Barrel Cortex - Experience-dependent Plasticity

Experience-dependent Plasticity

Experience-dependent plasticity is commonly studied in the barrel cortex by partially depriving it of sensory input, either by lesioning elements of the afferent pathway (e.g. the trigeminal nerve) or by ablating, plucking, or trimming some of the facial whiskers. Only lesioning affects the anatomical structure of the barrels, but innocuous forms of deprivation can induce rapid changes in the cortical map into adulthood, without any corresponding changes in the barrel structures. These two paradigms seem to work by different mechanisms.

Some forms of plasticity in the barrel cortex display a critical period. Plucking whiskers in neonatal rats causes a long-lasting expansion of the representation of the spared whisker in layer 4. However, layer 4 plasticity rapidly diminishes if sensory deprivation begins after day 4 of life (P4) whereas representations in layer 2/3 remain highly plastic into adulthood.

Two cortical processes run alongside each other when barrel cortex is deprived of sensory input from some whiskers to produce representational plasticity. In deprived cortex neuronal responses to spared whiskers are enhanced, and responses to deprived whiskers are weakened. These two processes have different time courses, with the weakening of deprived response preceding the strengthening of spared response, implying that they have different underlying mechanisms. These two effects combine to produce an expansion of the cortical representation of spared whiskers into the representation of adjacent deprived whiskers.

It is likely that several different mechanisms are involved in producing experience-dependent plasticity in a whisker deprivation protocol (adapted from Feldman and Brecht, 2005 ):

1. There is an immediate unmasking effect, where loss of input to a deprived barrel column leads to a loss of inhibitory firing in that column which unmasks horizontal excitatory connections from adjacent spared columns. This does not explain longer-lasting plastic changes as the unmasking would disappear immediately if the deprived input was reinstated (for example by allowing the whisker to regrow).
2. The involvement of LTP- and LTD-like processes is suggested by the observation that plasticity can be compromised by interfering with expression of calmodulin-dependent protein kinase II (CaMKII) or cyclic-AMP response element binding protein (CREB) in transgenic mice. Spike timing rather than frequency may be an important factor. Associative LTP has been demonstrated at layer 4 to layer 2/3 synapses when the layer 4 neuron fires 0-15 ms before the layer 2/3 neuron, and LTD is observed when this timing order is reversed. Such mechanisms could act rapidly to produce plastic changes within hours or days.
3. Sensory deprivation has been demonstrated to cause changes in synaptic dynamics such as EPSP amplitude and frequency. The net effect of these changes is to increase the proportion of synaptic input which layer 2/3 neurons in deprived barrels receive from spared barrels. These observations suggest that other, more specific, mechanisms besides LTP/LTD are at play in experience-dependent plasticity.
4. It seems intuitively likely that structural changes at the level of axons, dendrite branches, and dendrite spines underlie some of the long-term plastic changes in the cortex. Axonal remodelling has been reported in lesion-induced plasticity but not (until now) in experience-dependent plasticity, but a recent study by Cheetham et al. found that whisker trimming produces targeted axonal remodelling in spared cortex. Dendritic branching is important during prenatal and neonatal development, is involved in plasticity induced by lesions, but is not involved in experience-dependent plasticity. In vivo two-photon microscopy reveals that dendritic spines in mouse barrel cortex are highly dynamic and subject to continuous turnover, and may be associated with formation or deletion of synapses. It is likely that spine turnover is necessary but not sufficient to produce experience-dependent plasticity, and other mechanisms such as axonal remodelling are also needed to explain features such as savings from prior experience.