Amblyopia: The Thalamus Is a No-Go Area for Visual Acuity

When one eye does not function well during development, the visual cortex becomes less responsive to it and visual acuity declines. New research suggests that reduced response strength and deteriorating acuity occur in separate circuits. When one eye does not function well during development, the visual cortex becomes less responsive to it and visual acuity declines. New research suggests that reduced response strength and deteriorating acuity occur in separate circuits

Inhibitory interneurons in visual cortical plasticity

For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, it is essential that these critical periods end after which learning becomes more conditional and active interaction with the environment becomes more important. How these age-dependent forms of plasticity are regulated has been studied extensively in the primary visual cortex. This has revealed that inhibitory innervation plays a crucial role and that a temporary decrease in inhibition is essential for plasticity to take place. Here, we discuss how different interneuron subsets regulate plasticity during different stages of cortical maturation. We propose a theory in which different interneuron subsets select the sources of neuronal input that undergo plasticity

Synaptotagmin-2 Is a Reliable Marker for Parvalbumin Positive Inhibitory Boutons in the Mouse Visual Cortex

Background: Inhibitory innervation by parvalbumin (PV) expressing interneurons has been implicated in the onset of the sensitive period of visual plasticity. Immunohistochemical analysis of the development and plasticity of these inhibitory inputs is difficult because PV expression is low in young animals and strongly influenced by neuronal activity. Moreover, the synaptic boutons that PV neurons form onto each other cannot be distinguished from the innervated cell bodies by immunostaining for this protein because it is present throughout the cells. These problems call for the availability of a synaptic, activity-independent marker for PV+ inhibitory boutons that is expressed before sensitive period onset. We investigated whether synaptotagmin-2 (Syt2) fulfills these properties in the visual cortex. Syt2 is a synaptic vesicle protein involved in fast Ca 2+ dependent neurotransmitter release. Its mRNA expression follows a pattern similar to that of PV throughout the brain and is present in 30–40 % of hippocampal PV expressing basket cells. Up to now, no quantitative analyses of Syt2 expression in the visual cortex have been carried out. Methodology/Principal Findings: We used immunohistochemistry to analyze colocalization of Syt2 with multiple interneuron markers including vesicular GABA transporter VGAT, calbindin, calretinin, somatostatin and PV in the primary visual cortex of mice during development and after dark-rearing. Conclusions/Significance: We show that in the adult visual cortex Syt2 is only found in inhibitory, VGAT positive boutons

Syt2 in L2-3 is expressed in PV positive boutons.

<p>(A–C, arrowhead) Syt2 almost always colocalizes with VGAT in L2-3 of the visual cortex. The arrow indicates a VGAT positive bouton without Syt2 expression. (D–I) Syt2 puncta (arrowhead) are not calretinin (CR, arrow) or somatostatin (SOM, arrow) positive. (J–L) Syt2 shows strong co-expression with PV (arrowheads). A–C & G–I n = 3; D–F & J–L n = 4. Scale bars 10 µm.</p

Syt2 in L2-3 and L5 is not expressed in VGLUT1&2 positive boutons.

<p>(A–F) Syt2 puncta (arrowheads) in L2-3 and L5 are not VGLUT1 positive. Arrows indicate VGLUT1 boutons. VGLUT1 and Syt2 show an alternating perisomatic localization (F). Similarly VGLUT2 boutons, indicated with arrows do not show expression of Syt2. Syt2 puncta indicated with arrowheads (G–L). A–L n = 3. Scale bars 10 µm.</p

Scatter plot pixel analyses of Syt2 colocalization with cell type specific markers in various cortical areas.

<p>(A) Example images of neurons with perisomatic punctate innervation from different areas of the cortex. Adjacent are scatter plots for the same images showing distribution of fluorescence intensities for Syt2 (vertical green channel) and PV (horizontal red channel). As a negative control for colocalization (B) shows examples of Syt2 positive innervations with VGLUT2 or CR. Adjacent are scatter plots showing distribution of fluorescence intensities for Syt2 (vertical green channel) and VGLUT2 or CR (horizontal red channel). (C) The average Manders' coefficients of all the scatter plots. Coefficient values in different cortical areas are similar to V1 for colocalization of Syt2 and PV, and differ strongly from non-colocalization values for Syt2 with VGLUT2 or CR (n = 8; n = 7&8). M1, primary motor cortex (n = 6&9); S1, primary somatosensory cortex (n = 7&10); S1BF, barrel field cortex (n = 11&11); Au1, auditory cortex (n = 4&9). Data in C are given in mean coefficients ± SEM. Scale bar 10 µm.</p