Question: 

The primarily undamaged vicinity of a focal lesion in the CNS is often surrounded by an area of neuronal tissue undergoing functional reorganization to compensate the functional loss. In this regard neurons at the border of a focal injury in visual cortex have been shown to express an increased receptive field size in vivo as well as a facilitated long-term potentiation (LTP) in vitro. Here we asked about the cellular mechanisms underlying this functional reorganization.

Methods: 

Chronical focal laser lesions of 1mm in diameter were induced in the visual cortex of anaesthetized rats (P21). After a survival time of two to 7 days acute brain slices were prepared from the visual cortex to study pre- and postsynaptic functiona of pyramidal neurons in layers II/III by use of electrophysiological whole-cell patch clamp recordings.

Results: 

We observed a metaplastic shift from LTD to LTP at glutamatergic synapses from horizontal inputs at the border of the injury. These changes in LTP and LTD were mediated by alterations in function of both, glutamatergic and GABAergic synapses. Recordings of mEPSCs and calculation of the paired-pulse ratio of eEPSCS suggested an increased glutamate release. Furthermore, we observed a functional re- expression of NMDA-receptors located at extra-/presynaptic sites by use recordings with an intracellular application of MK-801. Activity from these non-postsynaptic receptors can boost the excitatory synaptic transmission in the cortical networks. On top,we observed a reduced transmitter release at GABAergic synapses post-lesion, which further supports the lesion-induced facilitation of LTP. Interestingly, homeostatic mechanisms at the postsynaptic site of GABAergic synapses ensured that the oberved metaplastic change of synaptic plasticity, which we believe is a key mechanism for functional reorganization post-injury, is not malformed into hyperexcitability or even epilepsy.

Conclusions: 

The overall strength of GABAergic inhibition in the cortical networks is one critical parameter for a successful functional recovery in the present lesion model. In this regard, future neuropharmacological therapies for patients suffering from a focal brain injury may consider to include agents to modulate the strength of GABAergic inhibition.