A primary sensory cortical interareal feedforward inhibitory circuit for tacto-visual integration.

Tactile sensation and vision are often both utilized for the exploration of objects that are within reach though it is not known whether or how these two distinct sensory systems combine such information. Here in mice, we used a combination of stereo photogrammetry for 3D reconstruction of the whisker array, brain-wide anatomical tracing and functional connectivity analysis to explore the possibility of tacto-visual convergence in sensory space and within the circuitry of the primary visual cortex (VISp). Strikingly, we find that stimulation of the contralateral whisker array suppresses visually evoked activity in a tacto-visual sub-region of VISp whose visual space representation closely overlaps with the whisker search space. This suppression is mediated by local fast-spiking interneurons that receive a direct cortico-cortical input predominantly from layer 6 neurons located in the posterior primary somatosensory barrel cortex (SSp-bfd). These data demonstrate functional convergence within and between two primary sensory cortical areas for multisensory object detection and recognition.

Social hierarchy regulates ocular dominance plasticity in adult male mice.

We here show that social rank, as assessed by competition for a running wheel, influences ocular dominance plasticity in adult male mice. Dominant animals showed a clear ocular dominance shift after 4 days of MD, whereas their submissive cagemates did not. NMDA receptor activation, reduced GABA inhibition, and serotonin transmission were necessary for this plasticity, but not sufficient to explain the difference between dominant and submissive animals. In contrast, prefrontal dopamine concentration was higher in dominant than submissive mice, and systemic manipulation of dopamine transmission bidirectionally changed ocular dominance plasticity. Thus, we could show that a social hierarchical relationship influences ocular dominance plasticity in the visual cortex via higher-order cortices, most likely the medial prefrontal cortex. Further studies will be needed to elucidate the precise mechanisms by which this regulation takes place.

Visual deprivation independent shift of ocular dominance induced by cross-modal plasticity.

There is convincing evidence that the deprivation of one sense can lead to adaptive neuronal changes in spared primary sensory cortices. However, the repercussions of late-onset sensory deprivations on functionality of the remaining sensory cortices are poorly understood. Using repeated intrinsic signal imaging we investigated the effects of whisker or auditory deprivation (WD or AD, respectively) on responsiveness of the binocular primary visual cortex (V1) in fully adult mice. The binocular zone of mice is innervated by both eyes, with the contralateral eye always dominating V1 input over ipsilateral eye input, the normal ocular dominance (OD) ratio. Strikingly, we found that 3 days of WD or AD induced a transient shift of OD, which was mediated by a potentiation of V1 input through the ipsilateral eye. This cross-modal effect was accompanied by strengthening of layer 4 synapses in V1, required visual experience through the ipsilateral eye and was mediated by an increase of the excitation/inhibition ratio in V1. Finally, we demonstrate that both WD and AD induced a long-lasting improvement of visual performance. Our data provide evidence that the deprivation of a non-visual sensory modality cross-modally induces experience dependent V1 plasticity and improves visual behavior, even in adult mice.

Cross-modal Restoration of Juvenile-like Ocular Dominance Plasticity after Increasing GABAergic Inhibition.

In juvenile and young adult mice monocular deprivation (MD) shifts the ocular dominance (OD) of binocular neurons in the primary visual cortex (V1) away from the deprived eye. However, OD plasticity is completely absent in mice older than 110 days, but can be reactivated by treatments which decrease GABA levels in V1. Typically, these OD shifts can be prevented by increasing GABAergic transmission with diazepam. We could recently demonstrate that both bilateral whisker and auditory deprivation (WD, AD), can also restore OD plasticity in mice older than 110 days, since MD for 7 days in WD mice caused a potentiation of V1 input through the ipsilateral (open) eye, the characteristic feature of OD plasticity of "young adult" mice. Here we examined whether WD for 7 days also decreases GABA levels. For this, we performed post mortem HPLC analysis of V1 tissue. Indeed, we found that WD significantly decreased GABA levels in V1. Surprisingly, enhancing GABAergic inhibition by diazepam did not abolish OD shifts in WD mice, as revealed by repeated intrinsic signal imaging. On the contrary, this treatment led to a depression of V1 input through the previously closed contralateral eye, the characteristic signature of OD plasticity in juvenile mice during the critical period. Interestingly, the same result was obtained after AD. Taken together, these results suggest that cross-modally restored OD plasticity does not only depend on reduction of GABA levels in V1, but also requires other, so far unknown mechanisms.

Cross-modal restoration of ocular dominance plasticity in adult mice.

The temporal closure of one eye in juvenile and young adult mice induces a shift of the ocular dominance (OD) of neurons in the binocular visual cortex. However, OD plasticity typically declines with age and is completely absent in matured mice beyond postnatal day (PD) 110. As it has been shown that the deprivation of one sensory input can induce neuronal alterations in non-deprived sensory cortices, we here investigated whether cross-modal interactions have the potential to reinstall OD plasticity in matured mice. Strikingly, using intrinsic signal imaging we could demonstrate that both whisker deprivation and auditory deprivation for only one week reinstated OD plasticity in fully adult mice. These OD shifts were always mediated by an increase of V1 responsiveness to visual stimulation of the open eye, a characteristic feature of OD plasticity normally only found in young adult mice. Moreover, systemic administration of the competitive NMDA receptor antagonist CPP completely abolished cross-modally induced OD plasticity. Taken together, we demonstrate here for the first time that the deprivation of non-visual senses has the potential to rejuvenate the adult visual cortex.

Cross-modal refinement of visual performance after brief somatosensory deprivation in adult mice.

It is well established that the congenital lack of one sensory modality enhances functionality in the spared senses. However, whether a late onset deprivation of one sense leads to such alterations is largely unknown. Here, we investigated whether a somatosensory deprivation induced by bilateral whisker removal affects visual acuity and contrast sensitivity in fully adult mice. Using the visual cortex-dependent visual water task, we found that a brief somatosensory deprivation markedly improved behavioral visual acuity and contrast sensitivity by about 40%. Determining these attributes of vision using periodic optical imaging of intrinsic signals in the same mice revealed that visual cortex responses elicited by weak visual stimuli were massively increased after somatosensory deprivation. Strikingly, comparison of visual acuity and contrast sensitivity values determined by the visual water task and intrinsic signal imaging revealed that these measurements were almost identical, even at the level of individual animals. In summary, our results suggest that a brief manipulation of somatosensory experience profoundly boosts visual cortex-dependent vision in adults.

Embryonic interneurons from the medial, but not the caudal ganglionic eminence trigger ocular dominance plasticity in adult mice.

The maturation of cortical inhibition provided by parvalbumin-containing basket cells derived from the medial ganglionic eminence (MGE) is a key event in starting the enhanced visual cortical plasticity during the critical period. Although it is generally assumed that a further increase in inhibition closes the critical period again, it was recently shown that embryonic interneurons derived from the MGE can induce an additional, artificial critical period when injected into the visual cortex of young mice. It has, however, remained open whether this effect was indeed specific for MGE-derived cells, and whether critical period-like plasticity could also be induced in fully adult animals. To clarify these issues, we injected explants from either the MGE or the caudal ganglionic eminence (CGE) into the visual cortices of fully adult mice, and performed monocular deprivation 33 days later for 4 days. Animals implanted with MGE cells, but not with CGE cells, showed marked ocular dominance plasticity. Immunohistochemistry confirmed that the injected cells from both sources migrated far in the host cortex, that most developed into neurons producing GABA, and that only cells from the MGE expressed parvalbumin. Thus, our results confirm that the plasticity-inducing effect of embryonic interneurons is specific for cells from the MGE, and is independent of the host animal's age.