Dynamics of spatial frequency tuning in mouse visual cortex

Neuronal spatial frequency tuning in primary visual cortex (V1) substantially changes over time. In both primates and cats, a shift of the neuron\u27s preferred spatial frequency has been observed from low frequencies early in the response to higher frequencies later in the response. In most cases, this shift is accompanied by a decreased tuning bandwidth. Recently, the mouse has gained attention as a suitable animal model to study the basic mechanisms of visual information processing, demonstrating similarities in basic neuronal response properties between rodents and highly visual mammals. Here we report the results of extracellular single-unit recordings in the anesthetized mouse where we analyzed the dynamics of spatial frequency tuning in V1 and the lateromedial area LM within the lateral extrastriate area V2L. We used a reverse-correlation technique to demonstrate that, as in monkeys and cats, the preferred spatial frequency of mouse V1 neurons shifted from low to higher frequencies later in the response. However, this was not correlated with a clear selectivity increase or enhanced suppression of responses to low spatial frequencies. These results suggest that the neuronal connections responsible for the temporal shift in spatial frequency tuning may considerably differ between mice and monkeys

Functional characterization of cortical plasticity in the visual cortex of adult mice

Neuroplasticity is the mammalian brain’s capability to adapt structurally and functionally to changing inputs from the environment. It allows the brain to develop, learn and remember or to recover from injury to the central or peripheral nervous system. Partial or complete sensory loss can as such be compensated by the spared part of the affected modality (unimodal plasticity) or by other non-injured senses (cross-modal plasticity). In young animals these processes have been studied intensively in the context of blindness or early vision loss over the last decades. However, in recent years our research group gathered evidence that also in adulthood, upon surgically induced irreversible loss of vision through one eye (monocular enucleation, ME), mice are capable to reactivate their affected visual cortex in a time course of seven weeks, by both uni- and cross-modal plasticity mechanisms, in a time-dependent manner. So far, knowledge about the cortical plasticity phenomena in the visual cortex of adult ME mice was mainly based on in situ hybridization data (ISH) for the activity reporter gene zif268 and focused on one discrete anterior-posterior level in the visual cortex. As a first goal in this dissertation, we decided to engineer a software tool to expand this knowledge for the entire visual cortex and with high resolution. This tool was designed towards constructing top view representations of molecular data from a series of brain slices. By matching each individual animal map to a global reference map, created from all animals under study, maps of different conditions can now be compared quantitatively using a customized randomization test with pseudo t statistics. We applied and validated this novel technique to ISH data for the activity reporter gene zif268 from control and ME mice with a survival time of 3 days, 1, 5 and 7 weeks. With this approach, three, formerly unknown, cortical patches with a deviating recovery pattern were identified and described. Additionally, since the created maps represent the visual input of the remaining ipsilateral eye, an area mask of the visual cortex, including 11 areas, could be inferred based on retinotopy. This mask allowed us to designate a region with strong cross-modal plasticity potential as the extrastriate anteromedial area (AM). Additionally, we compared our area map with the most recently published area mask and we were able to suggest relevant adjustments to create the most up to date area mask for mouse cortex currently available, now representing the spatial context of 13 visual areas with high fidelity. As a second objective, and complementary to our ongoing molecular and cellular research, we investigated the physiological implications of ME, after a recovery period of 7 weeks, in adult (P120) mice, onto visual and tactile response properties in area AM, using extracellular multi-electrode electrophysiology. We demonstrated that the upper layers I-IV of area AM increased in visual performance by an accelerated and transient visual response and an increase in spatial acuity. The lower layers V-VI appeared to improve less visually, based on an increase in spatial acuity, but also a drop in temporal resolution and contrast sensitivity. These lower layers of area AM instead increased their responsiveness to whisker stimulation upon ME, by suppressing or activing neurons in area AM more strongly in comparison to control mice. Displaying the whisker responses spatially within area AM further revealed that these responses were aggregated and create a gradient of modulation across the area. By topically projecting the whisker responses onto the visual field, we could show that the upper and lower peripheral visual fields were processing the whisker input differently. Upon ME, this specialization difference thus resulted in a shift from a vertical to a rather nasal-temporal oriented interpretation. As a third research topic, we focused on the physiological implications of previously reported development-related alterations to the dendritic morphology of layer V neurons in the primary visual cortex (V1) of matrix metalloproteinase 3 (MMP3) deficient mice. MMPs in general regulate extracellular matrix modulation in relation to axonal and dendritic outgrowth, and synapse formation and stabilization. By using extracellular multi-array electrophysiology, we were able to demonstrate that MMP3 deficient mice showed an ipsilateral dominated and contralateral delayed visual input in the layers II/III and IV. However, the neuronal output was contralaterally dominated in layers II-V, revealing an aberrant ipsilateral-contralateral input/output balance in V1, possibly through atypical decussating circuitry. The consequences to the visual response properties included a hampered temporal frequency specificity and an increased binocular contrast sensitivity. Spatial and temporal acuity remained unaffected. To conclude, this dissertation increased our understanding about the functional implications of cortical plasticity processes induced by vision loss or aberrant neuronal morphology. Our findings revealed possibilities for new in depth research on the multisensory interplay of different modalities upon sensory loss. We also see merit in creating, in parallel, a better understanding of the behavioral outcome of such plasticity processes. Together, this knowledge will lead to an improvement of the susceptibility of patients for bionic implants as treatment for blindness or deafness.nrpages: 176status: publishe

