Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC) in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28) or P58 on the density of parvalbumin (PV), calbindin (CB), and calretinin (CR) neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6). Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

One of the most significant effects of neural plasticity manifests in the case of sensory deprivation when cortical areas that were originally specialized for the functions of the deprived sense take over the processing of another modality. Vision and audition represent two important senses needed to navigate through space and time. Therefore, the current systematic review discusses the cross-modal behavioral and neural consequences of deafness and blindness by focusing on spatial and temporal processing abilities, respectively. In addition, movement processing is evaluated as compiling both spatial and temporal information. We examine whether the sense that is not primarily affected changes in its own properties or in the properties of the deprived modality (i.e., temporal processing as the main specialization of audition and spatial processing as the main specialization of vision). References to the metamodal organization, supramodal functioning, and the revised neural recycling theory are made to address global brain organization and plasticity principles. Generally, according to the reviewed studies, behavioral performance is enhanced in those aspects for which both the deprived and the overtaking senses provide adequate processing resources. Furthermore, the behavioral enhancements observed in the overtaking sense (i.e., vision in the case of deafness and audition in the case of blindness) are clearly limited by the processing resources of the overtaking modality. Thus, the brain regions that were previously recruited during the behavioral performance of the deprived sense now support a similar behavioral performance for the overtaking sense. This finding suggests a more input-unspecific and processing principle-based organization of the brain. Finally, we highlight the importance of controlling for and stating factors that might impact neural plasticity and the need for further research into visual temporal processing in deaf subjects.

Visual stimuli are known to activate the auditory cortex of deaf people, presenting evidence of cross-modal plasticity. However, the mechanisms underlying such plasticity are poorly understood. In this functional MRI study, we presented two types of visual stimuli, language stimuli (words, sign language, and lip-reading) and a general stimulus (checkerboard) to investigate neural reorganization in the superior temporal cortex (STC) of deaf subjects and hearing controls. We found that only in the deaf subjects, all visual stimuli activated the STC. The cross-modal activation induced by the checkerboard was mainly due to a sensory component via a feed-forward pathway from the thalamus and primary visual cortex, positively correlated with duration of deafness, indicating a consequence of pure sensory deprivation. In contrast, the STC activity evoked by language stimuli was functionally connected to both the visual cortex and the frontotemporal areas, which were highly correlated with the learning of sign language, suggesting a strong language component via a possible feedback modulation. While the sensory component exhibited specificity to features of a visual stimulus (e.g., selective to the form of words, bodies, or faces) and the language (semantic) component appeared to recruit a common frontotemporal neural network, the two components converged to the STC and caused plasticity with different multivoxel activity patterns. In summary, the present study showed plausible neural pathways for auditory reorganization and correlations of activations of the reorganized cortical areas with developmental factors and provided unique evidence towards the understanding of neural circuits involved in cross-modal plasticity.

Postnatal sensory experience plays a significant role in the maturation and synaptic stabilization of sensory cortices, such as the primary auditory cortex (A1). Here, we examined the effects of patterned sound deprivation (by rearing in continuous white noise, WN) during early postnatal life on short- and long-term plasticity of adult male rats using an in vivo preparation (urethane anesthesia). Relative to age-matched control animals reared under unaltered sound conditions, rats raised in WN (from postnatal day 5 to 50-60) showed greater levels of long-term potentiation (LTP) of field potentials in A1 induced by theta-burst stimulation (TBS) of the medial geniculate nucleus (MGN). In contrast, analyses of short-term plasticity using paired-pulse stimulation (interstimulus intervals of 25-1000 ms) did not reveal any significant effects of WN rearing. However, LTP induction resulted in a significant enhancement of paired-pulse depression (PPD) for both rearing conditions. We conclude that patterned sound deprivation during early postnatal life results in the maintenance of heightened, juvenile-like long-term plasticity (LTP) into adulthood. Further, the enhanced PPD following LTP induction provides novel evidence that presynaptic mechanisms contribute to thalamocortical LTP in A1 under in vivo conditions.

