During development, cortical plasticity is associated with the rearrangement of excitatory connections. While these connections become more stable with age, plasticity can still be induced in the adult cortex. Here we provide evidence that structural plasticity of inhibitory synapses onto pyramidal neurons is a major component of plasticity in the adult neocortex. In vivo two-photon imaging was used to monitor the formation and elimination of fluorescently labeled inhibitory structures on pyramidal neurons. We find that ocular dominance plasticity in the adult visual cortex is associated with rapid inhibitory synapse loss, especially of those present on dendritic spines. This occurs not only with monocular deprivation but also with subsequent restoration of binocular vision. We propose that in the adult visual cortex the experience-induced loss of inhibition may effectively strengthen specific visual inputs with limited need for rearranging the excitatory circuitry.

During critical periods of development, experience shapes cortical circuits, resulting in the acquisition of functions used throughout life. The classic example of critical-period plasticity is ocular dominance (OD) plasticity, which optimizes binocular vision but can reduce the responsiveness of the primary visual cortex (V1) to an eye providing low-grade visual input. The onset of the critical period of OD plasticity involves the maturation of inhibitory synapses within V1, specifically those containing the GABA receptor α1 subunit. Here we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus (dLGN) also undergo OD plasticity. This process depends on thalamic α1-containing synapses and is required for consolidation of the OD shift in V1 during long-term deprivation. Our findings demonstrate that thalamic inhibitory circuits play a central role in the regulation of the critical period. This has far-reaching consequences for the interpretation of studies investigating the molecular and cellular mechanisms regulating critical periods of brain development.

BackgroundInhibitory 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 Ca2+ 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 FindingsWe 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/SignificanceWe show that in the adult visual cortex Syt2 is only found in inhibitory, VGAT positive boutons. Practically all Syt2 positive boutons also contain PV and vice versa. During development, Syt2 expression can be detected in synaptic boutons prior to PV and in contrast to PV expression, Syt2 is not down-regulated by dark-rearing. These properties of Syt2 make it an excellent marker for analyzing the development and plasticity of perisomatic inhibitory innervations onto both excitatory and inhibitory neurons in the visual cortex.