Brain-wide analysis of parvalbumin, somatostatin and vasointestinal peptide levels in cortical interneurons of sighted and enucleated mice using a newly developed imaging tool

status: publishe

A tool for brain-wide quantitative analysis of molecular data upon projection into a planar view of choice

Several techniques, allowing the reconstruction and visualization of functional, anatomical or molecular information from tissue and organ slices, have been developed over the years. Yet none allow direct comparison without reprocessing the same slices. Alternative methods using publicly available reference maps like the Allen Brain Atlas lack flexibility with respect to age and species. We propose a new approach to reconstruct a segmented region of interest from serial slices by projecting the optical density values representing a given molecular signal to a plane of view of choice, and to generalize the results into a reference map, which is built from the individual maps of all animals under study. Furthermore, to allow quantitative comparison between experimental conditions, a non-parametric pseudo t-test has been implemented. This new mapping tool was applied, optimized and validated making use of an in situ hybridization dataset that represents the spatiotemporal expression changes for the neuronal activity reporter gene zif268, in relation to cortical plasticity induced by monocular enucleation, covering the entire mouse visual cortex. The created top view maps of the mouse brain allow precisely delineating and interpreting 11 extrastriate areas surrounding mouse V1. As such, and because of the opportunity to create a planar projection of choice, these molecular maps can in the future easily be compared with functional or physiological imaging maps created with other techniques such as Ca2+, flavoprotein and optical imaging.status: publishe

Dynamics of spatial frequency tuning in mouse visual cortex

Neuronal spatial frequency tuning in primary visual cortex (V1) substantially changes over time. In both primates and cats, a shift of the neuron's preferred spatial frequency has been observed from low frequencies early in the response to higher frequencies later in the response. In most cases, this shift is accompanied by a decreased tuning bandwidth. Recently, the mouse has gained attention as a suitable animal model to study the basic mechanisms of visual information processing, demonstrating similarities in basic neuronal response properties between rodents and highly visual mammals. Here we report the results of extracellular single-unit recordings in the anesthetized mouse where we analyzed the dynamics of spatial frequency tuning in V1 and the lateromedial area LM within the lateral extrastriate area V2L. We used a reverse-correlation technique to demonstrate that, as in monkeys and cats, the preferred spatial frequency of mouse V1 neurons shifted from low to higher frequencies later in the response. However, this was not correlated with a clear selectivity increase or enhanced suppression of responses to low spatial frequencies. These results suggest that the neuronal connections responsible for the temporal shift in spatial frequency tuning may considerably differ between mice and monkeys.status: publishe

The cross-modal aspect of mouse visual cortex plasticity induced by monocular enucleation is age dependent

Monocular enucleation (ME) drastically affects the contralateral visual cortex, where plasticity phenomena drive specific adaptations to compensate for the unilateral loss of vision. In adult mice, complete reactivation of deprived visual cortex involves an early visually driven recovery followed by multimodal plasticity 3 to 7 weeks post ME (Van Brussel et al. [2011] Cereb. Cortex 21:2133-2146). Here, we specifically investigated the age dependence of the onset and the exact timing of both ME-induced reactivation processes by comparing cortical activity patterns of mice enucleated at postnatal day (P) 45, 90, or 120. A swifter open-eye potentiated reactivation characterized the binocular visual cortex of P45 mice. Nevertheless, even after 7 weeks, the reactivation remained incomplete, especially in the monocular cortex medial to V1. In comparison with P45, emergent cross-modal participation was demonstrated in P90 animals, although robust reactivation similar to enucleated adults (P120) was not achieved yet. Concomitantly, at 7 weeks post ME, somatosensory and auditory cortex shifted from a hypoactive state in P45 to hyperactivity in P120. Thus, we provide evidence for a presensitive period in which gradual recruitment of cross-modal recovery upon long-term ME coincides with the transition from adolescence to adulthood in mice.status: publishe

Dynamics of spatial frequency tuning in mouse visual cortex

status: publishe

Prolonged optogenetic stimulation of the mouse superior colliculus elicits escaping and orienting behaviour

Aims: Electrical and pharmacological stimulation of the superior colliculus (SC) has been described to mediate a variety of behaviours ranging from freezing, escape and orientation. Here, we investigated the effect of prolonged optogenetic stimulation of the SC. Methods: We used the stable step-function opsin (SSFO), a modified ChR2 channel, which stays active for 20-30 minutes. The right SC of C57Bl6J mice was stereotactically injected with an AAV2/7-CaMKII-SSFO vector. Stimulation consisted of a 2s blue light pulse of 50 mW/mm2on day 1, 3 and 5 and a different batch of animals was stimulated with light powers ranging from 0,05 mW/mm2 to 50 mW/mm2. Results: Upon stimulation with the highest light power, all mice displayed strong escape behaviour at first, running around in their cage. After about 30 seconds they quieted down and showed a counter-clockwise turning behaviour for up to 30 minutes. Using lower light power, there was no escape response , leaving only the long-lasting contralateral orientation turning. Conclusions: At high light powers, SSFO-mediated SC stimulation resulted in a short escape response, despite the prolonged nature of the stimulation that is indicated by the long-lasting turning behaviour. These findings suggest that the circuit for escape behaviour might respond mainly to stimulus onset and loses its responsiveness upon prolonged stimulation. Furthermore, as lower light powers only elicited turning behaviour, stimulus size appears to be an important factor in triggering escape but not orientation. In summary, our data indicate differential response properties of the collicular circuits mediating escape and orientation.status: publishe