The cellular mechanisms of cortical map reorganisation in primary sensory cortex. (360G-Wellcome-061135_Z_00_C)

A large part of the neocortex is given over to topographic representations of sensory inputs and motor outputs. Many of these maps express experience-dependent plasticity in adulthood. This is of great neurological interest because cortical reorganisation probably contributes to recovery from brain damage. Harnessing experience-dependent plasticity potentially offers therapeutic benefits. However, the simple strategy of maximising plasticity will not work because excess or aberrant reorganisation may cause disease. Realising any therapeutic gain will, therefore, require an understanding of the cellular mechanisms that drive cortical map reorganisation. The sensory input from rat whiskers to primary somatosensory cortex provides an ideal model system to study cortical map plasticity because brief periods of whisker trimming results in reorganisation of the corresponding cortical map. I will investigate the underlying cellular mechanisms level by preparing in vitro brain slices of primary somatosensory cortex that cut across the whisker barrel rows. My general strategy will be to patch clamp paired neurons in the supragranular cortex and to characterise the electrophysiology and the neuroanatomy of the connection between the neurons. Short-term synaptic dynamics will be used as a probe to assess the strength of single-axon connections. The neurons will be filled with biocytin. Triple-label immunofluorescence combined with confocal microscopy will detect biocytin filled neurons, presynaptic boutons and postsynaptic density. Colocalisation of the three labels indicates the site of synapses between the two neurons under study. I will define how the short-term dynamics of excitatory intracortical synapses vary with the period of deprivation and assess whether synaptic number changes contemporaneously. A parallel study will focus on the synaptic dynamics of inhibitory circuitry in supragranular cortex. This will determine whether inhibition is affected by sensory deprivation and help to assess if the balance of excitation and inhibition is altered. Finally, a complementary series of experiments will test the hypotheses that long-term potentiation/depression drive the alterations in synaptic dynamics found at the junction of deprived and spared cortex.