Npas4 has recently been identified as an important factor in brain plasticity, particularly in mechanisms of inhibitory control. Little is known about Npas4 expression in terms of cortical plasticity. In the present study expressions of Npas4 and the archetypal immediate early gene (IEG) c-Fos were investigated in the barrel cortex of mice after sensory deprivation (sparing one row of whiskers for 7 days) or sensory conditioning (pairing stimulation of one row of whiskers with aversive stimulus). Laser microdissection of individual barrel rows allowed for analysis of IEGs expression precisely in deprived and nondeprived barrels (in deprivation study) or stimulated and nonstimulated barrels (in conditioning study). Cortex activation by sensory conditioning was found to upregulate the expression of both Npas4 and c-Fos. Reorganization of cortical circuits triggered by removal of selected rows of whiskers strongly affected c-Fos but not Npas4 expression. We hypothesize that increased inhibitory synaptogenesis observed previously after conditioning may be mediated by Npas4 expression.

Loss of sensory input from peripheral organ damage, sensory deprivation, or brain damage can result in adaptive or maladaptive changes in sensory cortex. In previous research, we found that auditory cortical tuning and tonotopy were impaired by cross-modal invasion of visual inputs. Sensory deprivation is typically associated with a loss of inhibition. To determine whether inhibitory plasticity is responsible for this process, we measured pre- and postsynaptic changes in inhibitory connectivity in ferret auditory cortex (AC) after cross-modal plasticity. We found that blocking GABAA receptors increased responsiveness and broadened sound frequency tuning in the cross-modal group more than in the normal group. Furthermore, expression levels of glutamic acid decarboxylase (GAD) protein were increased in the cross-modal group. We also found that blocking inhibition unmasked visual responses of some auditory neurons in cross-modal AC. Overall, our data suggest a role for increased inhibition in reducing the effectiveness of the abnormal visual inputs and argue that decreased inhibition is not responsible for compromised auditory cortical function after cross-modal invasion. Our findings imply that inhibitory plasticity may play a role in reorganizing sensory cortex after cross-modal invasion, suggesting clinical strategies for recovery after brain injury or sensory deprivation.

Experience modifies synaptic connectivity through processes that involve dendritic spine rearrangements in neuronal circuits. Although cAMP response element binding protein (CREB) has a key function in spines changes, its role in activity-dependent rearrangements in brain regions of rodents interacting with the surrounding environment has received little attention so far. Here we studied the effects of vibrissae trimming, a widely used model of sensory deprivation-induced cortical plasticity, on processes associated with dendritic spine rearrangements in the barrel cortex of a transgenic mouse model of CREB downregulation (mCREB mice). We found that sensory deprivation through prolonged whisker trimming leads to an increased number of thin spines in the layer V of related barrel cortex (Contra) in wild type but not mCREB mice. In the barrel field controlling spared whiskers (Ipsi), the same trimming protocol results in a CREB-dependent enlargement of dendritic spines. Last, we demonstrated that CREB regulates structural rearrangements of synapses that associate with dynamic changes of dendritic spines. Our findings suggest that CREB plays a key role in dendritic spine dynamics and synaptic circuits rearrangements that account for new brain connectivity in response to changes in the environment.

The nervous system is highly sensitive to experience during early postnatal life, but this phase of heightened plasticity decreases with age. Recent studies have demonstrated that developmental-like plasticity can be reactivated in the visual cortex of adult animals through environmental or pharmacological manipulations. These findings provide a unique opportunity to study the cellular and molecular mechanisms of adult plasticity. Here we used the monocular deprivation paradigm to investigate large-scale gene expression patterns underlying the reinstatement of plasticity produced by fluoxetine in the adult rat visual cortex. We found changes, confirmed with RT-PCRs, in gene expression in different biological themes, such as chromatin structure remodelling, transcription factors, molecules involved in synaptic plasticity, extracellular matrix, and excitatory and inhibitory neurotransmission. Our findings reveal a key role for several molecules such as the metalloproteases Mmp2 and Mmp9 or the glycoprotein Reelin and open up new insights into the mechanisms underlying the reopening of the critical periods in the adult brain.