A Small Motor Cortex Lesion Abolished Ocular Dominance Plasticity in the Adult Mouse Primary Visual Cortex and Impaired Experience-Dependent Visual Improvements.

It was previously shown that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and sensory learning in the adult mouse visual system: While 3-month-old control mice continued to show ocular dominance (OD) plasticity in their primary visual cortex (V1) after monocular deprivation (MD), age-matched mice with a small photothrombotically induced (PT) stroke lesion in S1, positioned at least 1 mm anterior to the anterior border of V1, no longer expressed OD-plasticity. In addition, in the S1-lesioned mice, neither the experience-dependent increase of the spatial frequency threshold ("visual acuity") nor of the contrast threshold ("contrast sensitivity") of the optomotor reflex through the open eye was present. To assess whether these plasticity impairments can also occur if a lesion is placed more distant from V1, we tested the effect of a PT-lesion in the secondary motor cortex (M2). We observed that mice with a small M2-lesion restricted to the superficial cortical layers no longer expressed an OD-shift towards the open eye after 7 days of MD in V1 of the lesioned hemisphere. Consistent with previous findings about the consequences of an S1-lesion, OD-plasticity in V1 of the nonlesioned hemisphere of the M2-lesioned mice was still present. In addition, the experience-dependent improvements of both visual acuity and contrast sensitivity of the open eye were severely reduced. In contrast, sham-lesioned mice displayed both an OD-shift and improvements of visual capabilities of their open eye. To summarize, our data indicate that even a very small lesion restricted to the superficial cortical layers and more than 3mm anterior to the anterior border of V1 compromised V1-plasticity and impaired learning-induced visual improvements in adult mice. Thus both plasticity phenomena cannot only depend on modality-specific and local nerve cell networks but are clearly influenced by long-range interactions even from distant brain regions

Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice.

Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of cortical plasticity, namely the long-range influence on V1-plasticity after an S1-lesion

Assessment of particle-tracking models for dispersed particle-laden flows implemented in OpenFOAM and ANSYS FLUENT

In the present study two benchmark problems for turbulent dispersed particle-laden flow are investigated with computational fluid dynamics (CFD). How the CFD programs OpenFOAM and ANSYS FLUENT model these flows is tested and compared. The numerical results obtained with Lagrangian–Eulerian (LE) point-particle (PP) models for Reynolds-averaged Navier–Stokes (RANS) simulations of the fluid flow in steady state and transient modes are compared with the experimental data available in the literature. The effect of the dispersion model on the particle motion is investigated in particular, as well as the order of coupling between the continuous carrier phase and the dispersed phase. First, a backward-facing step (BFS) case is validated. As a second case, the confined bluff body (CBB) is used. The simulated fluid flows correspond well with the experimental data for both test cases. The results for the dispersed solid phase reveal a good accordance between the simulation results and the experiments. It seems that particle dispersion is slightly under-predicted when ANSYS FLUENT is used, whereas the applied solver in OpenFOAM overestimates the dispersion somewhat. Only minor differences between the coupling schemes are detected due to the low volume fractions and mass loadings that are investigated. In the BFS test case the importance of the spatial dimension of the numerical model is demonstrated. Even if it is reasonable to assume a two-dimensional fluid flow structure, it is crucial to simulate the turbulent particle-laden flow with a three-dimensional model since the turbulent dispersion of the particles is three-dimensional

Localization and size of the cortical stroke.

<p>(A) Scheme of the average lesion location (red dotted circle/line) and size in the left motor cortex (M2) in respect to the primary visual cortex (V1) of a mouse brain. (B) Nissl-stained frontal section through a representative lesion, WM-white matter. Scale bar: 500μm.</p

A cortical lesion in M2 impairs OD-plasticity in the visual cortex of the lesioned hemisphere.

