Scatter measures the quality of retinotopy and values decrease in development.

<p>(A) The visual cortex was imaged while the mouse watched a white bar drift across the stimulus screen. The evoked intrinsic signal was optically imaged by measuring the reflectance of 700 nm light off of the brain. Using Fourier analysis, magnitude and phase response maps were computed from the image data and used to generate a scatter map. (B) Scatter is measured as the difference, in degrees of elevation in visual space, between a pixel and its neighbors in a 5×5 box. Pixels from two different ipsilateral eye retinotopic maps (from a P17 mouse at left, and a P21 mouse at right) have the same receptive field elevation angle, but different scatter values.</p

Map scatter and response magnitude are significantly independent measures and a threshold used in analysis does not affect the results of present study.

<p>(A) For six animals, map scatter measurements are plotted against response magnitude. Each marker is a different time point in the color-coded period. The Pearson's R² correlation measurement for each animal is shown above each scatter plot. There was no systematic, strong correlation observed between response magnitude and map scatter, thus indicating a significant amount of independence in these two measures. (B) Magnitude maps were thresholded at a level equal to 60% of the maximum in order to define a region of interest for analysis of scatter maps. The results of the current study have been recomputed for various alternative threshold levels. Example scatter maps with the indicated threshold applied are shown above a plot of reduction in map scatter after ME versus threshold used in the analysis.</p

Chronic <i>in vivo</i> imaging in adult mice reveals improvements in ipsilateral retinotopic maps after monocular enucleation (ME) of the contralateral eye.

<p>(A, upper panel) Example scatter maps from the same animal show a reduction in scatter values after ME. (A, lower panel) Cumulative histogram of the two maps shown in the upper panel shows a leftward shift after ME, indicating more low scatter pixels in the retinotopic map. (B) Group data show that scatter values do not decrease immediately, but decrease 30% during the third week after ME (late post ME). (C, upper panel) Outlines of responsive cortex for the three pre ME time points and the three late post ME time points in the same animal overlap each other indicating little change in the area or location of responsive cortex. The outlines were aligned using vascular images. (C, lower panel) Change in scatter is plotted versus the change in area of responsive cortex showing that scatter values consistently decrease (points lie below the horizontal line) while no trend in area changes is observed (points evenly distributed on either side of the vertical line). Data from the example animal is colored black. (D) Group data show that the area of responsive cortex does not change after ME. (E, upper panel) Example magnitude maps show responsiveness before ME and during the third week after ME (late post ME). (E, lower panel) Change in scatter is plotted versus the change in maximum response magnitude showing that scatter values consistently decrease (points lie below the horizontal line) while maximum response magnitude consistently increases (points lie to the right of the vertical line). Data from the example animal is colored black. (F) Group data show that maximum response magnitude increases 30% during the third week after ME (late post ME). Reported p-values were computed using a paired, two-tailed t-test.</p

Fast-spiking interneurons have an initial orientation bias that is lost with vision.

We found that in mice, following eye opening, fast-spiking, parvalbumin-positive GABAergic interneurons had well-defined orientation tuning preferences and that subsequent visual experience broadened this tuning. Broad inhibitory tuning was not required for the developmental sharpening of excitatory tuning but did precede binocular matching of excitatory orientation tuning. We propose that experience-dependent broadening of inhibition is a candidate for initiating the critical period of excitatory binocular plasticity in developing visual cortex.</p

A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex.

<p>Early sensory experience instructs the maturation of neural circuitry in the cortex. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.</p

Loss of Cntnap2 decreases specifically stabilization of new spines.

<p><b>a.</b> From left to right: Chronic imaging through a cranial window of L5 pyramidal neuron. The 3 images on the right show the dynamics of spines on a dendrite segment followed for 11 days. <b>b-e. Top</b> a spine (red) on a dendrite (black) at the indicated imaging days. <b>Left plots</b> analysis per mouse (n = 10 Cntnap2-/- mice, n = 8 WT mice). <b>Right plots</b> analysis per cell (n = 23 Cntnap2-/- neurons, n = 18 WT neurons). <b>b.</b> The fraction of spines lost during 4 days. Note the significant increase in spine loss in Cntnap2-/- mice. <b>c.</b> The fraction of spines gain. Note the absence of a significant difference between WT and Cntnap2-/- animals. <b>d.</b> The fraction of maintained spines out of the spines which were stable during the first 4 days. Note the absence of a significant difference between WT and Cntnap2-/- animals. <b>e.</b> The fraction of stable spines out of the spines gained in the first 4 days. Note the significant decrease in Cntnap2-/- mice. (Error bars indicate standard error (SEM), NS non significant; * P<0.05; **P<0.01; t-Tests).</p

Loss of Cntnap2-/- decreases spine density.

<p><b>a.</b> Low magnification images of dendrites and spines in WT mouse (<b>left)</b>, and in Cntnap2-/- mouse <b>(right)</b>. <b>b.</b> Quantification of spine-density. <b>Top plot</b> analysis per mouse (n = 10 Cntnap2-/- mice, n = 8 WT mice). <b>Bottom plot</b> analysis per cell (n = 23 Cntnap2-/- neurons, n = 18 WT neurons). Note the significant decrease in spine density in Cntnap2-/- mice (right) relative to WT (left).(Error bars indicate standard error (SEM), * P<0.05; **P<0.01; t-Test).</p

Encoding and storage of spatial information in the retrosplenial cortex.

<p>The retrosplenial cortex (RSC) is part of a network of interconnected cortical, hippocampal, and thalamic structures harboring spatially modulated neurons. The RSC contains head direction cells and connects to the parahippocampal region and anterior thalamus. Manipulations of the RSC can affect spatial and contextual tasks. A considerable amount of evidence implicates the role of the RSC in spatial navigation, but it is unclear whether this structure actually encodes or stores spatial information. We used a transgenic mouse in which the expression of green fluorescent protein was under the control of the immediate early gene c-fos promoter as well as time-lapse two-photon in vivo imaging to monitor neuronal activation triggered by spatial learning in the Morris water maze. We uncovered a repetitive pattern of cell activation in the RSC consistent with the hypothesis that during spatial learning an experience-dependent memory trace is formed in this structure. In support of this hypothesis, we also report three other observations. First, temporary RSC inactivation disrupts performance in a spatial learning task. Second, we show that overexpressing the transcription factor CREB in the RSC with a viral vector, a manipulation known to enhance memory consolidation in other circuits, results in spatial memory enhancements. Third, silencing the viral CREB-expressing neurons with the allatostatin system occludes the spatial memory enhancement. Taken together, these results indicate that the retrosplenial cortex engages in the formation and storage of memory traces for spatial information.</p