The adult cortex can reorganize in response to various manipulations that affect the activity of inputs to the cortex, and also to behavioral training and other natural stimuli. However, little is known about the cellular and synaptic events that underlie changes in cortical representations, although changes in the balance of excitation and inhibition, or """"""""unmasking"""""""" of previously silent inputs, have been hypothesized to play a role in reorganization. In this proposal, experiments designed to examine possible synaptic and cellular mechanisms underlying cortical reorganizations in adult rat primary somatosensory cortex (S1) are detailed. The experiments make use of a novel in vivo/in vitro preparation, in which the location of the border between the lower jaw and forepaw representations in S2 can be determined and visibly marked in vivo. Then, EPSPs and IPSPs can be recorded in neurons close to the border in vitro in response to stimulation of horizontal connection in layer 2/3. Effects of the border on both EPSPs and IPSPs are observed. Using this preparation, the effects on EPSPs and IPSPs at both original and reorganized borders will be determined for two manipulations that have been shown to cause large changes in S1 representations in vivo. Peripheral lesions have been shown to cause large, rapid reorganizations of S1 representations in vivo. Using this in vivo/in vitro preparation, changes in EPSPs and IPSPs evoked by electrical stimulation of horizontal pathways in layer 2/3 will be assessed at both the original forepaw/lower jaw border and the reorganized border (which will also have been marked in vivo), after denervation of the contralateral forepaw by brachial nerve transection. Intracortical microstimulation (ICMS) can also cause large shifts of representational borders away from the site of ICMS in vivo. A similar ICMS protocol will be used in vitro to induce changes in the location of the previously marked forepaw/lower jaw border. Changes in EPSPs and IPSPs evoked by electrical stimulation of horizontal pathways at and around the original border will then be assessed. These experiments will provide data on the basic synaptic mechanisms that can underlie rapid changes in cortical representations, focusing on changes in the balance of excitation and inhibition. Considering that such changes may underlie recovery from stroke, and that deficits in the control of cortical plasticity may be related to neuropathies from epilepsy to learning disabilities, understanding the cellular mechanisms that might underlie plasticity of cortical assemblies can contribute to the understanding and treatment of neuropathies.
| Hickmott, Peter W; Merzenich, Michael M (2002) Local circuit properties underlying cortical reorganization. J Neurophysiol 88:1288-301 |
| Hickmott, P W; Merzenich, M M (1999) Dendritic bias of neurons in rat somatosensory cortex associated with a functional boundary. J Comp Neurol 409:385-99 |
