by stimulation of each ear. In older animals, however, contralateral stimuli evoked stronger responses and activated a larger A1 area than ipsilateral stimuli. Our findings indicate that neither the tonotopic organization nor the representation of inputs from each ear reach maturity until approximately 1 month after hearing onset. These results have important implications for cortical signal processing in juvenile animals.

Acoustic Stimulation↗

PubMed2005

Prior experience enhances plasticity in adult visual cortex.

The brain has a remarkable capacity to adapt to alterations in its sensory environment, which is normally much more pronounced in juvenile animals. Here we show that in adult mice, the ability to adapt to changes can be improved profoundly if the mouse has already experienced a similar change in its sensory environment earlier in life. Using the standard model for sensory plasticity in mouse visual cortex-ocular dominance (OD) plasticity-we found that a transient shift in OD, induced by monocular deprivation (MD) earlier in life, renders the adult visual cortex highly susceptible to subsequent MD many weeks later. Irrespective of whether the first MD was experienced during the critical period (around postnatal day 28) or in adulthood, OD shifts induced by a second MD were faster, more persistent and specific to repeated deprivation of the same eye. The capacity for plasticity in the mammalian cortex can therefore be conditioned by past experience.

Aging↗

PubMed2005

Regulation of EphA 4 kinase activity is required for a subset of axon guidance decisions suggesting a key role for receptor clustering in Eph function.

Signaling by receptor tyrosine kinases (RTKs) is mediated by their intrinsic kinase activity. Typically, kinase-activating mutations result in ligand-independent signaling and gain-of-function phenotypes. Like other RTKs, Ephs require kinase activity to signal, but signaling by Ephs in vitro also requires clustering by their membrane bound ephrin ligands. The relative importance of Eph kinase activity and clustering for in vivo functions is unknown. We find that knockin mice expressing a mutant form of EphA4 (EphA4(EE)), whose kinase is constitutively activated in the absence of ephrinB ligands, are deficient in the development of thalamocortical projections and some aspects of central pattern generator rhythmicity. Surprisingly, other functions of EphA4 were regulated normally by EphA4(EE), including midline axon guidance, hindlimb locomotion, in vitro growth cone collapse, and phosphorylation of ephexin1. These results suggest that signaling of Eph RTKs follows a multistep process of induced kinase activity and higher-order clustering different from RTKs responding to soluble ligands.

Animals↗

PubMed2005

Altered map of visual space in the superior colliculus of mice lacking early retinal waves.

During the development of the mammalian retinocollicular projection, a coarse retinotopic map is set up by the graded distribution of axon guidance molecules. Subsequent refinement of the initially diffuse projection has been shown to depend on the spatially correlated firing of retinal ganglion cells. In this scheme, the abolition of patterned retinal activity is not expected to influence overall retinotopic organization, but this has not been investigated. We used optical imaging of intrinsic signals to visualize the complete retinotopic map in the superior colliculus (SC) of mice lacking early retinal waves, caused by the deletion of the beta2 subunit of the nicotinic acetylcholine receptor. As expected from previous anatomical studies in the SC of beta2(-/-) mice, regions activated by individual visual stimuli were much larger and had less sharp borders than those in wild-type mice. Importantly, however, we also found systematic distortions of the entire retinotopic map: the map of visual space was expanded anteriorly and compressed posteriorly. Thus, patterned neuronal activity in the early retina has a substantial influence on the coarse retinotopic organization of the SC.

Animals↗

PubMed2005

Encoding of virtual acoustic space stimuli by neurons in ferret primary auditory cortex.