<p>Optically recorded activity maps of the contralateral (contra) and ipsilateral (ipsi) eye in the binocular region of mouse primary visual cortex (V1) in sham-treated control mice (A, B) and in mice with a PT-lesion in M2 of the recorded hemisphere (C, D). Activity maps without MD are illustrated in the left column (A, C), maps after MD in the right column (B, D). Gray-scale coded response-magnitude maps and their quantification (top), and color-coded phase and polar maps of retinotopy (middle, bottom) are illustrated. The magnitude of the optical responses is illustrated as fractional change in reflection x10^-4. For each experiment, the histogram of OD-scores (upper right), the OD-index (ODI), and the corresponding 2D OD-maps (ODI values are color-coded: red represents positive, blue negative values) are included. Note that without MD, activity patches evoked by stimulation of the contralateral eye were consistently darker than those after stimulation of the ipsilateral eye, 2D OD-maps display warm colors, and the average ODI is positive, indicating contralateral dominance (A, C). In contrast, MD for 7 days in control- (B) but <i>not</i> PT-animals (D) induced an OD-shift toward the open (ipsilateral) eye: the activity map of the ipsilateral eye was even darker than after contralateral (deprived) eye stimulation (black circle indicates MD eye), the histogram of OD-scores shifted to the left (blue arrow in B), the ODI was negative, and colder colors prevailed in the OD-map. In contrast, in PT-animals with MD (D), activity maps of the deprived (contra) eye remained darker than those of the open eye, the histogram of OD-scores and the average ODI were essentially unchanged and warm colors still prevailed in the OD-map.</p

Quantification of the OD-indices and V1-activation.

<p>(A, B) Optically imaged OD-indices in sham-treated (control, blue) animals and after PT in M2 (red) without and with 7 days of MD of the right eye. Symbols represent ODI-values of individuals, means are marked by horizontal lines. (C, D) V1-activation elicited by stimulation of the contralateral (C) or ipsilateral (I) eye in control animals and after MD (black circle indicates MD eye). (A) In control mice, MD induced an OD-shift towards the open eye. In contrast, PT-mice did not show a significant OD-shift in the lesioned, left hemisphere. (B) In contrast, in the nonlesioned, right hemisphere, MD induced an OD-shift in PT-mice, as in control animals. (C, D) V1-activation after stimulation of the contra- and ipsilateral eye before and after MD in both control and PT-lesioned mice.</p

The M2-lesion severely impaired improvements of visual capabilities of the open eye after MD.

<p>Spatial frequency selectivity of the optokinetic response of the open eye in cycles per degree (cyc/deg) plotted against days (A) and contrast sensitivity at 6 different spatial frequencies (B) in control and PT-mice without and with MD (+MD). In both, control and PT-mice, values of the nondeprived (open) eye increased compared to mice without MD. However, the increase in PT-mice was only about 50% of the improvement of control mice.</p

The experience-enabled enhancement of the optomotor reflex of the open eye after monocular deprivation (MD) was compromised in both PT-lesioned PSD-95 WT and PSD-95 KO mice.

<p>In contrast, enhancements of spatial vision were present in nonlesioned PSD-95 WT and PSD-95 KO mice. (A, B) Spatial frequency threshold of the optomotor response of the open eye in cycles per degree (cyc/deg) plotted against days after MD. After 7 days of MD, nonlesioned PSD-95 KO mice (A) as well as sham-treated control mice (B; data from Greifzu et al., 2011) showed a significant increase in the spatial frequency threshold of the optomotor reflex of the open eye. This experience-enabled increase was abolished by a PT in S1 (A, B). (C-F) Contrast sensitivity thresholds of the optomotor reflex of the open eye at 6 different spatial frequencies before (day 0) and 7 days after MD. For both nonlesioned PSD-95 KO (C) and PSD-95 WT mice (D), there was an increase in contrast sensitivity after 7 days of MD. After PT, this experience-enabled increase was absent in both groups (E, F).</p

Location of the photothrombotically induced cortical stroke lesion in a PSD-95 KO mouse in S1 (PT, red dashed line).

<p>(A) Top view of a representative mouse brain illustrating the lesion location in S1, on average 1 mm anterior to the anterior border of the primary visual cortex (V1, blue dashed line). (B) Nissl-stained frontal section through the lesion (same animal as in A). (C) Higher magnification composite image of the superficial vascular pattern of the brain and the superimposed optically recorded retinotopic map of the binocular part of V1 of a PSD-95 KO mouse in which the PT-lesion (L) was very close to V1; nevertheless, OD-plasticity was present in this animal (average ODI = 0.00). Scale bar all, 1 mm.</p