The Role of GABAergic Inhibition in Ocular Dominance Plasticity

During the last decade, we have gained much insight into the mechanisms that open and close a sensitive period of plasticity in the visual cortex. This brings the hope that novel treatments can be developed for brain injuries requiring renewed plasticity potential and neurodevelopmental brain disorders caused by defective synaptic plasticity. One of the central mechanisms responsible for opening the sensitive period is the maturation of inhibitory innervation. Many molecular and cellular events have been identified that drive this developmental process, including signaling through BDNF and IGF-1, transcriptional control by OTX2, maturation of the extracellular matrix, and GABA-regulated inhibitory synapse formation. The mechanisms through which the development of inhibitory innervation triggers and potentially closes the sensitive period may involve plasticity of inhibitory inputs or permissive regulation of excitatory synapse plasticity. Here, we discuss the current state of knowledge in the field and open questions to be addressed

Cre-Dependent Expression of Multiple Transgenes in Isolated Neurons of the Adult Forebrain

Background: Transgenic mice with mosaic, Golgi-staining-like expression of enhanced green fluorescent protein (EGFP) have been very useful in studying the dynamics of neuronal structure and function. In order to further investigate the molecular events regulating structural plasticity, it would be useful to express multiple proteins in the same sparse neurons, allowing co-expression of functional proteins or co-labeling of subcellular compartments with other fluorescent proteins. However, it has been difficult to obtain reproducible expression in the same subset of neurons for direct comparison of neurons expressing different functional proteins. Principal Findings: Here we describe a Cre-transgenic line that allows reproducible expression of transgenic proteins of choice in a small number of neurons of the adult cortex, hippocampus, striatum, olfactory bulb, subiculum, hypothalamus, superior colliculus and amygdala. We show that using these Cre-transgenic mice, multiple Cre-dependent transgenes can be expressed together in the same isolated neurons. We also describe a Cre-dependent transgenic line expressing a membrane associated EGFP (EGFP-F). Crossed with the Cre-transgenic line, EGFP-F expression starts in the adolescent forebrain, is present in dendrites, dendritic protrusions, axons and boutons and is strong enough for acute or chronic in vivo imaging. Significance: This triple transgenic approach will aid the morphological and functional characterization of neurons in various Cre-dependent transgenic mice

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