Recent studies from our laboratory have indicated that the spatial response fields (SRFs) of neurons in the ferret primary auditory cortex (A1) with best frequencies > or =4 kHz may arise from a largely linear processing of binaural level and spectral localization cues. Here we extend this analysis to investigate how well the linear model can predict the SRFs of neurons with different binaural response properties and the manner in which SRFs change with increases in sound level. We also consider whether temporal features of the response (e.g., response latency) vary with sound direction and whether such variations can be explained by linear processing. In keeping with previous studies, we show that A1 SRFs, which we measured with individualized virtual acoustic space stimuli, expand and shift in direction with increasing sound level. We found that these changes are, in most cases, in good agreement with predictions from a linear threshold model. However, changes in spatial tuning with increasing sound level were generally less well predicted for neurons whose binaural frequency-time receptive field (FTRF) exhibited strong excitatory inputs from both ears than for those in which the binaural FTRF revealed either a predominantly inhibitory effect or no clear contribution from the ipsilateral ear. Finally, we found (in agreement with other authors) that many A1 neurons exhibit systematic response latency shifts as a function of sound-source direction, although these temporal details could usually not be predicted from the neuron's binaural FTRF.

Acoustic Stimulation↗

PubMed2005

Encoding stimulus information by spike numbers and mean response time in primary auditory cortex.

Neurons can transmit information about sensory stimuli via their firing rate, spike latency, or by the occurrence of complex spike patterns. Identifying which aspects of the neural responses actually encode sensory information remains a fundamental question in neuroscience. Here we compared various approaches for estimating the information transmitted by neurons in auditory cortex in two very different experimental paradigms, one measuring spatial tuning and the other responses to complex natural stimuli. We demonstrate that, in both cases, spike counts and mean response times jointly carry essentially all the available information about the stimuli. Thus, in auditory cortex, whereas spike counts carry only partial information about stimulus identity or location, the additional availability of relatively coarse temporal information is sufficient in order to extract essentially all the sensory information available in the spike discharge pattern, at least for the relatively short stimuli (<approximately 100 ms) commonly used in auditory research.

Acoustic Stimulation↗

PubMed2003

Acoustic factors govern developmental sharpening of spatial tuning in the auditory cortex.

Auditory localization relies on the detection and interpretation of acoustic cues that change in value as the head and external ears grow. Here we show that the maturation of these structures is an important determinant for the development of spatial selectivity in the ferret auditory cortex. Spatial response fields (SRFs) of high-frequency cortical neurons recorded at postnatal days (P) 33-39 were broader, and transmitted less information about stimulus direction, than in older ferrets. They also exhibited slightly broader frequency tuning than neurons recorded in adult animals. However, when infant neurons were stimulated through virtual ears of adults, SRFs sharpened significantly and the amount of transmitted information increased. This improvement was predicted by a model that generates SRF shape from the localization cue values and the neurons' binaural spectrotemporal response properties. The maturation of spatial response characteristics in auditory cortex therefore seems to be limited by peripheral rather than by central factors.

Acoustic Stimulation↗

PubMed2002

Optical imaging of intrinsic signals in ferret auditory cortex: responses to narrowband sound stimuli.

This paper describes optical imaging of the auditory cortex in the anesthetized ferret, particularly addressing optimization of narrowband stimuli. The types of sound stimuli used were tone-pip trains and sinusoidal frequency and amplitude modulated (SFM and SAM) tones. By employing short illumination wavelengths (546 nm), we have successfully characterized the tonotopic arrangement, in agreement with the well-established electrophysiological tonotopic maps of the ferret auditory primary field (AI). The magnitude of the optical signal increased with sound level, was maximal for a modulation frequency (MF) of 2-4 Hz, and was larger for tone-pip trains and SFM sounds than for SAM sounds. Accordingly, an optimal narrowband stimulus was defined. Thus optical imaging can be used successfully to obtain frequency maps in auditory cortex by an appropriate choice of stimulus parameters. In addition, background noise consisting of 0.1-Hz oscillations could be reduced by introduction of blood pressure enhancing drugs. The optical maps were largely independent of 1) the type of narrowband stimulus, 2) the sound level, and 3) the MF. This stability of the optical maps was not predicted from the electrophysiological literature.

Acoustic Stimulation↗